Docetaxel and Carboplatin for Patients With mCRPC and DNA-Repair Deficiencies

• Sponsor: Seattle Institute for Biomedical and Clinical Research (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02985021
• Collaborator: Prostate Cancer Foundation (Other), VA Puget Sound Health Care System (U.S. Fed)
• Enrollment: 2
• Locations: 3
• Arm: 1
• Duration (Months): 53
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

In this study, patients who have metastatic prostate cancer that does not respond to hormone treatment and who have mutations in certain cancer-related genes will be treated with docetaxel and carboplatin chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer	Drug: Carboplatin; Drug: Docetaxel	Phase 2

Detailed Description

This is a phase 2 study of the combination of docetaxel and carboplatin in patients with germline inactivation of genes in the homologous recombination pathway, including BRCA1, BRCA2, and Ataxia Telangiectasia Mutated (ATM).

PRIMARY OBJECTIVE To assess rate of 50% Prostate Specific Androgen (PSA) decline to docetaxel and carboplatin

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Docetaxel and Carboplatin for Treatment of Patients With Metastatic, Castration Resistant Prostate Cancer and Germline or Somatic DNA Repair Deficiency
• Study Start Date: Nov 1, 2016
• Actual Primary Completion Date: Apr 1, 2021
• Actual Study Completion Date: Apr 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (docetaxel, carboplatin) Docetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle. Docetaxel and carboplatin should be administered per institutional guidelines. Treatment will be repeated until disease progression or unacceptable toxicity.	Drug: Carboplatin; Chemotherapy; Other Names: Paraplatin ; Drug: Docetaxel; Chemotherapy; Other Names: Taxotere

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria [From Day 1 of treatment and up to 30 days after completion of treatment (typically up to 10 cycles of chemotherapy)]

   Achievement of a PSA50 decline is whether the treatment results in a 50% or greater decline in PSA from baseline PSA prior to therapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria

Patients meeting the following inclusion criteria will be eligible to participate in this study:

1. 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.

2. Age > 18 years

3. Known prostate cancer

4. 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.

5. Castration resistant prostate cancer as defined by serum testosterone < 50ng/ml and 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 (Response Evaluation Criteria in Solid Tumors).

• Progression of metastatic bone disease on bone scan with > 2 new lesions.

1. Prior therapy with abiraterone acetate, enzalutamide, or docetaxel. There is no limit to the number of prior treatment regimens.

2. Presence of metastatic disease on scans.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

4. Life expectancy >12 weeks.

5. No prior malignancy is allowed except:

• Adequately treated basal cell or squamous cell skin cancer or

• In situ carcinoma of any site or

• Other adequately treated malignancy for which the patient has been disease-free for at least one year (any prior chemotherapy is allowed).

1. Patients must have adequate organ and marrow function as defined below obtained within 14 days prior to start of therapy:

2. Absolute neutrophil count >1.5 x 109 cells/L

3. Hgb > 9.0 g/dL

4. Platelets >100,000 x 109/L

5. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels < 1.5 x Upper Limit of Normal (ULN)

6. Presence of germline inactivation of BRCA1, BRCA2, ATM OR one of the following:

• Patients with clearly deleterious germline mutations of other genes involved in homologous DNA repair may be included at the investigator's discretion.

• Patients with homozygous inactivation of genes involved in homologous recombination from primary or metastatic tumor as assessed by a Clinical Laboratory Improvement Amendments (CLIA) level assay for DNA sequencing may be included.

• Patients with a signature of homologous recombination deficiency in primary or metastatic tissue may be included (VA Puget Sound only).

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from the study:

1. Currently receiving active therapy for other neoplastic disorders.

2. Histologic evidence of small cell carcinoma (morphology alone - immunohistochemical evidence of neuroendocrine differentiation without morphologic evidence is not exclusionary).

3. Prior treatment with platinum-based chemotherapy for prostate cancer.

4. Known parenchymal brain metastasis.

5. Active or symptomatic viral hepatitis or chronic liver disease.

6. 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 or cardiac ejection fraction measurement of < 35 % at baseline, if done.

7. Treatment with an investigational therapeutic within 30 days of Cycle 1.

8. Patients with dementia/psychiatric illness/social situations limiting compliance with study requirements or understanding and/or giving of informed consent are not eligible

9. Any medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained are not eligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Greater Los Angeles - West LA	Los Angeles	California	United States	90073
2	VA Ann Arbor Health Care System	Ann Arbor	Michigan	United States	48105
3	VA Puget Sound Health Care System	Seattle	Washington	United States	98108

Sponsors and Collaborators

• Seattle Institute for Biomedical and Clinical Research
• Prostate Cancer Foundation
• VA Puget Sound Health Care System

Investigators

• Principal Investigator: Robert B Montgomery, MD, VA Puget Sound HCS
• Principal Investigator: Matthew Rettig, MD, VA Greater Los Angeles HCS

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 1, 2019
• Informed Consent Form - Feb 27, 2019

More Information

Publications

None provided.

• Responsible Party: Seattle Institute for Biomedical and Clinical Research
• ClinicalTrials.gov Identifier: NCT02985021
• Other Study ID Numbers: PugetSoundVA
• First Posted: Dec 7, 2016
• Last Update Posted: Aug 5, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Carcinoma; Prostatic Neoplasms; DNA Repair-Deficiency Disorders; Carboplatin; Docetaxel

Study Results

Participant Flow

Arm/Group Title	Treatment (Docetaxel, Carboplatin)
Arm/Group Description	Docetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle. Docetaxel and carboplatin should be administered per institutional guidelines. Treatment will be repeated until disease progression or unacceptable toxicity. Carboplatin: Chemotherapy Docetaxel: Chemotherapy
Period Title: Overall Study
STARTED	2
COMPLETED	1
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Docetaxel, Carboplatin)
Arm/Group Description	Docetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle. Docetaxel and carboplatin should be administered per institutional guidelines. Treatment will be repeated until disease progression or unacceptable toxicity. Carboplatin: Chemotherapy Docetaxel: Chemotherapy
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%
Patients with metastatic resistant prostate cancer (Count of Participants)
Count of Participants [Participants]	2 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria
Description	Achievement of a PSA50 decline is whether the treatment results in a 50% or greater decline in PSA from baseline PSA prior to therapy
Time Frame	From Day 1 of treatment and up to 30 days after completion of treatment (typically up to 10 cycles of chemotherapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Docetaxel, Carboplatin)
Arm/Group Description	Docetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle. Docetaxel and carboplatin should be administered per institutional guidelines. Treatment will be repeated until disease progression or unacceptable toxicity. Carboplatin: Chemotherapy Docetaxel: Chemotherapy
Measure Participants	2
Count of Participants [Participants]	2 100%

Adverse Events

Time Frame	From Day 1 of treatment and up to 30 days after completion of treatment (typically up to 10 cycles of chemotherapy (30 weeks))
Arm/Group Title	Treatment (Docetaxel, Carboplatin)
Arm/Group Description	Docetaxel 60 mg/m2 will be administered on Day 1 of each 21-day cycle. Carboplatin Area Under the Curve (AUC) 5 will be administered on Day 1 of each 21-day cycle. Docetaxel and carboplatin should be administered per institutional guidelines. Treatment will be repeated until disease progression or unacceptable toxicity. Carboplatin: Chemotherapy Docetaxel: Chemotherapy
All Cause Mortality
	Treatment (Docetaxel, Carboplatin)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Treatment (Docetaxel, Carboplatin)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Treatment (Docetaxel, Carboplatin)
	Affected / at Risk (%)	# Events
Total	0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.