Prostate Cancer Biomarker Enrichment and Treatment Selection

NCT03385655 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: I234
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of the pre-study screening is to test for DNA abnormalities or biomarkers.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate defined as proportion of patients who had PSA decline ≥ 50%, complete or partial objective response, or Stable disease for ≥ 12 weeks.

  2 years

Secondary Outcomes (6)

• Measure effect of each study drug on PSA decline

  2 years

• Measure objective response as determined by RECIST 1.1 criteria

  2 years

• Number and severity of adverse events

  2 years

• Measure effect of each study drug on time to PSA progression

  2 years

• To summarize progression-free survival

  2 years

Study Arms (7)

WEE-1 inhibitor - ARM CLOSED

EXPERIMENTAL

Drug: Adavosertib

cMET inhibitor

EXPERIMENTAL

Drug: Savolitinib

novel non-steroidal androgen receptor (AR) antagonist

EXPERIMENTAL

Drug: Darolutamide

CFI400945 PLK4 inhibitor - ARM CLOSED

EXPERIMENTAL

Drug: CFI-400945

Ipatasertib AKT inhibitor

EXPERIMENTAL

Drug: Ipatasertib

Durvalumab and Tremelimumab immunotherapy

EXPERIMENTAL

Drug: Durvalumab and Tremelimumab

Carboplatin platinum based chemotherapy

EXPERIMENTAL

Drug: Carboplatin

Interventions

Adavosertib DRUG

250mg, may dose escalate to 300mg if no drug-related GI tox in cycle 1

WEE-1 inhibitor - ARM CLOSED

Savolitinib DRUG

600mg once daily, orally.

cMET inhibitor

Darolutamide DRUG

600mg twice daily, orally.

novel non-steroidal androgen receptor (AR) antagonist

CFI-400945 DRUG

Dose level assigned at enrollment, starting at 32mg/day on Days 1-7 and 15-21 or 15-28 depending on toxicity experienced.

CFI400945 PLK4 inhibitor - ARM CLOSED

Ipatasertib DRUG

400mg daily 3 weeks on, 1 week off

Ipatasertib AKT inhibitor

Durvalumab and Tremelimumab DRUG

Durvalumab 1500mg day 1 every 4 weeks; Tremelimumab 225mg day 1 cycle 1

Durvalumab and Tremelimumab immunotherapy

Carboplatin DRUG

AUC 5 IV 60min Day 1 q 21 days

Carboplatin platinum based chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following will be required prior to REGISTRATION:
• Patients must have histologically confirmed adenocarcinoma of the prostate without pathologic or clinical evidence (e.g. PSA \< 2.0 μg/L with liver metastases) of small cell neuroendocrine differentiation.
• Patients must consent prior to blood collection for screening correlative testing by a central reference laboratory. The screening blood sample cannot be sent for analysis prior to screening registration.
• All patients must have consented to the release of a tumour block from their primary or metastatic tumour. The centre/pathologist must have agreed to the submission of the specimen(s). Contact CCTG if no archival tissue is available.
• Patients must have evidence of castrate resistance with either biochemical or radiological disease progression in the setting of surgical or medical castration:
• PSA Progression:
• Minimum of two rising PSA values from a baseline measurement with an interval of ≥ 1 week between each measurement
• PSA must be ≥ 2.0 µg/L (ng/mL)
• Objective progression:
• RECIST 1.1, or
• PCWG3 Criteria for bone progression
• Surgical/Medical Castration:
• Prior bilateral orchiectomy, or
• LHRH agonist/antagonist and testosterone \< 50 ng/dL or \< 1.7 nmol/L. LHRH agonist/antagonist therapy must be maintained for the duration of study therapy and if previously discontinued, must be restarted and castrate level of testosterone present.
• Patients must be ≥18 years of age.

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, or other solid tumours curatively treated with no evidence of disease for ≥ 2 years.
• Patients with central nervous system (CNS) involvement unless at least 4 weeks from prior therapy completion (including radiation and/or surgery) AND clinically stable and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases. Patients with epilepsy not due to CNS metastases are eligible as long as no contraindication or concern with drug interactions.
• Patients with serious illnesses or medical conditions which could cause unacceptable safety risks or would not permit the patient to be managed according to the protocol. This includes but is not limited to:
• active infection requiring systemic therapy;
• active or known human immunodeficiency virus (HIV) with detectable viral load;
• uncontrolled or recent clinically significant cardiac disease, including:
• angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months;
• history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy;
• history of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months;
• patients with uncontrolled hypertension.
• Patients with significant liver diseases including viral/other hepatitis, current alcohol abuse or cirrhosis.
• Patients who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. Crohn's disease, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, active bowel inflammation (e.g. diverticulitis) or small bowel resection), unless agreed with CCTG (exceptions may be given if parenteral substudy is available/appropriate.
• Patients who require continued or concurrent treatment with:
• Systemic corticosteroids at a dose equivalent to prednisone \> 10 mg daily. Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed.
• Bisphosphonates / denosumab for reasons other than hypercalcemia, osteoporosis or prevention of skeletal-related events.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Canadian Cancer Clinical Trials Network: collaborator
• BC Cancer Foundation: collaborator

Study Sites (11)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (1)

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

  PMID: 32203306 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

adavosertib; 1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine; darolutamide; 2-(3-(4-((2,6-dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5'-methoxyspiro(cyclopropane-1,3'-indolin)-2'-one; ipatasertib; durvalumab; tremelimumab; Carboplatin

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

Study Officials

• Michael Kolinsky

  Cross Cancer Institute, Edmonton, AB Canada

  STUDY CHAIR

• Som Mukherjee

  Juravinski Cancer Centre at Hamilton Health Sciences Centre, ON Canada

  STUDY CHAIR

• Michael Ong

  Ottawa Hospital Research Institute, Ottawa, ON Canada

  STUDY CHAIR

• Kim Chi

  BCCA - Vancouver Cancer Centre

  STUDY CHAIR

• Aaron Hansen

  University Health Network, Toronto, ON, Canada

  STUDY CHAIR

• Sebastien Hotte

  Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

  STUDY CHAIR

• Zineb Hamilou

  CHUM-Centre Hospitalier de l'Universite de Montreal

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2017
• First Posted: December 28, 2017
• Study Start: August 1, 2018
• Primary Completion: October 7, 2024
• Study Completion: December 31, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)