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Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations (IMPACT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03570619
Recruitment Status : Recruiting
First Posted : June 27, 2018
Last Update Posted : March 4, 2020
Sponsor:
Collaborators:
Memorial Sloan Kettering Cancer Center
University of California, San Francisco
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Tracking Information
First Submitted Date  ICMJE June 15, 2018
First Posted Date  ICMJE June 27, 2018
Last Update Posted Date March 4, 2020
Actual Study Start Date  ICMJE December 14, 2018
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2018)
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 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • The proportion of patients that respond to treatment in Cohort B. [ Time Frame: Up to 52 weeks after start of therapy ]
    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.
  • Radiographic progression free survival time (rPFS) [ Time Frame: Up to 52 weeks after start of therapy ]
    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.
  • Progression free survival time (PFS) [ Time Frame: Up to 24 months post treatment ]
    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.
  • Duration of Therapy (DOT) [ Time Frame: Up to 52 weeks after start of therapy ]
    Defined by the time interval from the start of treatment to the day of permanent discontinuation of treatment (including death).
  • Time to Progression (TTP) [ Time Frame: Up to 24 months post treatment ]
    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.
  • Overall survival Time [ Time Frame: Up to 24 months post treatment ]
    Defined as the time from the start of treatment until death from any cause. Patients alive or lost to follow-up at the time of analysis will be censored at their last date of follow-up.
  • PSA progression free survival time [ Time Frame: Up to 24 months post treatment ]
    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.
  • Time to PSA progression [ Time Frame: Up to 24 months post treatment ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2018)
  • The proportion of patients that respond to treatment in Cohort B. [ Time Frame: Up to 52 weeks after start of therapy ]
    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.
  • Radiographic progression free survival time (rPFS) [ Time Frame: Up to 52 weeks after start of therapy ]
    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.
  • Progression free survival time (PFS) [ Time Frame: Up to 24 months post treatment ]
    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.
  • Duration of Therapy (DOT) [ Time Frame: Up to 52 weeks after start of therapy ]
  • Time to Progression (TTP) [ Time Frame: Up to 24 months post treatment ]
    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.
  • Overall survival Time [ Time Frame: Up to 24 months post treatment ]
  • PSA progression free survival time [ Time Frame: Up to 24 months post treatment ]
    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.
  • Time to PSA progression [ Time Frame: Up to 24 months post treatment ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
Official Title  ICMJE IMPACT: Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
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 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 two cohorts of patient groups: castration resistant metastatic prostate carcinoma and other solid tumor histologies. Both cohorts receive the same treatment with the combination of nivolumab and ipilimumab followed by nivolumab.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Castration Resistant Prostate Cancer
  • Metastatic Cancer
Intervention  ICMJE
  • Drug: Nivolumab
    All patients 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 52 weeks of total therapy.
  • Drug: Ipilimumab
    All patients 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 52 weeks of total therapy.
Study Arms  ICMJE
  • Experimental: Metastatic CRPC
    Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort A.
    Interventions:
    • Drug: Nivolumab
    • Drug: Ipilimumab
  • Experimental: Solid Tumors (non-prostate)
    Patients with all other metastatic subtypes will be enrolled in cohort B
    Interventions:
    • Drug: Nivolumab
    • Drug: Ipilimumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2018)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2021
Estimated Primary Completion Date September 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ajjai Alva, MD (734) 936-0091 ajjai@umich.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03570619
Other Study ID Numbers  ICMJE UMCC 2018.050
HUM00145104 ( Other Identifier: University of Michigan )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Michigan Rogel Cancer Center
Study Sponsor  ICMJE University of Michigan Rogel Cancer Center
Collaborators  ICMJE
  • Memorial Sloan Kettering Cancer Center
  • University of California, San Francisco
Investigators  ICMJE
Principal Investigator: Ajjai Alva, MD Rogel Cancer Center
PRS Account University of Michigan Rogel Cancer Center
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP