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Prostate Cancer Biomarker Enrichment and Treatment Selection

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ClinicalTrials.gov Identifier: NCT03385655
Recruitment Status : Recruiting
First Posted : December 28, 2017
Last Update Posted : August 21, 2018
Sponsor:
Collaborators:
Canadian Cancer Clinical Trials Network
BC Cancer Foundation
Information provided by (Responsible Party):
Canadian Cancer Trials Group

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

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: AZD1775 Drug: Savolitinib Drug: Darolutamide Phase 2

Detailed Description:
This testing will be done on a samples of blood to see whether or not patients are eligible to take part in one of the main studies. Each study will be looking at what effects a new drug or drugs has on prostate cancer and will also be looking at the side effects of treatment. The purpose of the main studies is to see if the biomarkers that were identified screening samples can help predict which patients are most likely to be helped by that drug or drugs and to see how the cancer cells respond to treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: wee-I inhibitor Drug: AZD1775
300mg days 1-5, 8-12 q21 days

Experimental: cMET inhibitor Drug: Savolitinib
600mg once daily, orally.

Experimental: novel non-steroidal androgen receptor (AR) antagonist Drug: Darolutamide
600mg twice daily, orally.




Primary Outcome Measures :
  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. [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Measure effect of each study drug on PSA decline [ Time Frame: 2 years ]
  2. Measure objective response as determined by RECIST 1.1 criteria [ Time Frame: 2 years ]
  3. Number and severity of adverse events [ Time Frame: 2 years ]
  4. Measure effect of each study drug on time to PSA progression [ Time Frame: 2 years ]

Other Outcome Measures:
  1. To obtain cfDNA and non-malignant DNA from peripheral blood to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. [ Time Frame: 2 years ]
    obtain cfDNA from peripheral blood clinically annotated with patient disease characteristics and clinical follow-up data to identify potential predictive and prognostic factors. We will explore correlations between amount/concentration of cfDNA, germline and cfDNA somatic genomic aberrations with clinical outcomes such as response to subsequent treatment and overall survival.

  2. To obtain non-malignant DNA from peripheral blood to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. [ Time Frame: 2 years ]
    obtain non-malignant DNA from peripheral blood clinically annotated with patient disease characteristics and clinical follow-up data to identify potential predictive and prognostic factors. We will explore correlations between amount/concentration of cfDNA, germline and cfDNA somatic genomic aberrations with clinical outcomes such as response to subsequent treatment and overall survival.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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 differentiation.
  • Patients must consent to blood collection for testing after registration and prior to enrollment by a central reference laboratory.
  • To be eligible for screening patients must have received 0-1 regimen of cytotoxic therapy in the CRPC setting. Patients who have not received cytotoxic therapy for CRPC must have progressed since last regimen while patients who have received 1 regimen must have progressed during treatment or since coming off therapy.
  • Patients must have evidence of either biochemical or radiological disease progression in the setting of surgical or medical castration (i.e. have CRPC):
  • 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)
  • RECIST 1.1, or
  • PCWG3 Criteria for bone progression
  • Prior 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.
  • ECOG performance status 0 or 1 (Appendix I) and have a life expectancy of ≥ 6 months.
  • Patients must have clinically and/or radiologically documented disease (measurable or non-measurable as defined by RECIST 1.1. Patients with elevated PSA only are not eligible.
  • Patients must have received prior hormonal treatment with at least one of: abiraterone acetate, enzalutamide, apalutamide (ARN-509), darolutamide (ODM-201), TAK-700 and TOK-001 or other next-generation AR-pathway inhibitor (if agent is not listed, must be discussed and approved with CCTG prior to registration).
  • Prior strontium-89 at any time is not permitted.
  • Neutrophils ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 90 g/L; contact CCTG if hemoglobin is between 80-89 g/L, patient is not decompensated, is asymptomatic and transfusion is not indicated.
  • Bilirubin ≤ 1.5 ULN; if confirmed Gilbert's then bilirubin ≤ 3.0 x ULN
  • ALT ≤ 1.5 x ULN; if patient has liver metastases ≤ 5.0 x ULN
  • Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 45 mL/min; measured directly by 24-hour urine sampling OR as calculated by Cockcroft and Gault equation: Males: GFR = 1.23 x (140-age) x weight in kg/serum creatinine in μmol/L
  • Patient consent for screening must be appropriately obtained in accordance with applicable local and regulatory requirements.

