RECRUITING

Radiation Medication (Radium-223 Dichloride) Versus Radium-223 Dichloride Plus Radiation Enhancing Medication (M3814) Versus Radium-223 Dichloride Plus M3814 Plus Avelumab (a Type of Immunotherapy) for Advanced Prostate Cancer Not Responsive to Hormonal Therapy

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Conditions

Metastatic Castration-Resistant Prostate CarcinomaMetastatic Malignant Neoplasm in the BoneMetastatic Malignant Neoplasm in the Lymph NodesStage IV Prostate Cancer AJCC v8

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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 of M3814 when given together with radium-223 dichloride or with radium-223 dichloride and avelumab and to see how well they work in treating patients with castrate-resistant prostate cancer that had spread to other places in the body (metastatic). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as radium-223 dichloride, may carry radiation directly to tumor cells and not harm normal cells. 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. This study is being done to find out the better treatment between radium-223 dichloride alone, radium-223 dichloride in combination with M3814, or radium-223 dichloride in combination with both M3814 and avelumab, to lower the chance of prostate cancer growing or spreading in the bone, and if this approach is better or worse than the usual approach for advanced prostate cancer not responsive to hormonal therapy.

Official Title

A Phase I and Randomized Phase II Trial of Radium-223 Dichloride, M3814, &Amp; Avelumab in Advanced Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

Quick Facts

Study Start:2020-10-14
Study Completion:2025-01-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04071236

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:MALE
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * PHASE 1: Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
  2. * PHASE 2: ECOG performance status =\< 2 (Karnofsky \>= 60%)
  3. * Unless a patient has had orchiectomy by surgery, the patient is expected to be on antiandrogen therapy (ADT) for "medical castration". ADT needs to be maintained throughout the study. Testosterone level should be checked, and kept consistently lower than 50 ng/dL, similar to that obtained with bilateral orchiectomy
  4. * Progressive castration-resistant prostate cancer with two or more skeletal metastases identified by 99mTC bone scintigraphy. One or more lymph node metastases allowed, but not mandatory. Lymph node metastases in each individually must measure less than 3 cm in the longest dimension. Visible visceral organ metastases are not allowed. A diagnosis of prostate cancer must have been histologically confirmed at any time point
  5. * Baseline prostatic specific antigen (PSA) level of 1 ng/mL or higher with evidence of progressively increasing PSA values (two consecutive increases over the previous reference value)
  6. * Progression after at least one of the following: abiraterone, enzalutamide, apalutamide, darolutamide, or taxane chemotherapy (docetaxel, cabazitaxel). There is no maximum number of prior therapies. Prior immunotherapies (for example, Sipuleucel-T or pembrolizumab) do not exclude the patient from participation
  7. * Age \>= 18 years. Castrate-resistant prostate cancer (CRPC) affects older adults and is rarely encountered in children and adolescents
  8. * Life expectancy \>= 6 months
  9. * Albumin \> 2.5 mg/dL
  10. * Hemoglobin \> 9 g/dL
  11. * Leukocytes \>= 3,000/mcL
  12. * Absolute neutrophil count \>= 1,500/mcL
  13. * Platelets \>= 100,000/mcL
  14. * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (with the exception of \< 3 mg/dL for patients with Gilbert's disease)
  15. * Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
  16. * Creatinine =\< 1.5 x institutional ULN OR
  17. * Glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2
  18. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
  19. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
  20. * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
  21. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  22. * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional classification. To be eligible for this trial, patients should be class 2B or better
  23. * Concomitant use of physiologic corticosteroids is allowed
  24. * Concomitant use of bisphosphonates is allowed (use of bone health agents is mandatory - either denosumab \[preferred\] or bisphosphonates)
  25. * The effects of radium-223 dichloride, M3814, and avelumab on the developing human fetus are unknown. 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 Radium-223 dichloride, M3814, and avelumab administration
  26. * Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
  27. * Patients must be able to swallow orally administered medication
  28. * Patients with asymptomatic, treated brain metastases are permitted if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging \[MRI\] or CT scan) during the screening period
  1. * Active autoimmune conditions or patients on chronic immunosuppression due to underlying autoimmune condition
  2. * Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
  3. * Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
  4. * Patients who are receiving any other investigational agents
  5. * Patients who have had previous hemibody external radiation
  6. * Patients who have had systemic radiotherapy with radioisotopes
  7. * Patients who have imminent/established spinal cord compression, pathological fracture in weight bearing bones or bone lesion with soft tissue component unless treated as appropriate with radiation and/or surgery before starting on trial
  8. * Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to radium-223 dichloride, M3814, or avelumab
  9. * Patients unable to discontinue medications or substances that are potent inhibitors, inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to study treatment are ineligible.
  10. * Medications or substances that are strong inhibitors of CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
  11. * Medications or substances that are strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the first M3814 dose.
  12. * Drugs mainly metabolized by CYP3A with a narrow therapeutic index (as judged by the Investigator or authorized designee) must be discontinued at least 1 day prior to first M3814 dose.
  13. * Note: 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.
  14. * Radium-223 dichloride should not be given concurrently with abiraterone plus prednisone/prednisolone
  15. * Patients with uncontrolled intercurrent illness
  16. * Patients with psychiatric illness/social situations that would limit compliance with study requirements
  17. * Patients must not have an active infection requiring systemic treatment
  18. * Patients must not use immunosuppressive medication =\< 7 days of registration, EXCEPT for the following:
  19. * Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
  20. * Systemic corticosteroids at physiologic doses =\< 10 mg/day of prednisone or equivalent
  21. * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  22. * Patients who cannot discontinue concomitant H2 blockers or proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued \>= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate
  23. * Patients receiving sorivudine or any chemically related analogues (such as brivudine) are excluded
  24. * Patients with a known history or present osteonecrosis of the jaw

Contacts and Locations

Principal Investigator

Hiram Gay
PRINCIPAL_INVESTIGATOR
Yale University Cancer Center LAO

Study Locations (Sites)

City of Hope Comprehensive Cancer Center
Duarte, California, 91010
United States
Los Angeles General Medical Center
Los Angeles, California, 90033
United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
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
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
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116
United States
Washington University School of Medicine
Saint Louis, Missouri, 63110
United States
Siteman Cancer Center-South County
Saint Louis, Missouri, 63129
United States
Siteman Cancer Center at Saint Peters Hospital
Saint Peters, Missouri, 63376
United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

  • Hiram Gay, PRINCIPAL_INVESTIGATOR, Yale University Cancer Center LAO

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 Date2020-10-14
Study Completion Date2025-01-31

Study Record Updates

Study Start Date2020-10-14
Study Completion Date2025-01-31

Terms related to this study

Additional Relevant MeSH Terms

  • Metastatic Castration-Resistant Prostate Carcinoma
  • Metastatic Malignant Neoplasm in the Bone
  • Metastatic Malignant Neoplasm in the Lymph Nodes
  • Stage IV Prostate Cancer AJCC v8