Metastatic Castration Resistant Prostate CancerPhase 2IMPACTNCT03570619
Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Castration Resistant Prostate Cancer and Metastatic Cancer, run by University of Michigan Rogel Cancer Center at 8 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Castration Resistant Prostate Cancer, Metastatic Cancer, Solid Tumor
- What is being tested?
- Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 8 sitesUnited States
- Study dates
- 14 Dec 2018to 26 Mar 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Karmanos Cancer Institute
Detroit, Michigan, 48201
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California San Diego, Moores Cancer Center
San Diego, California, 92093
University of California San Francisco/Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110
H. Lee. Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, 33612
About this study
Official title: IMPACT: Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
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.
Read the 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.
- Being tested
- Nivolumab, Ipilimumab
- Keywords
- Metastatic Cancer, Metastatic Castration Resistant Prostate Cancer, mCRPC, Immunotherapy, CDK12, Solid Tumor
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
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.
IpilimumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Metastatic CRPC | Experimental | Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort A. Receives: Drug: Nivolumab; Drug: Ipilimumab |
| Solid Tumors (non-prostate) | Experimental | Patients with all other metastatic subtypes will be enrolled in cohort B Receives: Drug: Nivolumab; Drug: Ipilimumab |
| Metastatic CRPC with Monotherapy | Experimental | Patients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort C once enrollment to cohort A has been completed. Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Patients With CDK12 Loss of Function Metastatic CRPC That Respond to 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.
Measured: Up to 24 months post treatment
Secondary outcomes (8)
The Proportion of Patients That Respond to Treatment in Cohort B.
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.
Measured: Up to 104 weeks after start of therapy
Radiographic Progression Free Survival Time (rPFS)
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.
Measured: Up to 104 weeks after start of therapy
Progression Free Survival Time (PFS)
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.
Measured: Up to 24 months post treatment
Duration of Therapy (DOT)
Defined by the time interval from the start of treatment to the day of permanent discontinuation of treatment (including death).
Measured: Up to 104 weeks after start of therapy
Progression Rate at 6 Months
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.
Measured: 6 months
Overall Survival Time
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.
Measured: Up to 24 months post treatment
PSA Progression Free Survival Time
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.
Measured: Up to 24 months post treatment
Time to PSA Progression
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.
Measured: Up to 24 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2018
- Study start14 Dec 2018
- Primary completion22 Dec 2022
- Study completion26 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Castration Resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ajjai Alva, MD, Principal investigator, Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03570619
- Sponsor's protocol ID
- UMCC 2018.050
- Other IDs
- HUM00145104
- Acronym
- IMPACT
- Status last verified
- Apr 2025
- First submitted
- 15 Jun 2018
- Last updated
- 8 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPACT: Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
- ClinicalTrials.gov ID
- NCT03570619
- Acronym / sponsor ID
- IMPACT / UMCC 2018.050
- Keywords
- Metastatic Cancer, Metastatic Castration Resistant Prostate Cancer, mCRPC, Immunotherapy, CDK12, Solid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center, University of California, San Francisco
- Study start
- 14 Dec 2018 (actual)
- Primary completion
- 22 Dec 2022 (actual)
- Study completion
- 26 Mar 2024 (actual)
- First posted
- 27 Jun 2018 (actual)
- Results
- Posted 30 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Metastatic CRPC | Experimental | Drug: Nivolumab, Drug: IpilimumabPatients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort A. |
| Solid Tumors (non-prostate) | Experimental | Drug: Nivolumab, Drug: IpilimumabPatients with all other metastatic subtypes will be enrolled in cohort B |
| Metastatic CRPC with Monotherapy | Experimental | Drug: NivolumabPatients with metastatic castration resistant prostate cancer (mCRPC) will be enrolled in cohort C once enrollment to cohort A has been completed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabPatients 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. | Drug | Metastatic CRPC, Metastatic CRPC with Monotherapy, Solid Tumors (non-prostate) |
| IpilimumabPatients 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. | Drug | Metastatic CRPC, Solid Tumors (non-prostate) |
Primary outcome
The Proportion of Patients With CDK12 Loss of Function Metastatic CRPC 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.
8 secondary outcomes
The Proportion of Patients That Respond to Treatment in Cohort B.
Time frame: Up to 104 weeks after start of therapy
Radiographic Progression Free Survival Time (rPFS)
Time frame: Up to 104 weeks after start of therapy
Progression Free Survival Time (PFS)
Time frame: Up to 24 months post treatment
Duration of Therapy (DOT)
Time frame: Up to 104 weeks after start of therapy
Progression Rate at 6 Months
Time frame: 6 months
Overall Survival Time
Time frame: Up to 24 months post treatment
PSA Progression Free Survival Time
Time frame: Up to 24 months post treatment
Time to PSA Progression
Time frame: Up to 24 months post treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Metastatic Castration Resistant Prostate Cancer
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STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
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ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
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Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ajjai Alva, MD principal investigator
Rogel Cancer Center
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Castration Resistant Prostate Cancer and Metastatic Cancer, run by University of Michigan Rogel Cancer Center at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Patients With CDK12 Loss of Function Metastatic CRPC That Respond to Treatment. (time frame: Up to 24 months post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.