SUSPENDED

Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies

Conditions

Locally Advanced Malignant Solid Neoplasm Locally Advanced Unresectable Cholangiocarcinoma Locally Advanced Unresectable Gallbladder Carcinoma Locally Advanced Unresectable Malignant Solid Neoplasm Metastatic Cholangiocarcinoma Metastatic Gallbladder Carcinoma Metastatic Malignant Solid Neoplasm Stage III Gallbladder Cancer AJCC v8 Stage IV Gallbladder Cancer AJCC v8 Unresectable Malignant Solid Neoplasm

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I/II trial studies the best dose and side effects of peposertib and to see how well it works with avelumab and hypofractionated radiation therapy in treating patients with solid tumors and hepatobiliary malignancies that have spread to other places in the body (advanced/metastatic). Peposertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving peposertib in combination with avelumab and hypofractionated radiation therapy may work better than other standard chemotherapy, hormonal, targeted, or immunotherapy medicines available in treating patients with solid tumors and hepatobiliary malignancies.

Official Title

A Phase I/II Study of M3814 and Avelumab in Combination With Hypofractionated Radiation in Patients With Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies

Quick Facts

Study Start:2020-04-07

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:SUSPENDED

Study ID

NCT04068194

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced unresectable solid tumor that has progressed on or after available standard of care therapy or for which no acceptable standard of care therapy exists, or in which the patient declines standard of care therapy (each patient that declines standard of care therapy will be documented in the case report form) * PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on gemcitabine, cisplatin, and durvalumab/pembrolizumab. * Age \>= 18 years * Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with avelumab in patients \< 18 years of age * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) * Patients with at least 1 index lesion to irradiate for whom palliative radiation treatment is indicated (including but not limited to pain and/or symptom control, prevention of disease -related complications, and preservation of organ function). Lung and liver lesions are preferred, though alternate lesions may be considered after discussion with trial principal investigator (PI). Up to 2 lesions may be considered for irradiation provided at least 1 lesion will receive the study treatment of total of 60 Gy and all prescribed irradiation will be completed within the radiation window * Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST) measurable lesion (to be unirradiated) (defined as those accurately measured in at least one dimension, with the longest diameter to be recorded for non-nodal lesions and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph nodes * Patients must be willing to undergo fresh biopsies at baseline (as opposed to using archival tissue), in the event their baseline tissue was obtained \> 12 months prior to study consent and/or they are randomized to the gamma H2AX, pNBS1 and pKAP1 IFA with beta CATN segmentation assay * Absolute neutrophil count (ANC) \>= 1,500/mcL * Platelet count \>= 100,000/mcL * Hemoglobin \>= 9.0 g/dL * Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine clearance (glomerular filtration rate \[GFR\] can be used in place of creatinine or creatinine clearance) \>= 60 mL/min for participants with creatinine levels \> 1.5 x institutional ULN * Calculate serum creatinine clearance using the standard Cockcroft-Gault formula * Serum total bilirubin =\< 1.5 x ULN or direct bilirubin =\< ULN for participants with total bilirubin \> 1.5 x ULN * Patients with known Gilbert disease with serum bilirubin level =\< 3 x ULN are eligible * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN or =\< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases * Albumin \>= 2.8 g/L * International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) =\< 1.5 x ULN * This applies only to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose * Participants must have the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption * Female patients of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The effects of peposertib (M3814) and avelumab on the developing human fetus are unknown and there is the potential for teratogenic or abortifacient effects. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 6 months after completion of peposertib (M3814) and avelumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814) and avelumab, breastfeeding should be discontinued if the mother is treated with peposertib (M3814) and avelumab * Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) and/or family member available will also be eligible	* PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents * PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with the following exceptions: * Patients who have only received previous durvalumab (anti-PD-L1) in combination with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen) are eligible * Patients who have only received previous pembrolizumab (anti-PD-1) in combination with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966 regimen) are eligible * Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 21 days of first planned dose of study therapy (within 14 days for palliative radiation). Previously irradiated lesions