Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations

NCT ID: NCT03570619

Last Updated: 2025-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-14
• Study Completion Date: 2024-03-26

Brief Summary

This study will attempt to determine the efficacy of checkpoint inhibitor immunotherapy with nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy in patients with metastatic prostate cancer and other tumor solid tumor histologies harboring loss of CDK12 function as well as monotherapy nivolumab treatment in patient with metastatic prostate cancer harboring loss of CDK12 function.

Detailed Description

This study investigates the efficacy of checkpoint inhibitor immunotherapy in patients with metastatic cancer with CDK12 mutations. The study includes three cohorts: Cohort A consists of metastatic prostate cancer patients being treated with combination nivolumab and ipilimumab treatment followed by monotherapy nivolumab treatment. Cohort B consists of other solid tumor patients being treated with combination nivolumab and ipilimumab treatment followed by monotherapy nivolumab treatment. As of an amendment approved 03FEB2021 a third cohort was added, Cohort C, which consists of metastatic prostate cancer patients being treated with monotherapy nivolumab treatment.

As of an amendment approved 21JUN2020 the maximum duration of treatment, as well as the anticipated timing for some of the studies outcome measures, were updated from 52 weeks to 104 weeks.

Conditions

Metastatic Castration Resistant Prostate Cancer; Metastatic Cancer; Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Metastatic CRPC

Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort A.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Patients in arm Metastatic CRPC will receive therapy with monotherapy nivolumab therapy at flat dose 480 mg IV every 4 weeks for up to 104 weeks of total therapy.

Ipilimumab

Intervention Type: DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Solid Tumors (non-prostate)

Patients with all other metastatic subtypes will be enrolled in cohort B

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Patients in arm Metastatic CRPC will receive therapy with monotherapy nivolumab therapy at flat dose 480 mg IV every 4 weeks for up to 104 weeks of total therapy.

Ipilimumab

Intervention Type: DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Metastatic CRPC with Monotherapy

Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort C once enrollment to cohort A has been completed.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Patients in arm Metastatic CRPC will receive therapy with monotherapy nivolumab therapy at flat dose 480 mg IV every 4 weeks for up to 104 weeks of total therapy.

Interventions

Nivolumab

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Patients in arm Metastatic CRPC will receive therapy with monotherapy nivolumab therapy at flat dose 480 mg IV every 4 weeks for up to 104 weeks of total therapy.

Intervention Type: DRUG

Ipilimumab

Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Be ≥18 years of age as of date of signing informed consent.
• Be willing and able to provide written informed consent for the study.
• ECOG Performance Status of 0, 1 or 2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.
• Subjects must have a histologic or cytologic diagnosis of metastatic adenocarcinoma of the prostate without small cell histology OR another type of metastatic carcinoma.
• All subjects, regardless of cancer type, must have a documented CDK12 aberration in tumor tissue.
• Subjects with prostate cancer must have documented prostate cancer progression within six months prior to screening with PSA progression defined as a minimum of three rising PSA levels ≥ 1; 1 week between each assessment with a baseline PSA value at screening of ≥ 2 ng/mL.
• Subjects with prostate cancer must have ongoing androgen deprivation with total serum testosterone < 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)). If the subject is currently being treated with LHRH agonists (subjects who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to registration. This treatment must be continued throughout the study.
• Subjects with non-prostate histologies must have RECIST 1.1-measurable cancer on computed tomography (CT) or magnetic resonance imaging (MRI) scans.
• Subjects must have recovered to baseline or ≤ grade 1 toxicities related to any prior treatments unless AE(s) are clinically non-significant and/or stable.
• Patients must be ≥ 2 weeks from most recent systemic therapy or most recent radiation therapy.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 28 days prior to registration.
• Female and male subjects of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 5 months (for women) and 7 months (for men) after the last dose of study therapy.
• Adequate organ and marrow function

Exclusion Criteria

• Prior treatment with anti-PD-1/PD-L1 and anti-CTLA-4 is NOT allowed. Prior intravesical BCG therapy is allowed.
• Treatment with any investigational agent or on an interventional clinical trial within 28 days prior to registration.
• Prior or concurrent malignancy except for: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized or locally advanced prostate cancer definitively treated without recurrence or with biochemical recurrence only, or any other cancer fully treated or from which the subject has been disease-free for at least 2 years.
• Autoimmune diseases such as rheumatoid arthritis. Vitiligo, mild psoriasis (topical therapy only) or hypothyroidism are allowed.
• Need for systemic corticosteroids >10mg prednisone daily or equivalent alternative steroid (except physiologic dose for adrenal replacement therapy) or other immunosuppressive agents (such as cyclosporine or methotrexate) Topical and inhaled corticosteroids are allowed if medically needed.
• Any history of organ allografts
• Any history of HIV, hepatitis B or hepatitis C infection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ajjai Alva, MD

Role: PRINCIPAL_INVESTIGATOR

Rogel Cancer Center

Locations

University of California San Diego, Moores Cancer Center

San Diego, California, United States

University of California San Francisco/Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

H. Lee. Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Siteman Cancer Center at Washington University

St Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HUM00145104

Identifier Type: OTHER

Identifier Source: secondary_id

UMCC 2018.050

Identifier Type: -

Identifier Source: org_study_id