| Titre |
Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study |
| Protocole ID |
IND.234 |
| ClinicalTrials.gov ID |
NCT03385655 |
| Type(s) de cancer |
Prostate |
| Phase |
Phase II |
| Institution |
CENTRE HOSPITALIER DE L'UNIVERSITE DE MONTREAL
|
| Ville |
Montréal |
| Investigateur(trice) principal(e) |
Dr Fred Saad
|
| Coordonnateur(trice) |
Amal Nadiri
514-890-8000 poste 26074
|
| Statut |
 Actif en recrutement |
| Critètes d'éligibilité |
- 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.
|
| Critètes d'exclusion |
- 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.
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Groupe d'étude en oncologie du Québec