Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prostate Cancer Biomarker Enrichment and Treatment Selection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03385655
Recruitment Status : Recruiting
First Posted : December 28, 2017
Last Update Posted : March 30, 2020
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: Adavosertib Drug: Savolitinib Drug: Darolutamide Drug: CFI-400945 Drug: Ipatasertib Drug: Durvalumab and Tremelimumab 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.

Layout table for study information
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, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: WEE-1 inhibitor Drug: Adavosertib
300mg days 1-5, 8-12 q21 days

Experimental: cMET inhibitor Drug: Savolitinib
300mg once daily, orally.

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

Experimental: CFI400945 PLK4 inhibitor Drug: CFI-400945
Dose level assigned at enrollment on 1 wk on and 1 wk off. Cycle 1 will consist of a 14-day run-in with CFI-400945 at 48 mg/day for 7 days and followed by a 7-day period without CFI-400945 administration.

Experimental: Ipatasertib AKT inhibitor Drug: Ipatasertib
400mg daily 3 weeks on, 1 week off

Experimental: Durvalumab and Tremelimumab immunotherapy Drug: Durvalumab and Tremelimumab
Durvalumab 1500mg day 1 every 4 weeks; Tremelimumab 225mg day 1 cycle 1




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 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.
  • ECOG performance status 0 or 1 (Appendix I) and have a life expectancy of ≥ 6 months.
  • Patients must have radiologically documented disease (measurable or non-measurable as defined by RECIST 1.1. Patients with elevated PSA only are not eligible.
  • 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.
  • Serum potassium within normal limits
  • Bilirubin ≤ 1.5 ULN; if confirmed Gilbert's then bilirubin ≤ 3.0 x ULN
  • ALT ≤ 2.5 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 and subsequent enrollment (as applicable) must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to screening and subsequent enrollment (as applicable) in the trial to document their willingness to participate.

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. Exceptions may be made for low-dose non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiation is not permitted. Prior strontium-89 at any time is not permitted.
  • Previous Hormone Therapy: 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). Consult substudies for additional criteria
  • Prior cytotoxic therapy: Patients may have received cytotoxic therapy in the castrate sensitive setting as well as up to 1 regimen of cytotoxic therapy in the CRPC setting
  • Patients must have an adequate washout prior to enrollment as follows:
  • Longest of one of the following:

    • Standard cycle length of standard therapies;
    • Two weeks;
    • The longer of 30 days or 5 half-lives for investigational agents;
  • Patients must have discontinued anti-androgens for at least 4 weeks prior to substudy entry/enrollment (at least 6 weeks for bicalutamide).
  • LHRH agonist therapy must continue unless surgically castrated. Note: after discussion, CCTG selected patients may be screened prior to adequate washout.
  • Patient must have progressed (biochemically or radiologically, as defined in 4.1.4) during or after their last systemic therapy
  • Patients must be accessible for treatment and follow up. Patients registered enrolled 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.
  • Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, response assessment and follow-up.
  • 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 for 6 months after stopping treatment and should not father a child or donate sperm during this period.
  • In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy / vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he is responsible for beginning contraceptive measures.

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 ≥ 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.
    • 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.
  • Patients who have received growth factors within 28 days prior to initiation of dosing of study drug or who are likely to require treatment with growth factors throughout the duration of the trial.

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
Layout table for location contacts
Contact: Lesley Seymour 613-533-6430 lseymour@ctg.queensu.ca

Locations
Layout table for location information
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
Juravinski Cancer Centre at Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Som Mukherjee    905 387-9495 ext 64605      
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      
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Adrian Sacher    416 946-4501 ext 3550      
Canada, Quebec
CHUM-Centre Hospitalier de l'Universite de Montreal Recruiting
Montreal, Quebec, Canada, H2X 3E4
Contact: Fred Saad    514 890-8000 ext 27466      
The Jewish General Hospital Suspended
Montreal, Quebec, Canada, H3T 1E2
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
Layout table for investigator information
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
Study Chair: Aaron Hansen University Health Network, Toronto, ON, Canada
Study Chair: Sebastien Hotte Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

Layout table for additonal information
Responsible Party: Canadian Cancer Trials Group
ClinicalTrials.gov Identifier: NCT03385655    
Other Study ID Numbers: I234
First Posted: December 28, 2017    Key Record Dates
Last Update Posted: March 30, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Durvalumab
Tremelimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents