RECRUITING

Dosing Study of Radiation Combined With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Cancer

Conditions

Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Head and Neck Carcinoma Head and Neck Cancer Stage IV Head and Neck Cancers - Throat throat cancer HNSCC treatment

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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

The purpose of this study is to evaluate the safety, tolerability and maximum tolerated dose of tislelizumab in combination with pamiparib plus chemoradiotherapy (chemotherapy and radiation) in individuals with recurrent head and neck cancer, which means that the person's cancer has come back after treatment. Participation in the study should last for about 15 months while participants receive tislelizumab and chemoradiotherapy with pamiparib. Afterwards, they will return to the clinic for follow up every 4 months for 2 years, every 6 month for the next 2 years, and then once a year for the rest of their life.

Official Title

A Phase I Trial of Re-Irradiation With Concurrent Chemotherapy in Combination With Tislelizumab and Pamiparib in Patients With Previously Treated Head and Neck Squamous Cell Carcinoma

Quick Facts

Study Start:2023-03-07

Study Completion:2026-01-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05526924

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
* Clinically documented recurrent head and neck cancer requiring regional therapy. * Human papillomavirus (HPV) testing for oropharynx primary tumors by p16 immunohistochemistry (IHC) positivity * Availability of more than (or equal to) 10 unstained 5 micron slides (to be provided to Human Tissue Resource Center at the University of Chicago). Subjects who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study. * Recurrent or second primary, previously irradiated head and neck squamous cell carcinoma without clinically measurably distant metastatic disease, or low volume oligometastatic disease amenable to Stereotactic Body Radiation Therapy (SBRT) or other curative-intent therapy (e.g. surgery, radiation frequency ablation therapy) * Prior radiation therapy completed in 4 months (or longer) , and/or chemotherapy, immunotherapy, or targeted therapy completed 1 month (or earlier) before study entry, and patient should have recovered from any adverse effects. * Prior programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibition is permitted. * Prior chemotherapy is permitted. * Patients who undergo surgical salvage therapy with positive margin or extranodal extension or other high-risk patients determined during multidisciplinary tumor board who are eligible for adjuvant re-irradiation therapy are eligible. * 18 years of age and older. * Eastern Cooperative Oncology Group performance status of one or less. * Life expectancy of greater than 12 weeks. * Negative serum or urine pregnancy test at screening for patients of childbearing potential. * Patients must have normal organ and marrow functions as defined by lab values that will be confirmed by the study doctor. * Age, Sex, and Reproductive Status: 1. Women of childbearing potential (WOCBP=premenopausal woman capable of becoming pregnant) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug. 2. Women must not be breastfeeding. 3. WOCBP must agree to follow instructions for highly effective method(s) of contraception for the duration of treatment and for 180 days (6 months) after the last dose of study drug(s). 4. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 180 days (6 months) after the last dose of study drug(s). 5. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. Females must still undergo pregnancy testing as described in this section. * At a minimum subjects must agree to the use of one method of highly effective contraception as listed in Appendix D. In addition, male subjects are expected to use a condom as noted in Appendix D. The effects of tislelizumab and pamiparib on the developing human fetus are unknown. For this reason and because monoclonal antibodies and PARP inhibitor agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of pamiparib and tislelizumab administration. * Ability to understand and the willingness to sign a written informed consent document.	* • Previously untreated patients with locoregional-only disease are not eligible. * Patients who have had chemotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. * Patients may not be receiving any other investigational agents. * History of allergic reactions attributed to compounds of similar chemical composition or excipients used in the study. * Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s). * Note: Patients who are currently or have recently been on any of the following corticosteroid regimens are not excluded: * Adrenal replacement corticosteroid (dose ≤ 10 mg daily of prednisone or equivalent) * Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption * Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a nonautoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen) * Has hypersensitivity to tislelizumab, pamiparib, or any other drug used in this protocol. * Has a known history of active tuberculosis (Bacillus Tuberculosis infection) * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy), or prior history of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). * Has active autoimmune disease that has required systemic treatment in the past year (i.e. with use of steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment. * Has known history of, or any evidence of active interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases. * Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). However, if eradicated subject is eligible. * Has received a live vaccine within 28 days of planned start of study therapy. * Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * Patients receiving any medications or substances that are known to be strong CYP3A inducers (eg. avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampin/ rifampicin) are ineligible. Patients receiving herbal remedies/medicines such as St. John's Wort (Hypericum perforatum) are also ineligible. See Sections 5.5.2 and 5.5.3 for prohibited medications on study. * Pregnant women are excluded from this study because pamiparib is a PARP inhibitor and tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody agent 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 pamiparib and tislelizumab, breastfeeding should be discontinued if the mother is treated with pamiparib and tislelizumab. * HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pamiparib and tislelizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. * Disease/procedure significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastrointestinal perforation or fistulae. Note: Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (assuming no drug interaction potential).

Inclusion Criteria

Exclusion Criteria

* Clinically documented recurrent head and neck cancer requiring regional therapy.
* Human papillomavirus (HPV) testing for oropharynx primary tumors by p16 immunohistochemistry (IHC) positivity
* Availability of more than (or equal to) 10 unstained 5 micron slides (to be provided to Human Tissue Resource Center at the University of Chicago). Subjects who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study.
* Recurrent or second primary, previously irradiated head and neck squamous cell carcinoma without clinically measurably distant metastatic disease, or low volume oligometastatic disease amenable to Stereotactic Body Radiation Therapy (SBRT) or other curative-intent therapy (e.g. surgery, radiation frequency ablation therapy)
* Prior radiation therapy completed in 4 months (or longer) , and/or chemotherapy, immunotherapy, or targeted therapy completed 1 month (or earlier) before study entry, and patient should have recovered from any adverse effects.
* Prior programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibition is permitted.
* Prior chemotherapy is permitted.
* Patients who undergo surgical salvage therapy with positive margin or extranodal extension or other high-risk patients determined during multidisciplinary tumor board who are eligible for adjuvant re-irradiation therapy are eligible.
* 18 years of age and older.
* Eastern Cooperative Oncology Group performance status of one or less.
* Life expectancy of greater than 12 weeks.
* Negative serum or urine pregnancy test at screening for patients of childbearing potential.
* Patients must have normal organ and marrow functions as defined by lab values that will be confirmed by the study doctor.
* Age, Sex, and Reproductive Status:
1. Women of childbearing potential (WOCBP=premenopausal woman capable of becoming pregnant) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
2. Women must not be breastfeeding.
3. WOCBP must agree to follow instructions for highly effective method(s) of contraception for the duration of treatment and for 180 days (6 months) after the last dose of study drug(s).
4. Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 180 days (6 months) after the last dose of study drug(s).
5. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. Females must still undergo pregnancy testing as described in this section.
* At a minimum subjects must agree to the use of one method of highly effective contraception as listed in Appendix D. In addition, male subjects are expected to use a condom as noted in Appendix D. The effects of tislelizumab and pamiparib on the developing human fetus are unknown. For this reason and because monoclonal antibodies and PARP inhibitor agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of pamiparib and tislelizumab administration.
* Ability to understand and the willingness to sign a written informed consent document.

* • Previously untreated patients with locoregional-only disease are not eligible.
* Patients who have had chemotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
* Patients may not be receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical composition or excipients used in the study.
* Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before the first dose of study drug(s).
* Note: Patients who are currently or have recently been on any of the following corticosteroid regimens are not excluded:
* Adrenal replacement corticosteroid (dose ≤ 10 mg daily of prednisone or equivalent)
* Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption
* Short course (≤ 7 days) of corticosteroid prescribed prophylactically (e.g., for contrast dye allergy) or for the treatment of a nonautoimmune condition (e.g., delayed-type hypersensitivity reaction caused by contact allergen)
* Has hypersensitivity to tislelizumab, pamiparib, or any other drug used in this protocol.
* Has a known history of active tuberculosis (Bacillus Tuberculosis infection)
* Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or any tumors that are not likely to influence live expectancy in the subsequent 3 years without active treatment (e.g. low grade prostate cancer in absence of therapy), or prior history of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS).
* Has active autoimmune disease that has required systemic treatment in the past year (i.e. with use of steroids or immunosuppressive drugs). Replacement therapy e.g. levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment.
* Has known history of, or any evidence of active interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis, or acute lung diseases.
* Has a history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
* Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). However, if eradicated subject is eligible.
* Has received a live vaccine within 28 days of planned start of study therapy.
* Uncontrolled intercurrent illness including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* Patients receiving any medications or substances that are known to be strong CYP3A inducers (eg. avasimibe, carbamazepine, mitotane, phenobarbital, phenytoin, rifabutin, rifampin/ rifampicin) are ineligible. Patients receiving herbal remedies/medicines such as St. John's Wort (Hypericum perforatum) are also ineligible. See Sections 5.5.2 and 5.5.3 for prohibited medications on study.
* Pregnant women are excluded from this study because pamiparib is a PARP inhibitor and tislelizumab is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody agent 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 pamiparib and tislelizumab, breastfeeding should be discontinued if the mother is treated with pamiparib and tislelizumab.
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pamiparib and tislelizumab. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
* Disease/procedure significantly affecting gastrointestinal function, such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastrointestinal perforation or fistulae. Note: Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed (assuming no drug interaction potential).

Contacts and Locations

Study Contact

Cancer Trial Intake

CONTACT

1-855-702-8222

cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator

Ari Rosenberg, MD

PRINCIPAL_INVESTIGATOR

University of Chicago

Study Locations (Sites)

The University of Chicago

Chicago, Illinois, 60637

United States

Collaborators and Investigators

Sponsor: University of Chicago

Ari Rosenberg, MD, PRINCIPAL_INVESTIGATOR, University of Chicago

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 Date2023-03-07

Study Completion Date2026-01-01

Study Record Updates

Study Start Date2023-03-07

Study Completion Date2026-01-01

Terms related to this study

Keywords Provided by Researchers

head and neck cancer
head and neck carcinoma
Head and Neck Squamous Cell Carcinoma
throat cancer
HNSCC treatment

Additional Relevant MeSH Terms

Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Head and Neck Carcinoma
Head and Neck Cancer Stage IV
Head and Neck Cancers - Throat