Clinical Trials /

Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations

NCT03570619

Description:

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 harboring loss of CDK12 function.

Related Conditions:
  • Malignant Solid Tumor
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
  • Official Title: IMPACT: Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2018.050
  • SECONDARY ID: HUM00145104
  • NCT ID: NCT03570619

Conditions

  • Metastatic Castration Resistant Prostate Cancer
  • Metastatic Cancer

Interventions

DrugSynonymsArms
NivolumabMetastatic CRPC
IpilimumabMetastatic CRPC

Purpose

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 harboring loss of CDK12 function.

Trial Arms

NameTypeDescriptionInterventions
Metastatic CRPCExperimentalPatients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort A.
  • Nivolumab
  • Ipilimumab
Solid Tumors (non-prostate)ExperimentalPatients with all other metastatic subtypes will be enrolled in cohort B
  • Nivolumab
  • Ipilimumab

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The proportion of patients with CDK12 loss of function metastatic CRPC (Cohort A) that respond to treatment.
Time Frame:Up to 24 months post treatment
Safety Issue:
Description:The primary objective is overall response rate (ORR) of patients with metastatic CRPC. Response will be defined as a 50% decline in PSA (prostate specific antigen) from baseline as determined by PCWG3 criteria.

Secondary Outcome Measures

Measure:The proportion of patients that respond to treatment in Cohort B.
Time Frame:Up to 52 weeks after start of therapy
Safety Issue:
Description:Overall response will be defined as patients that achieve either a partial response or complete response using RECIST 1.1 criteria. Complete response (CR) is defined as disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.
Measure:Radiographic progression free survival time (rPFS)
Time Frame:Up to 52 weeks after start of therapy
Safety Issue:
Description:Radiographic progression-free survival (rPFS) is defined as the duration of time from start of treatment to time of radiographic progression. Progression is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions.
Measure:Progression free survival time (PFS)
Time Frame:Up to 24 months post treatment
Safety Issue:
Description:Progression is defined as the duration of time from start of treatment to time of progression. Progression is defined as: Either, Radiographic progression: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions OR, PSA Progression: For rising PSA after an initial decline from baseline, the PSA is recorded from the start of therapy to first PSA increase that is ≥ 25% and ≥ 2ng/mL above the nadir, which is confirmed by a second value 4 or more weeks later, confirming a rising trend. If there is no initial decline from baseline, PSA progression is defined as ≥ 25% increase and ≥ 2 ng/mL increase from baseline beyond 12 weeks.
Measure:Duration of Therapy (DOT)
Time Frame:Up to 52 weeks after start of therapy
Safety Issue:
Description:
Measure:Time to Progression (TTP)
Time Frame:Up to 24 months post treatment
Safety Issue:
Description:Progression is defined as the duration of time from start of treatment to time of progression. Progression is defined as: Either, Radiographic progression: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions OR, PSA Progression: For rising PSA after an initial decline from baseline, the PSA is recorded from the start of therapy to first PSA increase that is ≥ 25% and ≥ 2ng/mL above the nadir, which is confirmed by a second value 4 or more weeks later, confirming a rising trend. If there is no initial decline from baseline, PSA progression is defined as ≥ 25% increase and ≥ 2 ng/mL increase from baseline beyond 12 weeks.
Measure:Overall survival Time
Time Frame:Up to 24 months post treatment
Safety Issue:
Description:
Measure:PSA progression free survival time
Time Frame:Up to 24 months post treatment
Safety Issue:
Description:PSA Progression: For rising PSA after an initial decline from baseline, the PSA is recorded from the start of therapy to first PSA increase that is ≥ 25% and ≥ 2ng/mL above the nadir, which is confirmed by a second value 4 or more weeks later, confirming a rising trend. If there is no initial decline from baseline, PSA progression is defined as ≥ 25% increase and ≥ 2 ng/mL increase from baseline beyond 12 weeks.
Measure:Time to PSA progression
Time Frame:Up to 24 months post treatment
Safety Issue:
Description:PSA Progression: For rising PSA after an initial decline from baseline, the PSA is recorded from the start of therapy to first PSA increase that is ≥ 25% and ≥ 2ng/mL above the nadir, which is confirmed by a second value 4 or more weeks later, confirming a rising trend. If there is no initial decline from baseline, PSA progression is defined as ≥ 25% increase and ≥ 2 ng/mL increase from baseline beyond 12 weeks.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Michigan Cancer Center

Trial Keywords

  • Metastatic Cancer
  • Metastatic Castration Resistant Prostate Cancer
  • mCRPC
  • Immunotherapy
  • CDK12

Last Updated