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Castration Resistant Prostatic CancerPhase 2NCT03248570

Pembrolizumab in Metastatic Castration Resistant Prostate Cancer (mCRPC) With or Without DNA Damage Repair Defects

A Phase 2 study testing Pembrolizumab and Chemotherapy in people with Castration Resistant Prostatic Cancer and Metastatic Prostate Cancer, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a multicenter phase 2 open label study of pembrolizumab in patients with metastatic castrate resistant prostate cancer (mCRPC) with or without DNA damage repair defects. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Pembrolizumab and Chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
20 Feb 2018to 28 Sep 2023
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
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented histology of adenocarcinoma of the prostate.
  • Metastatic castration resistant prostate cancer with castrate-level testosterone (<50 ng/dL).
  • Subjects must maintain a castrate-level testosterone during the study.
  • Disease progression defined by one or more of the following three criteria:
  • Prostate-specific antigen (PSA) > 2.0 ng/mL and rising PSA by at least 2 consecutive measurements a minimum of 1-week apart.
  • Soft tissue progression as defined by RECIST v1.1 criteria.
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  • Bone disease progression as defined by Prostate Cancer Clinical Trials Working Group 3 (PCWG3).
  • Have received prior secondary hormonal therapy including abiraterone, enzalutamide and/or apalutamide.
  • Be taking prednisone at a dose of ≤ 10mg/day, 7 days prior to starting treatment (Cycle 1, Day 1).
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be >= 18 years of age on day of signing informed consent.
  • Patients must agree to have a tumor tissue biopsy at baseline, and there must be a lesion that can be biopsied with acceptable clinical risk as judged by the investigator.
  • Patients with inconclusive DNA damage repair status testing on this baseline biopsy must have one of the following (per the investigator's discretion): (i) Sufficient archival tissue, or (ii) An additional biopsy attempt.
  • Patients with previously identified homozygous deletion or deleterious germline or somatic mutation(s) in DNA damage repair gene(s) (such as BReast CAncer gene 1 (BRCA1) , BReast CAncer gene 2 (BRCA2), and ATM) identified in a Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified laboratory are allowed in Group 2. (i) Somatic mutation(s) in DNA damage repair gene(s) needs to be identified on the biopsy of a castration-resistant tumor site (ii) Archival FFPE tissue will be requested for determination of MSI (if not already assessed by gene sequencing) signature status.(iia) A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report before study enrollment. (iii) If archival FFPE tissue is unable to be obtained or is insufficient, patients will be required to undergo tumor tissue biopsy if feasible for determination of MSI signature status.
  • Patients with germline mutation(s) in mismatch repair (MMR) gene(s) (i.e. Lynch syndrome),or have previously identified Microsatellite instability (MSI)-high tumor by Polymerase chain reaction (PCR) or MMR deficient tumor by Immunohistochemistry (IHC) are also allowed in Group 2. (i) Archival FFPE tissue will be requested for determination of Fanconi anaemia (FA)/BRCA signature status. (ia) A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report before study enrollment. (ii) If archival FFPE tissue is unable to be obtained or is insufficient, patients will be required to undergo tumor tissue biopsy if feasible for determination of FA/BRCA signature status.
  • If group 1 is not filled, patients may proceed onto treatment without the completion of tests for DNA repair status. Once group 1 is filled, patients cannot be enrolled onto the study or start treatment until DNA damage repair status is successfully determined for study group placement.
  • Patients will be replaced if they have tissues that are not evaluable for DNA repair mutations
  • Patients must be willing to provide archival tissue from prior biopsy or surgery for prostate cancer, if available.
  • A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or at least 10 slides containing unstained, freshly cut, serial sections must be available along with an associated pathology report before study enrollment.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Patients must discontinue antiandrogen therapy (i.e. bicalutamide, flutamide, nilutamide) at least 4-6 weeks prior to registration with no evidence of PSA decline after washout.
  • Bicalutamide: Washout period at least 6 weeks
  • Flutamide and nilutamide: Washout period at least 4 weeks
  • Patients must discontinue therapies for mCRPC, with the exception of Gonadotropin-releasing hormone (GnRH) agent, for 14 days, with the exception of anti-androgens with which there may be a withdrawal PSA response.
  • Prior chemotherapy is allowed if no progression of disease on chemotherapy.
  • Prior treatment with sipuleucel-T, radium-223, or poly ADP-ribose polymerase (PARP) inhibitor (e.g. olaparib) is allowed.
  • Tissue biopsy may be performed during washout period.
  • Demonstrate adequate organ function as defined as follows, all screening labs should be performed within 28 days of treatment initiation.
  • Hematological: (i) Absolute neutrophil count (ANC): >= 1,500 /microliters (mcL) (ii) Platelets: >= 100,000 / mcL (iii) Hemoglobin: >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Renal: (i) Serum creatinine OR Measured or calculated a creatinine clearance (GFR can also be used in place of creatinine or CrCl): <=1.5 X upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. Creatinine clearance should be calculated per institutional standard
  • Hepatic: (i) Serum total bilirubin: <= 1.5 X ULN (ii) Aspartate Aminotransferase (AST) (SGOT) and Alanine Aminotransferase (ALT) (SGPT): <= 2.5 X ULN OR <= 5 X ULN for subjects with liver metastases (iii) Albumin: >= 2.5 mg/dL
  • Coagulation: (i) International Normalized Ratio (INR) or Prothrombin Time (PT): <= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or Partial Thromboplastin Time (PTT) is within therapeutic range of intended use of anticoagulants (ii) Activated Partial Thromboplastin Time (aPTT): <= 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Who cannot join

