Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Prostatic Neoplasms, Castration-Resistant

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Docetaxel

Carboplatin

Taxane

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Twenty-five subjects with mismatch repair (MMR) intact

Twenty-five subjects with defective DNA repair

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

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.

Chemotherapy

Lawrence Fong, MD

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.

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).

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.

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

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

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 or death due to any cause, whichever occurs first. Radiographic tumor progression is defined according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines. The point estimate of 6-month rPFS rate and its 95% confidence interval will be obtained for each group, and will be compared by two-sample binomial test. The median rPFS and its 95% confidence interval will be obtained for each study group by Kaplan Meier method. Log rank test will be used to compare rPFS between the two study groups

Progression free survival is defined as the time from the first day of study treatment with pembrolizumab to the date of documented tumor progression or death due to any cause, whichever occurs first, as determined by immune-related response criteria (irRC) for immune-related progression free survival (irPFS) and RECIST v1.1 for PFS. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment. The point estimation and its 95% confidence interval of 20 weeks and 28 weeks irPFS rate and PFS rate will be obtained by study group and compared between the study groups by two-sample binomial test, separately. Kaplan-Meier method will be used to summarize PFS and irPFS; median irPFS and PFS will be estimated with 95% confidence interval in each study group. Log rank test will be used to compare the irPFS and PFS between the two groups, separately.

Compare the proportion of subjects achieving any PSA response from baseline in both study groups. The point estimate and its 95% confidence interval will be obtained for the proportion of PSA response separately for each study group. Two-sample binomial test will be used to compare the proportion of PSA response between the two study groups.

Proportion of subjects achieving any PSA decline ≥ 50% from baseline in both study groups. The point estimate and its 95% confidence interval will be obtained for the proportion of PSA decline \>= 50% separately for each study group. Two-sample binomial test will be used to compare the proportion of PSA response between the two study groups.

All subjects will be evaluated for toxicity from the time of the first treatment with pembrolizumab. Adverse events occurring from the start of treatment until 30 days after the end of treatment will be summarized by maximum toxicity grade for each study group and by strata. All treatment related adverse events will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0

For subjects 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. Log rank test will be used to compare the time to progression between the two study groups

Spots Global Cancer Trial Database for Pembrolizumab in Metastatic Castration Resistant Prostate Cancer (mCRPC) With or Without DNA Damage Repair Defects

Trial Identification

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Study Description

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