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 : January 5, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Drug: Adavosertib Drug: Savolitinib Drug: Darolutamide Drug: CFI-400945 Drug: Ipatasertib Drug: Durvalumab and Tremelimumab Drug: Carboplatin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||600 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study|
|Actual Study Start Date :||December 12, 2017|
|Estimated Primary Completion Date :||July 31, 2023|
|Estimated Study Completion Date :||July 31, 2024|
|Experimental: WEE-1 inhibitor - ARM CLOSED||
250mg, may dose escalate to 300mg if no drug-related GI tox in cycle 1
|Experimental: cMET inhibitor||
600mg once daily, orally.
|Experimental: novel non-steroidal androgen receptor (AR) antagonist||
600mg twice daily, orally.
|Experimental: CFI400945 PLK4 inhibitor - ARM CLOSED||
Dose level assigned at enrollment, starting at 32mg/day on Days 1-7 and 15-21 or 15-28 depending on toxicity experienced.
|Experimental: Ipatasertib AKT inhibitor||
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
|Experimental: Carboplatin platinum based chemotherapy||
AUC 5 IV 60min Day 1 q 21 days
- 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 ]
- Measure effect of each study drug on PSA decline [ Time Frame: 2 years ]
- Measure objective response as determined by RECIST 1.1 criteria [ Time Frame: 2 years ]
- Number and severity of adverse events [ Time Frame: 2 years ]
- Measure effect of each study drug on time to PSA progression [ Time Frame: 2 years ]
- To summarize progression-free survival [ Time Frame: 2 years ]
- To summarize overall survival [ Time Frame: 2 years ]
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.
|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|
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:
- 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 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. Consult CCTG if patients have received other therapeutic radioisotopes. Exceptions may be made for low-dose non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiation is not permitted. If radiation is required for example for pain control, it must be completed prior to enrollment. 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.
- 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.
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
|Contact: Lesley Seymouremail@example.com|
|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|
|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: Di (Maria) Jiang 647 993-0448|
|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||Recruiting|
|Montreal, Quebec, Canada, H3T 1E2|
|Contact: Cristiano Ferrario 514 398-8307|
|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|
|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|
|Study Chair:||Zineb Hamilou||CHUM-Centre Hospitalier de l'Universite de Montreal|
|Responsible Party:||Canadian Cancer Trials Group|
|Other Study ID Numbers:||
|First Posted:||December 28, 2017 Key Record Dates|
|Last Update Posted:||January 5, 2023|
|Last Verified:||January 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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