Carboplatin in Castration-resistant Prostate Cancer (PRO-PLAT)

Single Arm Open Label Phase II Pilot Study of Carboplatin in Patients With Metastatic Castrationresistant Prostate Cancer (CRPC) and PTEN Loss and/or DNA Repair Defects

Open label, non-randomised phase II clinical pilot study

Study Overview

• Status: Terminated
• Conditions: Prostatic Neoplasm
• Intervention / Treatment: Drug: Carboplatin

Detailed Description

Pilot Study of weekly Carboplatin in Patients with Advanced Metastatic Castration-Resistant Prostate Cancer (CRPC) and DNA repair defects

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Luzern, Switzerland
    • Luzern Cantonal Hospital
  • St.Gallen, Switzerland, 9007
    • Cantonal Hospital St.Gallen
  • Graubuenden
    • Chur, Graubuenden, Switzerland, 7000
      • Cantonal Hospital Chur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Written Informed Consent
2. Adult patients with histological diagnosis of adenocarcinoma of the prostate.
3. Metastatic Castration-Resistant Prostate Cancer (mCRPC)
4. Progression after at least one taxane-based chemotherapy (or contraindication against taxanes) and at least one therapy with a newer hormonal agent (Cyp17 inhibitor or a new generation AA like enzalutamide).
5. DNA repair defects as per central assessment
6. Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0 - 2

7. Progression of disease by any of the criteria listed here:

   • PSA utilizing PCWG 2 criteria
   • Bone scan
   • RECIST 1.1

8. Adequate organ and bone marrow function as evidenced by:

   • Haemoglobin ≥8.0 g/dL
   • Absolute neutrophil count ≥1.5 x 109/L
   • Platelet count ≥ 100 x 109/L
   • AST and/or ALT < 2.5 x ULN, in the presence of liver metastases: AST ≥5 x ULN, ALT <5 x ULN
   • Total bilirubin < 2.0 x ULN (except for patients with Gilbert's disease)
   • Creatinine Clearance ≥30ml/min
9. Patient must agree in the biomarker studies including the fresh tumour biopsies

Exclusion Criteria:

1. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product Carboplatin
2. Prior treatment with any prior platinum based chemotherapy,
3. Major surgery within 4 weeks prior to planned start of treatment
4. Known brain or leptomeningeal involvement unless clinically stable and on stable dose of steroids
5. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
6. Previous enrolment into the current study
7. Active secondary malignancy that requires systemic therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carboplatin; Carboplatin will be administered weekly	Drug: Carboplatin; Carboplatin will be administered weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	Soft tissue or PSA Response	Time Frame: Up to the end of the treatment phase (ie, approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of PSA declines of ≥30%	PSA	Time Frame: At 12 weeks and up to the end of the treatment phase (ie, approximately 6 months)
OS	Overall survival (OS) form start of Carboplatin	Time Frame: livelong follow-up
rPFS	Radiological progression-free survival (rPFS) from start of carboplatin	Time Frame: Up to the end of the treatment phase (ie, approximately 6 months
PSA	Time to PSA progression	on studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months
Safety as per CTC AEv4.03	Number of patients with adverse events	on studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months
Disease control rate	Disease control rate at 12 and 24 weeks (defined as SD, PR, CR, see response criteria	On studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months
PTEN loss	Evaluation of PTEN loss by FISH (Frequency and correlation with IHC)	Pre-study biopsy sample

Collaborators and Investigators

• Sponsor: Aurelius Omlin
• Collaborators: University Hospital, Zürich; Teva Pharma
• Investigators: Principal Investigator: Aurelius G Omlin, MD, Cantonal Hospital St. Gallen

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: December 2, 2014
• First Submitted That Met QC Criteria: December 5, 2014
• First Posted (Estimate): December 8, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Antineoplastic Agents; Carboplatin
• Other Study ID Numbers: CTU-14005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided