Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

NCT02565901 | Terminated Phase 1 Results FDA Drug

• 5 other identifiers: 9388NCI-2015-01478P30CA015704P50CA097186RG1715104
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This partially randomized phase I/II trial studies the side effects and how well sirolimus works when given together with docetaxel and carboplatin in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). Biological therapies, such as sirolimus, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as docetaxel and carboplatin, 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 sirolimus together with docetaxel and carboplatin may kill more tumor cells.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Stage IV Prostate Cancer AJCC v7; Metastatic Malignant Neoplasm in the Bone

Outcome Measures

Primary Outcomes (2)

• Percentage Change in Deoxyribonucleic Acid (DNA) Damage Secretory Program Induction (DDSP) (Phase II)

  Will be determined by the level of genetic expression of WNT16, IL6, or SFRP2 in tissue after chemotherapy (carboplatin/docetaxel) compared to background/baseline measurement. The primary metric of DDSP induction will be quantitative reverse transcription-polymerase chain reaction, which is quantitative, but in the event of ribonucleic acid degradation in sample processing, the alternative measure will be immunohistochemistry (0-2 scale of expression).

  Baseline up to day 21 after starting treatment

• Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phases I and II)

  Safety will be assessed through summaries of adverse events, vital signs, physical examinations, and clinical laboratory test data. Adverse events will then be quantified via CTCAE 4.0.

  Up to 3 years

Secondary Outcomes (1)

• Percentage of Patients With Reduction in Prostate Specific Antigen According to the Prostate Cancer Working Group 2 (PCWG2) Criteria (Phases I and II)

  Baseline to up to 3 years

Study Arms (2)

Arm I (sirolimus, docetaxel, carboplatin)

EXPERIMENTAL

Patients receive docetaxel IV over 30-60 minutes and carboplatin IV over 30 minutes on day 1. Beginning in cycle 2 and continuing in subsequent cycles, patients also receive sirolimus PO on day -2. Treatment repeats every 21 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

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

Arm II (sirolimus, docetaxel, carboplatin)

EXPERIMENTAL

Patients receive sirolimus PO on day -2. Patients also receive docetaxel IV over 30-60 minutes and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 10 cycles in the absence of disease progression or unacceptable toxicity.

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

Interventions

Carboplatin DRUG

Given IV

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

Arm I (sirolimus, docetaxel, carboplatin); Arm II (sirolimus, docetaxel, carboplatin)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Arm I (sirolimus, docetaxel, carboplatin); Arm II (sirolimus, docetaxel, carboplatin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (sirolimus, docetaxel, carboplatin); Arm II (sirolimus, docetaxel, carboplatin)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, Rapamycin, SILA 9268A, WY-090217

Arm I (sirolimus, docetaxel, carboplatin); Arm II (sirolimus, docetaxel, carboplatin)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
• Histologically or cytologically confirmed carcinoma of the prostate (excluding neuroendocrine differentiation or squamous cell histology)
• Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
• Castration resistant prostate cancer as defined by serum testosterone \< 50 ng/ml and at least one of the following:
• PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
• Evaluable disease progression by modified RECIST 1.1
• Progression of metastatic bone disease on bone scan with \> 2 new lesions
• Prior therapy with abiraterone, enzalutamide and/or docetaxel; if a patient has not received docetaxel or cabazitaxel chemotherapy, the patient must be informed of this treatment choice as an alternative; if the patient has received docetaxel or cabazitaxel chemotherapy or refuses one of both of these therapies, this rationale must be documented and the patient is then eligible; patient must be offered and made aware of all Food and Drug Administration (FDA)-approved treatment options; patients with bone only disease may not have received radium-223
• The presence of metastatic disease amenable to computed tomography (CT) or ultrasound guided biopsy; this may include thoracolumbar vertebral bodies, pelvis, femur or humerus or soft tissue or nodal metastasis amenable to biopsy (excluding lung or pleural lesions)
• Agree to participate in biopsy of metastatic lesion during the study at day 21
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Life expectancy \>= 12 weeks
• No prior malignancy is allowed except:
• Adequately treated basal cell or squamous cell skin cancer or
• In situ carcinoma of any site or

You may not qualify if:

• Patients currently receiving active therapy for other neoplastic disorders
• Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible
• Patients with disease only in the bone previously treated with radium-223 will not be eligible
• Known parenchymal brain metastasis
• Active or symptomatic viral hepatitis or chronic liver disease
• Estimated creatinine clearance less than 50 ml/minute
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease
• Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
• Administration of an investigational therapeutic within 30 days of cycle 1, day -2
• Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent
• Patients with medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible
• Any condition which, in the opinion of the investigator, would preclude participation in this trial
• Patients on anticoagulation therapy which cannot be held for metastatic biopsies

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Carboplatin; Docetaxel; Sirolimus

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; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Bruce Montgomery
• Organization: University of Washington

rbmontgo@uw.edu

206-598-0860

Study Officials

• Robert Montgomery

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medical Oncology Division University of Washington School of Medicine

Study Record Dates

• First Submitted: September 25, 2015
• First Posted: October 1, 2015
• Study Start: February 29, 2016
• Primary Completion: June 16, 2020
• Study Completion: June 16, 2020
• Last Updated: October 1, 2021
• Results First Posted: October 1, 2021

Record last verified: 2021-09

Locations

US (1)