  • Significant liver metastasis.
  • Prior taxane-based chemotherapy with progressive disease on chemotherapy.
  • Prior docetaxel for metastatic hormone sensitive prostate cancer is allowed, if no progression of disease on docetaxel as defined by RECIST v1.1 and PCWG3.
  • Prior taxane-based chemotherapy (i.e. docetaxel or cabazitaxel with or without platinum agent) for mCRPC is allowed if no progression of disease on chemotherapy as defined by RECIST v1.1 and PCWG3.
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy >10mg/day or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
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  • Has a known history of active Bacillus Tuberculosis (TB).
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., <= Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with <= Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy <= 10 mg of prednisone/day for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is expecting to father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (HBV) (i.e Hepatitis B surface antigen (HBsAg) reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) RNA [qualitative] is detected).
  • Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase 2 Open Label Study of Pembrolizumab in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) With or Without DNA Damage Repair Defects

This is a multicenter phase 2 open label study of pembrolizumab in patients with metastatic castrate resistant prostate cancer (mCRPC) with or without DNA damage repair defects.

Read the detailed description

This is a multicenter phase 2 open label study of pembrolizumab in patients with metastatic castrate resistant prostate cancer (mCRPC) with or without DNA damage repair defects.

All subjects will receive pembrolizumab 200mg intravenously (IV) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint of the study is objective response rate (ORR) according to immune-mediated response criteria (irRC).

Being tested
Pembrolizumab, Chemotherapy
Medical subject headings
Prostatic Neoplasms, Castration-Resistant, Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called KEYTRUDA, MK-3475

    All subjects will receive pembrolizumab 200mg IV every 3 weeks until disease progression or unacceptable toxicity.

  • ChemotherapyDrug

    At time of progression, all subjects will also have the option of receiving taxane-based chemotherapy followed by repeat pembrolizumab for those who have a clinical response to chemotherapy. Chemotherapy regimen will be at the discretion of the treating physician, and may consist of docetaxel or cabazitaxel with or without a platinum agent (e.g. carboplatin). A minimum of 4 cycles and a maximum of 8 cycles of chemotherapy will be given.

Study groups in NCT03248570
Study groupRoleWhat they receive
DNA damage repair proficient groupExperimentalParticipants with mismatch repair (MMR) intact receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. If disease worsens while receiving pembrolizumab, participants may receive standard of care chemotherapy for 2-8 cycles
Receives: Drug: Pembrolizumab; Drug: Chemotherapy
DNA damage repair defective groupExperimentalParticipants with defective DNA repair receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. If disease worsens while receiving pembrolizumab, participants may receive standard of care chemotherapy for 2-8 cycles
Receives: Drug: Pembrolizumab; Drug: Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Radiographic Progression-Free Survival Rate (rPFS) at 6 Months

    The rPFS rate is defined as the proportion of participants still alive at 6 months starting from the first day of study treatment with pembrolizumab. Participants will be censored on the date of documented tumor progression according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines or death due to any cause at 6 months. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. The 6-month rPFS rate and the 95% confidence interval will be reported by study group.

    Measured: Up to 6 months

  2. Median Overall Radiographic Progression-free Survival (rPFS)

    The median overall radiographic progression free survival (rPFS) is defined as the time from the first day of study treatment with pembrolizumab to the date of documented radiographic tumor progression according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines or death due to any cause, whichever occurs first. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. The median time in months and the 95% confidence interval will be reported by study group.

