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

NCT03517969 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2018-0079010191UM1CA186709
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 23

Brief 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). 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.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  From the time of randomization up to 2 years

• Time to PSA Progression

  From the time of randomization up to 2 years

• Radiographic Progression-free Survival (rPFS)

  From the time of randomization up to 2 years

• Incidence of Adverse Events

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

Other Outcomes (2)

• Overall Survival (OS)

  From the time of randomization up to 2 years

• Gene Mutation Frequencies

  At baseline

Study Arms (2)

Arm A (docetaxel, carboplatin)

ACTIVE COMPARATOR

Patients 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.

Drug: Carboplatin; Drug: Docetaxel; Other: Laboratory Biomarker Analysis

Arm B (carboplatin, berzosertib)

EXPERIMENTAL

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.

Drug: Berzosertib; Drug: Carboplatin; Other: Laboratory Biomarker Analysis

Interventions

Berzosertib DRUG

Given IV

Also known as: 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970, VX-970, VX970

Arm B (carboplatin, berzosertib)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm A (docetaxel, carboplatin); Arm B (carboplatin, berzosertib)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP 56976, RP-56976, RP56976, Taxotere, Taxotere Injection Concentrate

Arm A (docetaxel, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (docetaxel, carboplatin); Arm B (carboplatin, berzosertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (23)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418, United States

Location

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, 06824, United States

Location

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

Location

Smilow Cancer Hospital-Orange Care Center

Orange, Connecticut, 06477, United States

Location

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790, United States

Location

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

Location

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, 06708, United States

Location

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, 06385, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

berzosertib; Carboplatin; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Atish D Choudhury
• Organization: Dana Farber Cancer Institute

atish_choudhury@dfci.harvard.edu

617-6326328

Study Officials

• Atish D Choudhury

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2018
• First Posted: May 8, 2018
• Study Start: May 29, 2019
• Primary Completion: August 10, 2021
• Study Completion (Estimated): April 3, 2027
• Last Updated: April 23, 2026
• Results First Posted: May 8, 2025

Record last verified: 2026-04

Locations

US (23)