may be re-irradiated provided there is disease progression in the irradiated lesion and the prescribed radiation dosage can safely be re- administered * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 1) with the exception of alopecia * Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal disease. Patients with asymptomatic, treated CNS disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy and the following criteria are met: * Radiographic demonstration of clinical stability upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study done \>= 4 weeks from completion of radiotherapy and \>= 2 weeks from discontinuation of corticosteroids * No stereotactic radiation or whole-brain radiation within 28 days prior to randomization * Patients with active autoimmune disease requiring systemic corticosteroids greater than the equivalent of prednisone 10 mg daily including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the following exceptions: * Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible * Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible * Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only who require only low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) are eligible * Patients receiving treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 6 weeks must discontinue these medications prior to starting peposertib (M3814) and avelumab on day 7, with the exception of: * Patients with active autoimmune disease managed with systemic corticosteroids less than the equivalent of prednisone 10 mg daily * Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) * The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension and adrenocortical insufficiency * Patients who have undergone prior solid organ or bone marrow transplant with the exception of patients with prior renal transplant for whom dialysis may be employed in the event of graft rejection * Patients with uncontrolled intercurrent illness (e.g., including but not limited to uncontrolled hypertension \[HTN\] \[systolic blood pressure (BP) \> 150, diastolic BP \> 100\], symptomatic congestive heart failure \[CHF\], unstable angina pectoris, ischemic myocardial infarction \[MI\] within 6 months, cardiac arrhythmia, recent transient ischemic attack \[TIA or cerebrovascular accident (CVA)\]) within 6 months * Patients with serious active infection (e.g. requiring hospitalization and/or intravenous \[IV\] antibiotics) within 4 weeks prior to starting peposertib (M3814) and avelumab, or signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of active systemic infection within 2 weeks prior to starting peposertib (M3814) and avelumab. Patients receiving prophylactic antibiotics are eligible * Patients with known chronic hepatitis B virus (HBV) infection must have an undetectable viral load on suppressive therapy if indicated. Patients with known chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are currently on curative treatment are eligible if they have an undetectable HCV viral load * Patients with known human immunodeficiency virus (HIV) are allowed on study provided they have: * A stable regimen of highly active anti-retroviral therapy (HAART) * No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infection * A CD4 count above 250 cells/mcL * An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based testing * Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Patients with known concurrent malignancy that is expected to require active treatment within two years, or may interfere with the interpretation of the efficacy and safety outcomes of this study in the opinion of the treating investigator. Superficial bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring cytotoxic therapy should not exclude participation in this trial. Patients with chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active chemotherapy and their hematologic, renal and hepatic function meets criteria previously mentioned * Patients with psychiatric illness/social situations that would limit compliance with study requirements * History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) or avelumab * Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting peposertib (M3814) and avelumab are ineligible. Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first peposertib (M3814) dose. Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as judged by the investigator must stop at least 1 day prior to first peposertib (M3814) dose. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. The primary elimination mechanism of avelumab is proteolytic degradation, thus there are no contraindicated medications with respect to avelumab * Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to starting peposertib (M3814) and avelumab. These must be discontinued \>= 5 days prior to starting peposertib (M3814) and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers are allowed provided they are taken at least 2 hours after peposertib (M3814) dose * Patients receiving sorivudine or any chemically related analogues (such as brivudine) and not able to discontinue prior to starting peposertib (M3814) and avelumab are excluded * Pregnant and lactating women are excluded from this study because peposertib (M3814) and avelumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814) and avelumab, breastfeeding should be discontinued if the mother is treated with peposertib (M3814) and avelumab * Patients who have received live vaccination within 30 days before starting peposertib (M3814) and avelumab

Inclusion Criteria

Exclusion Criteria

* PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced unresectable solid tumor that has progressed on or after available standard of care therapy or for which no acceptable standard of care therapy exists, or in which the patient declines standard of care therapy (each patient that declines standard of care therapy will be documented in the case report form)
* PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on gemcitabine, cisplatin, and durvalumab/pembrolizumab.
* Age \>= 18 years
* Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with avelumab in patients \< 18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Patients with at least 1 index lesion to irradiate for whom palliative radiation treatment is indicated (including but not limited to pain and/or symptom control, prevention of disease -related complications, and preservation of organ function). Lung and liver lesions are preferred, though alternate lesions may be considered after discussion with trial principal investigator (PI). Up to 2 lesions may be considered for irradiation provided at least 1 lesion will receive the study treatment of total of 60 Gy and all prescribed irradiation will be completed within the radiation window
* Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST) measurable lesion (to be unirradiated) (defined as those accurately measured in at least one dimension, with the longest diameter to be recorded for non-nodal lesions and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph nodes
* Patients must be willing to undergo fresh biopsies at baseline (as opposed to using archival tissue), in the event their baseline tissue was obtained \> 12 months prior to study consent and/or they are randomized to the gamma H2AX, pNBS1 and pKAP1 IFA with beta CATN segmentation assay
* Absolute neutrophil count (ANC) \>= 1,500/mcL
* Platelet count \>= 100,000/mcL
* Hemoglobin \>= 9.0 g/dL
* Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine clearance (glomerular filtration rate \[GFR\] can be used in place of creatinine or creatinine clearance) \>= 60 mL/min for participants with creatinine levels \> 1.5 x institutional ULN
* Calculate serum creatinine clearance using the standard Cockcroft-Gault formula
* Serum total bilirubin =\< 1.5 x ULN or direct bilirubin =\< ULN for participants with total bilirubin \> 1.5 x ULN
* Patients with known Gilbert disease with serum bilirubin level =\< 3 x ULN are eligible
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN or =\< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases
* Albumin \>= 2.8 g/L
* International normalized ratio (INR) or prothrombin time (PT) or activated partial thromboplastin time (aPTT) =\< 1.5 x ULN
* This applies only to patients not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose
* Participants must have the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption
* Female patients of childbearing potential must have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The effects of peposertib (M3814) and avelumab on the developing human fetus are unknown and there is the potential for teratogenic or abortifacient effects. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 6 months after completion of peposertib (M3814) and avelumab administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814) and avelumab, breastfeeding should be discontinued if the mother is treated with peposertib (M3814) and avelumab
* Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) and/or family member available will also be eligible

* PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents
* PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with the following exceptions:
* Patients who have only received previous durvalumab (anti-PD-L1) in combination with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen) are eligible
* Patients who have only received previous pembrolizumab (anti-PD-1) in combination with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966 regimen) are eligible
* Patients who have had chemotherapy, definitive radiation, biological cancer therapy, or investigational agent/device within 21 days of first planned dose of study therapy (within 14 days for palliative radiation). Previously irradiated lesions may be re-irradiated provided there is disease progression in the irradiated lesion and the prescribed radiation dosage can safely be re- administered
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 1) with the exception of alopecia
* Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal disease. Patients with asymptomatic, treated CNS disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy and the following criteria are met:
* Radiographic demonstration of clinical stability upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study done \>= 4 weeks from completion of radiotherapy and \>= 2 weeks from discontinuation of corticosteroids
* No stereotactic radiation or whole-brain radiation within 28 days prior to randomization
* Patients with active autoimmune disease requiring systemic corticosteroids greater than the equivalent of prednisone 10 mg daily including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the following exceptions:
* Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
* Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only who require only low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) are eligible
* Patients receiving treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 6 weeks must discontinue these medications prior to starting peposertib (M3814) and avelumab on day 7, with the exception of:
* Patients with active autoimmune disease managed with systemic corticosteroids less than the equivalent of prednisone 10 mg daily
* Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea)
* The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension and adrenocortical insufficiency
* Patients who have undergone prior solid organ or bone marrow transplant with the exception of patients with prior renal transplant for whom dialysis may be employed in the event of graft rejection
* Patients with uncontrolled intercurrent illness (e.g., including but not limited to uncontrolled hypertension \[HTN\] \[systolic blood pressure (BP) \> 150, diastolic BP \> 100\], symptomatic congestive heart failure \[CHF\], unstable angina pectoris, ischemic myocardial infarction \[MI\] within 6 months, cardiac arrhythmia, recent transient ischemic attack \[TIA or cerebrovascular accident (CVA)\]) within 6 months
* Patients with serious active infection (e.g. requiring hospitalization and/or intravenous \[IV\] antibiotics) within 4 weeks prior to starting peposertib (M3814) and avelumab, or signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of active systemic infection within 2 weeks prior to starting peposertib (M3814) and avelumab. Patients receiving prophylactic antibiotics are eligible
* Patients with known chronic hepatitis B virus (HBV) infection must have an undetectable viral load on suppressive therapy if indicated. Patients with known chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are currently on curative treatment are eligible if they have an undetectable HCV viral load
* Patients with known human immunodeficiency virus (HIV) are allowed on study provided they have:
* A stable regimen of highly active anti-retroviral therapy (HAART)
* No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infection
* A CD4 count above 250 cells/mcL
* An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based testing
* Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Patients with known concurrent malignancy that is expected to require active treatment within two years, or may interfere with the interpretation of the efficacy and safety outcomes of this study in the opinion of the treating investigator. Superficial bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring cytotoxic therapy should not exclude participation in this trial. Patients with chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active chemotherapy and their hematologic, renal and hepatic function meets criteria previously mentioned
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to peposertib (M3814) or avelumab
* Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting peposertib (M3814) and avelumab are ineligible. Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first peposertib (M3814) dose. Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as judged by the investigator must stop at least 1 day prior to first peposertib (M3814) dose. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. The primary elimination mechanism of avelumab is proteolytic degradation, thus there are no contraindicated medications with respect to avelumab
* Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to starting peposertib (M3814) and avelumab. These must be discontinued \>= 5 days prior to starting peposertib (M3814) and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers are allowed provided they are taken at least 2 hours after peposertib (M3814) dose
* Patients receiving sorivudine or any chemically related analogues (such as brivudine) and not able to discontinue prior to starting peposertib (M3814) and avelumab are excluded
* Pregnant and lactating women are excluded from this study because peposertib (M3814) and avelumab are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814) and avelumab, breastfeeding should be discontinued if the mother is treated with peposertib (M3814) and avelumab
* Patients who have received live vaccination within 30 days before starting peposertib (M3814) and avelumab

Contacts and Locations

Principal Investigator

Kristen R Spencer

PRINCIPAL_INVESTIGATOR

Laura and Isaac Perlmutter Cancer Center at NYU

Study Locations (Sites)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612

United States

UC San Diego Moores Cancer Center

La Jolla, California, 92093

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045

United States

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418

United States

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, 06824

United States

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, 06033

United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, 06830

United States

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437

United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105

United States

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510

United States

Yale University

New Haven, Connecticut, 06520

United States

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473

United States

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, 06902

United States

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790

United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611

United States

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, 06708

United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, 06385

United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007

United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016

United States

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324

United States

Emory University Hospital Midtown

Atlanta, Georgia, 30308

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342

United States

Northwestern University

Chicago, Illinois, 60611

United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903

United States

Bellevue Hospital Center

New York, New York, 10016

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016

United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032

United States

NYP/Weill Cornell Medical Center

New York, New York, 10065

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

United States

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, 02891

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298

United States

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718

United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Kristen R Spencer, PRINCIPAL_INVESTIGATOR, Laura and Isaac Perlmutter Cancer Center at NYU

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-04-07

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2020-04-07

Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

Locally Advanced Malignant Solid Neoplasm
Locally Advanced Unresectable Cholangiocarcinoma
Locally Advanced Unresectable Gallbladder Carcinoma
Locally Advanced Unresectable Malignant Solid Neoplasm
Metastatic Cholangiocarcinoma
Metastatic Gallbladder Carcinoma
Metastatic Malignant Solid Neoplasm
Stage III Gallbladder Cancer AJCC v8
Stage IV Gallbladder Cancer AJCC v8
Unresectable Malignant Solid Neoplasm