    Measured: Up to 24 months

Secondary outcomes (8)

  1. Immune-related Progression-free Survival Rate (irPFS) at 20 Weeks

    The immune-related Progression Free Survival rate (irPFS) is defined as the proportion of participants still alive at 20 weeks from the first day of study treatment with pembrolizumab. Participants will be censored on the date of documented tumor progression according to the immune-related response criteria (irRC) for immune-related progression or death due to any cause at 20 weeks. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. The 20-week irPFS rate and the 95% confidence interval will be reported by study group.

    Measured: Up to 20 weeks

  2. Immune-related Progression-free Survival Rate (irPFS) at 28 Weeks

    The immune-related Progression Free Survival rate (irPFS) is defined as the proportion of participants still alive at 28 weeks from the first day of study treatment with pembrolizumab. Participants will be censored on the date of documented tumor progression according to the immune-related response criteria (irRC) for immune-related progression or death due to any cause at 28 weeks. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. The 28-week irPFS rate and the 95% confidence interval will be reported by study group.

    Measured: Up to 28 weeks

  3. Overall Progression-Free Survival Rate (PFS) at 20 Weeks

    The overall progression free survival rate (PFS) is defined as the proportion of participants still alive from the first day of study treatment with pembrolizumab at 20 weeks. Participants will be censored on the date of documented tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines or death due to any cause at 20 weeks. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. The 20-week overall PFS rate and the 95% confidence interval will be reported by study group.

    Measured: Up to 20 weeks

  4. Overall Progression-Free Survival Rate (PFS) at 28 Weeks

    The overall progression free survival rate (PFS) is defined as the proportion of participants still alive from the first day of study treatment with pembrolizumab at 28 weeks. Participants will be censored on the date of documented tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines or death due to any cause at 28 weeks. Participants who did not progress or die will be censored on the date of their last evaluable tumor assessment. The 28-week overall PFS rate and the 95% confidence interval will be reported by study group.

    Measured: Up to 28 weeks

  5. Percentage of Participants Achieving Any Prostate Specific Antigen (PSA) Response

    The percentage of participants with a demonstrated PSA response will be reported for each group along with the 95% confidence interval.

    Measured: Up to 24 months

  6. Percentage of Participants Achieving Any PSA Decline ≥ 50%

    The percentage of participants with a demonstrated PSA decline >= 50% will be reported for each group along with the 95% confidence interval.

    Measured: Up to 24 months

  7. Number of Participants Reporting Any Pembrolizumab Treatment-related Adverse Events

    All participants will be evaluated for toxicity from the time of the first treatment with pembrolizumab. The number of participants with adverse events defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and categorized as having a possible, probable, or definite attribution to the administration of pembrolizumab from the start of treatment until 30 days after the end of treatment will be reported for each group.

    Measured: Up to 24 months

  8. Median Time to Progression After Taxane-based Chemotherapy

    For participants who undergo taxane-based chemotherapy after progression on pembrolizumab followed by repeat pembrolizumab after chemotherapy, time from the first chemotherapy treatment to disease progression will be estimated in both study groups. Disease progression will be defined by confirmed PSA progression on two consecutive measurements at least 2 weeks apart, or radiographic progression by irRC. The Kaplan-Meier method will be used to estimate the median time to progression with 95% confidence interval by study group.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2017
  2. Study start20 Feb 2018
  3. Primary completion28 Sep 2023
  4. Study completion28 Sep 2023

Resources

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
Model description
After determination of DNA damage repair status, subjects will be assigned to one of two treatment groups: * Group 1 (DNA damage repair proficient group): Twenty-five subjects * Group 2 (DNA damage repair deficient group): Twenty-five subjects All subjects will receive pembrolizumab 200mg IV every 3 weeks until disease progression or unacceptable toxicity.
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03248570
Sponsor's protocol ID
16557
Other IDs
NCI-2017-02408, R01CA223484
Status last verified
Oct 2024
First submitted
9 Aug 2017
Last updated
20 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Chemotherapy in people with Castration Resistant Prostatic Cancer and Metastatic Prostate Cancer, run by University of California, San Francisco at 1 site 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 33 inclusion and 24 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 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 20 Nov 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?

Radiographic Progression-Free Survival Rate (rPFS) at 6 Months (time frame: Up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03248570.

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 20 Nov 2024.

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