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Castration-Resistant Prostate CarcinomaPhase 2NCT03517969

M6620 and Carboplatin With or Without Docetaxel in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

A Phase 2 study testing Berzosertib, Carboplatin and Docetaxel in people with Castration-Resistant Prostate Carcinoma and Metastatic Prostate Carcinoma, run by National Cancer Institute (NCI) at 23 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well berzosertib (M6620) and carboplatin with or without docetaxel works in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Berzosertib, Carboplatin and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
73 participants
Where
23 sitesUnited States
Study dates
29 May 2019to 3 Apr 2027
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

  • Participants must have histologically or cytologically confirmed prostate cancer (code 10036910) with progressive disease at the time of study entry by either
  • Sequence of at least 2 rising PSA values at a minimum of 1-week intervals
  • Radiographic progression per RECIST1.1 for soft tissue and/or per PCWG3^2 for bone, with or without PSA progression
  • Patients must have metastatic disease by bone scan or other nodal or visceral lesions on computed tomography (CT) or magnetic resonance imaging (MRI) and a castrate level of testosterone (< 50 ng/dL) and evaluable for disease response by either
  • Baseline PSA >= 2.0 ng/mL OR
  • Measurable disease per RECIST 1.1
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  • NOTE: Subjects must maintain a castrate state; if they have not had an orchiectomy, they must continue to receive luteinizing hormone-releasing hormone (LHRH) or gonadotropin-releasing hormone (GnRH) agonists or antagonists unless intolerant
  • At least 2 prior treatments for castration resistant prostate cancer as follows:
  • Past progression or intolerance to at least one secondary hormonal therapy (abiraterone, enzalutamide, galeterone, apalutamide, darolutamide, orteronel, seviteronel or equivalent)
  • Past progression or intolerance to taxane-based chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9 g/dL (transfusion permitted)
  • Platelets >= 150,000/mcL (without transfusion or growth factor in prior 28 days)
  • Total bilirubin =< 1.5 x institutional upper limit of normal, unless the subject has known or suspected Gilbert's syndrome
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal or =< 5 x if presence of liver metastases
  • Creatinine clearance >= 40 mL/min/1.73 m^2
  • Prior treatment with mTOR inhibitors, cytostatic tyrosine kinase inhibitor (TKI), or biologic therapies allowed
  • Prior treatment with PARP inhibitors permitted
  • Patients with allergy or intolerance to docetaxel, grade 2 neuropathy are allowed on study, but if randomized to Arm A will receive carboplatin as a single agent (area under curve [AUC] 5) rather than docetaxel+carboplatin; they must be fit for carboplatin chemotherapy as determined by the treating investigator
  • Presence of a lesion (bone or soft tissue) amenable to image-guided percutaneous biopsy adequate for next generation sequencing (NGS), and planned to undergo core biopsy after trial registration but prior to cycle 1 day 1 of therapy; confirmation of adequacy of this biopsy material for NGS is NOT required for initiation of therapy; if elective biopsies are not being performed at the treating institution due to preparations or precautions related to coronavirus disease 2019 (COVID-19), this requirement can be waived on discussion with the trial principal investigator (PI)
  • The effects of M6620 (VX-970, berzosertib), carboplatin and docetaxel on the developing human fetus are unknown. For this reason and because DNA-damage response inhibitors and chemotherapeutic agents are known to be teratogenic, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of carboplatin and M6620 (VX-970, berzosertib) administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to planned cycle 1 day 1 of study treatment; patients on an oral anti-neoplastic such as an oral hormonal agent, PARP inhibitor or oral experimental agent should discontinue >= 14 days prior to planned cycle 1 day 1 of study treatment
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), except for grade 2 anorexia, alopecia, neuropathy, and fatigue, for which resolution is not required
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases or leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to M6620 (VX-970, berzosertib) or carboplatin; (patients with allergy to docetaxel will be allowed on study, but docetaxel will be excluded from their treatment regimen)
  • Subjects receiving treatment with ototoxic or nephrotoxic medications that cannot be discontinued at least 7 days before first dose of carboplatin and for the duration of the study; inadvertent or short-term use on study will not cause a subject to be ineligible; if a short course of therapy with nephrotoxic or ototoxic medication is anticipated and required, carboplatin should be discontinued until 7 days after this course is completed; patients on continuous medications that are potentially nephrotoxic who have had no evidence of nephrotoxicity from these medications at study entry are allowed to continue those medicines on trial
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  • M6620 (VX-970, berzosertib) is primarily metabolized by CYP3A4; therefore, concomitant administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir) or inducers of CYP3A4 (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) is prohibited; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; Patient Drug Information Handout and Wallet Card should be provided to patients; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant and nursing women are excluded from this study because they do not develop prostate cancer
  • Human immunodeficiency (HIV)-positive participants with detectable viral load and/or CD4 count =< 300 are ineligible due to increased risk of lethal infections when treated with marrow-suppressive therapy; HIV-positive patients with undetectable viral loads and CD4 counts > 300, and not on interacting antiretroviral therapy may be eligible after discussing with the principal investigator
  • Prior treatment with platinum-containing regimen or ATR inhibitor for prostate cancer

Trial locations and contacts

23 sites in 1 country.

