Experimental M6620 & Carboplatin, With or Without Docetaxel For Metastatic Castration-Resistant Prostate Cancer

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Age: 18 years or older
Gender:
Male
Healthy Volunteers: No
Keywords: Prostate Cancer
Type: Drug study, Phase 2
Target:
136 Participants
Investigator:
Description
This study is being done to answer the following question:

Will your prostate cancer shrink if we add the experimental drug M6620 to standard treatment? Standard treatment for prostate cancer uses a chemotherapy drug called carboplatin.

We are doing this study to find out if this approach is better or worse than standard treatment for your cancer.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  • Participants must have histologically or cytologically confirmed prostate cancer
  • 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 =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • 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 or ECOG performance status (PS) = 2 are allowed on study, but if randomized to Arm A will receive carboplatin as a single agent (AUC 5) rather than docetaxel+carboplatin; they must be fit for carboplatin chemotherapy as determined by the treating investigator
  • Willing to undergo core biopsy of a recurrent/metastatic lesion adequate for next generation sequencing (NGS) 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
  • The effects of M6620, 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 administration
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria:

  • 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 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
  • M6620 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) should be avoided; 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
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
You will not be paid to take part in this research study.
Resources
Schedule
Study duration and period
You will receive study treatment as long as your cancer is not getting worse and you are not having difficult side effects. After you finish your study drug dosing, your doctor will continue to follow your condition for up to 42 days to watch you for side effects. After that the study team will continue to follow-up with your health status.
Recruitment period
From Jan. 3, 2019
Location
UC Davis Comprehensive Cancer Center
4501 X Street
Sacramento, CA 95817
Research Topic
Conditions:
  • Castration-Resistant Prostate Carcinoma
  • Metastatic Prostate Carcinoma
  • Stage IV Prostate Cancer AJCC v8

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