Additional Criteria to be met prior to SUB-STUDY ENROLLMENT:

  • Patients must have recovered from any treatment-related toxicities prior to enrollment (unless ≤ grade 1, irreversible, or considered by investigator as not clinically significant).
  • Prior major surgery is permitted provided that a minimum of 14 days have elapsed between any major surgery and enrollment (7 days for minor surgery e.g. port insertion), and that wound healing has occurred.
  • Prior external beam radiation or radium-223 is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose and enrollment. Limited field radiation (for example less than 25% of marrow bearing bones) for palliation of bone pain is permitted < 2 weeks prior to starting study drug.
  • Prior systemic therapy is permitted as outlined below. Patients must have an have adequate washout prior to enrollment as follows and as specified in the Sections below:
  • Longest of one of the following:

    • Two weeks;
    • The longer of 30 days or 5 half-lives for investigational agents;
    • Standard cycle length of standard therapies.
  • Patients must have discontinued anti-androgens for at least 4 weeks prior to study entry (at least 6 weeks for bicalutamide).
  • 0-1 prior regimen of cytotoxic chemotherapy in the CRPC setting is permitted.
  • Systemic corticosteroids are permitted at a dose equivalent to <10 mg prednisone daily and are only permitted for reasons other than prostate cancer treatment (ex: fatigue, anorexia etc.); topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are permitted.
  • Bisphosphonates / denosumab are permitted for treatment of hypercalcemia, osteoporosis and skeletal-related events.
  • Patients must have adequate end-organ function and all laboratory tests must be performed within 7 days prior to enrollment.
  • Neutrophils ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin ≥ 90 g/L;
  • Bilirubin ≤ 1.5 ULN; if confirmed Gilbert's then bilirubin ≤ 3.0 x ULN
  • ALT ≤ 1.5 x ULN; if patient has liver metastases ≤ 5.0 x ULN
  • Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 45 mL/min; measured directly by 24-hour urine sampling OR as calculated by Cockcroft and Gault equation: Males: GFR = 1.23 x (140-age) x weight in kg/serum creatinine in μmol/L
  • Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
  • Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial.
  • Patients must agree to return to their primary care facility for any adverse events, which may occur through the course of the trial.
  • In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment.
  • Men of childbearing potential must have agreed to use a highly effective contraceptive method during Study Drug treatment and for 90 days after stopping treatment and should not father a child or donate sperm during this period.

Exclusion Criteria:

  • 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 ≥ 5 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 or chronic liver disease 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 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. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patients who have been treated with prior strontium-89 at any time or 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 skeletal-related events.
    • Warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), factor X inhibitors or fondaparinux is allowed.
    • Other anti-cancer or investigational agents (except LHRH)
  • History of hypersensitivity to any of the study drugs or any excipient.
  • Patients with a history of non-compliance to medical regimens.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03385655


Contacts
Contact: Francisco Vera-Badillo 613-533-6430 paco@ctg.queensu.ca

Locations
Canada, Alberta
Cross Cancer Institute Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Michael Kolinsky    780 432-8762      
Canada, British Columbia
BCCA - Vancouver Cancer Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Kim Chi    604 877-6000 ext 2746      
Canada, Nova Scotia
QEII Health Sciences Centre Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: Robyn J. Macfarlane    902 473-6106      
Canada, Ontario
London Regional Cancer Program Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Eric W. Winquist    519 685-8261      
Ottawa Hospital Research Institute Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Michael Ong    613 737-7700 ext 75051      
Canada, Quebec
CHUM-Centre Hospitalier de l'Universite de Montreal Recruiting
Montreal, Quebec, Canada, H2X 3E4
Contact: Fred Saad    514 890-8000 ext 27466      
Canada, Saskatchewan
Allan Blair Cancer Centre Recruiting
Regina, Saskatchewan, Canada, S4T 7T1
Contact: Muhammad Salim    306 766-2691      
Saskatoon Cancer Centre Recruiting
Saskatoon, Saskatchewan, Canada, S7N 4H4
Contact: Nayyer Iqbal    306 655-2710      
Sponsors and Collaborators
Canadian Cancer Trials Group
Canadian Cancer Clinical Trials Network
BC Cancer Foundation
Investigators
Study Chair: 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

Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT03385655     History of Changes
Other Study ID Numbers: I234
First Posted: December 28, 2017    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases