CASCARA: Castration Sensitive Carboplatin, Cabazitaxel and Abiraterone

NCT03934840 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018LS158c17-191
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 8

Brief Summary

This is a phase II clinical trial in patients with metastatic castration sensitive prostate cancer. The objective of the study is to determine the efficacy and further define the safety of the treatment combination. This study will evaluate dose levels of carboplatin AUC 4 with cabazitaxel 20 mg/m2. Patients will be treated with the combination of ADT and carboplatin and cabazitaxel for 6 cycles. After 6 cycles of chemotherapy, they will start abiraterone with ADT. The primary objective is to determine the percent of subjects that have no PSA or radiographic progression at 1 year. Secondary objectives will include determining the progression-free survival, time to PSA nadir and time to PSA progression of carboplatin and cabazitaxel in combination with ADT.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Prostate-Specific Antigen (PSA) or Radiographic Progression

  Proportion of patients who have no PSA or radiographic progression as determined by RECIST 1.1 or PCWG3 criteria

  1 Year

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  1 Year

• PSA Nadir

  1 Year

• Incidence of adverse events

  1 Year

• Incidence of Homologous Recombination Deficiency (HRD)

  1 Year

• PSA Complete Response Rate

  1 Year

Study Arms (1)

Carboplatin, Cabazitaxel and Abiraterone

EXPERIMENTAL

Drug: Cabazitaxel; Drug: Carboplatin; Drug: Abiraterone; Drug: Prednisone

Interventions

Cabazitaxel DRUG

20 mg/m2 Q 21 days

Carboplatin, Cabazitaxel and Abiraterone

Carboplatin DRUG

AUC 4 Q21 Days x 6 cycles with ADT

Carboplatin, Cabazitaxel and Abiraterone

Abiraterone DRUG

1000 mg PO daily

Carboplatin, Cabazitaxel and Abiraterone

Prednisone DRUG

5 mg PO daily on chemotherapy completion

Carboplatin, Cabazitaxel and Abiraterone

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide, or have a legally authorized representative provide, written informed consent and HIPAA authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
• Histologically confirmed prostate cancer.
• High volume metastatic disease (defined as the presence of visceral metastases or ≥3 bone lesions).
• ADT for ≤3 months by day 1 of study chemotherapy; Prior episodes of ADT are allowed (i.e. ADT used previously in courses of radiation).
• Testosterone \<50 ng/dL. Patients must continue primary ADT with an LHRH analogue if they have not undergone orchiectomy.
• ECOG Performance Status 0 or 1 (see Appendix A)
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count ≥ 1.5 × 10\^9/L
• Platelets ≥ 100 × 10\^9/L
• Hemoglobin ≥ 9 g/dl
• Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min
• In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 x ULN. If the patient has liver metastases, ALT and AST \<5 x ULN
• Total bilirubin \< ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome.
• Sexually active males must use a condom during intercourse while taking study drugs and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Fertile males must use a condom with spermicide (double barrier method).
• Age ≥ 18 years

You may not qualify if:

• Prior exposure to any chemotherapy, PARPi, or immunotherapy for prostate cancer.
• Prior abiraterone or enzalutamide, unless therapy was for \< 2 weeks
• Radiation therapy (including palliative radiotherapy to a metastatic lesion) within 14 days or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days of the date of the first dose.
• Other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is shorter, prior to day 1 of chemotherapy (with the exception of anti-androgens like bicalutamide).
• PSA \<2.0 ng/mL at diagnosis.
• If present, peripheral neuropathy must be ≤ Grade 1
• Patients with an active second malignancy that could, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) prior to starting the study treatment
• Clinically stable CNS tumor at the time of screening.
• Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement
• Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of treating investigator.
• Patient has a history of non-compliance to medical regimen or inability to grant consent.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (8)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Thomas Jeferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; Carboplatin; abiraterone; Prednisone

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; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Emmanuel Antonarakis, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: May 2, 2019
• Study Start: October 10, 2019
• Primary Completion: June 19, 2023
• Study Completion: May 1, 2025
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

US (8)