23 sites in 1 country

United States23 sites

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Smilow Cancer Center/Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Yale University

    New Haven, Connecticut, 06520

  • Yale-New Haven Hospital North Haven Medical Center

    North Haven, Connecticut, 06473

  • Smilow Cancer Hospital-Orange Care Center

    Orange, Connecticut, 06477

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • Smilow Cancer Hospital-Torrington Care Center

    Torrington, Connecticut, 06790

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

Other trials in United States

About this study

Official title: A Phase 2 Study of M6620 (VX-970, Berzosertib) in Combination With Carboplatin Compared With Docetaxel in Combination With Carboplatin in Metastatic Castration-Resistant Prostate Cancer

This phase II trial studies how well berzosertib (M6620) and carboplatin with or without docetaxel works in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). M6620 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving M6620, carboplatin and docetaxel may work better in treating patients with metastatic castration-resistant prostate cancer compared to carboplatin and docetaxel alone.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the difference in response rate (either achievement of prostate specific antigen [PSA] reduction of greater than 50% or radiographic response by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) of the combination of berzosertib (M6620) (VX-970, berzosertib) and carboplatin as compared to the combination of docetaxel and carboplatin.

SECONDARY OBJECTIVES:

  1. To assess the difference in time to PSA progression by Prostate Cancer Working Group (PCWG)2 criteria of the combination of M6620 (VX-970, berzosertib) and carboplatin as compared to the combination of docetaxel and carboplatin.

II. To describe radiographic progression-free survival and progression-free survival by PCWG3 criteria in both arms of the study.

III. Assess the relationship with homologous recombination deficiency (HRD) detected from baseline tumor biopsy with response to the combination of M6620 (VX-970, berzosertib) and carboplatin and the combination of docetaxel and carboplatin.

IV. To describe the safety and adverse events from the combination of M6620 (VX-970, berzosertib) + carboplatin as well the combination of docetaxel + carboplatin.

EXPLORATORY OBJECTIVES:

  1. Comparison of overall survival in the two arms of the study. II. Explore response rate, time to PSA progression, radiographic progression-free survival, and progression-free survival by PCWG3 criteria in patients who initially receive docetaxel + carboplatin after crossover to M6620 + carboplatin.

III. To assess the relationship with homologous recombination deficiency (HRD) detected from baseline circulating free deoxyribonucleic acid (DNA) (cfDNA) with response to the combination of M6620 and carboplatin and the combination of docetaxel and carboplatin, and describe alterations seen in cfDNA (and optional tumor biopsy) at end of study.

OUTLINE: Patients are randomized to 1 of 2 groups.

ARM A (docetaxel, carboplatin): Patients receive docetaxel intravenously (IV) over 60 minutes and carboplatin IV over 30 minutes on day 1 or carboplatin alone on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients have PSA progression or radiographic progression may crossover to Arm B.

ARM B (carboplatin, berzosertib): Patients receive carboplatin IV over 30 minutes on day 1 and berzosertib IV over 60-90 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up between 30-42 days.

Being tested
Berzosertib, Carboplatin, Docetaxel, Laboratory Biomarker Analysis
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • BerzosertibDrug

    Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • DocetaxelDrug

    Also called Docecad, RP 56976, RP-56976, RP56976

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT03517969
Study groupRoleWhat they receive
Arm A (docetaxel, carboplatin)Active comparatorPatients receive docetaxel IV over 60 minutes and carboplatin IV over 30 minutes, or carboplatin alone on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who have PSA progression or radiographic progression may crossover to Arm B.
Receives: Drug: Carboplatin; Drug: Docetaxel; Other: Laboratory Biomarker Analysis
Arm B (carboplatin, berzosertib)ExperimentalPatients receive carboplatin IV over 30 minutes on day 1 and berzosertib IV over 60-90 minutes on days 2 and 9. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Berzosertib; Drug: Carboplatin; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Overall Response Rate

    Defined by radiographic response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or prostate specific antigen [PSA] response (> 50% decline from baseline).

    Measured: Radiologic measurements are performed every 3 cycles Up to 2 years. PSA measurements are performed every cycle up to 2 years

Secondary outcomes (4)

  1. Progression-free Survival (PFS)

    Assessed by Prostate Cancer Working Group (PCWG) 3 criteria. PFS to be estimated with the Kaplan Meier methodology. Median will be provided with 95% confidence interval.

    Measured: From the time of randomization up to 2 years

  2. Time to PSA Progression

    Assessed by PCWG2. PSA progression will be estimated with the Kaplan Meier methodology. Median will be provided with 95% confidence interval.

    Measured: From the time of randomization up to 2 years

  3. Radiographic Progression-free Survival (rPFS)

    Assessed by RECIST 1.1 for non-osseous disease and by PCWG3 for osseous disease. rPFS will be estimated with the Kaplan Meier methodology. Median will be provided with 95% confidence interval.

    Measured: From the time of randomization up to 2 years

  4. Incidence of Adverse Events

    Adverse events will be graded and analyzed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Up to 2 years (from treatment initiation to 30 days after the last dose of study treatment)

Timeline

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

  1. First posted8 May 2018
  2. Study start29 May 2019
  3. Primary completion10 Aug 2021
  4. Study completion3 Apr 2027 (estimated)

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03517969
Sponsor's protocol ID
NCI-2018-00790
Other IDs
NCI-2018-00790, 10191, 10191, UM1CA186709
Status last verified
Oct 2026
First submitted
7 May 2018
Last updated
9 Oct 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Berzosertib, Carboplatin and Docetaxel in people with Castration-Resistant Prostate Carcinoma and Metastatic Prostate Carcinoma, run by National Cancer Institute (NCI) at 23 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 24 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 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 8 May 2025). 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?

Overall Response Rate (time frame: Radiologic measurements are performed every 3 cycles Up to 2 years. PSA measurements are performed every cycle up to 2 years). 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 NCT03517969.

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 9 Oct 2026.

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