CASCARA: Castration Sensitive Carboplatin, Cabazitaxel and Abiraterone

Prostate Cancer Clinical Trial

Official title:

A Phase II Study of Carboplatin, Cabazitaxel and Abiraterone in High Volume Metastatic Castration Sensitive Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03934840
• Other study ID #: 2018LS158
• Secondary ID: c17-191
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 10, 2019
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 22
• Est. completion date: May 2025
• Est. primary completion date: June 19, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Cabazitaxel
20 mg/m2 Q 21 days
• Carboplatin
AUC 4 Q21 Days x 6 cycles with ADT
• Abiraterone
1000 mg PO daily
• Prednisone
5 mg PO daily on chemotherapy completion

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Tulane University	New Orleans	Louisiana
United States	Thomas Jeferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Lifespan Cancer Institute	Providence	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression-Free Survival (PFS)	Incidence of PFS	1 Year
Secondary	PSA Nadir	Time to time to PSA nadir	1 Year
Secondary	Incidence of adverse events	Safety and Tolerability	1 Year
Secondary	Incidence of Homologous Recombination Deficiency (HRD)	Incidence of HRD	1 Year
Secondary	PSA Complete Response Rate	PSA complete response rate (PSA <0.2 ng/ml) in patient with mutations in DNA repair genes	1 Year
Secondary	PSA Complete Response Rate	PSA complete response rate (PSA <0.2 ng/ml) in patient without mutations in DNA repair genes	1 Year
Secondary	PSA Progression	Time to PSA progression	1 Year