Groupe d'Etude en Oncologie du Quebec

Titre	A Phase II Study of Palbociclib, A CDK4/6 Inhibitor, in Patients With Metastatic Castration-Resistant Prostate Cancer
Protocole ID	IND.223
ClinicalTrials.gov ID	NCT02905318
Type(s) de cancer	Prostate
Phase	Phase II
Type étude	Traitement
Médicament	Palbociclib
Institution	CIUSSS DU CENTRE-OUEST-DE-L'ILE-DE-MONTREAL HOPITAL GENERAL JUIF SIR MORTIMER B.DAVIS 3755 rue de la Côte Ste. Catherine, Montréal, QC, H3T 1E2
Ville	Montréal
Investigateur(trice) principal(e)	Dr Cristiano Ferrario
Coordonnateur(trice)
Statut	Actif en recrutement
Date d'activation	19-10-2017
Critètes d'éligibilité	Patients must have histologically confirmed adenocarcinoma of the prostate without evidence of small cell/neuroendocrine differentiation. Patients must consent to blood collection and be screened for CCND1 gain/amplification and RB1 status prior to enrolment by a central reference laboratory. Patients must have clinically and/or radiologically documented disease. Patients with elevated PSA only are not eligible. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative). Patients must have evidence of 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 ug/L Objective progression: RECIST 1.1 or Soft tissue or visceral disease progression or Bone progression (>2 new lesions on bone scan or CT) Surgical/medical castration: 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. Previous Therapy: Patients must have recovered from any treatment-related toxicities prior to registration (unless ≤ grade 1, irreversible, or considered by investigator as not clinically significant). Surgery: Prior major surgery is permitted provided that a minimum of 14 days have elapsed between any major surgery and registration, and that wound healing has occurred. Radiation: Prior external beam radiation or radium-223 is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose and registration. 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 strontium-89 at any time is not permitted. Systemic Therapy: Prior systemic therapy is permitted as outlined below. Patients must have recovered from all reversible toxicity related to prior systemic therapy and have adequate washout prior to registration 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. Hormonal Therapy: Patients must have received prior hormonal treatment with at least one of abiraterone acetate, enzalutamide, ARN-509 TAK-700 and TOK-001. Prior anti-androgen therapy must have been discontinued at least 28 days (or 42 days for bicalutamide) prior to registration. Cytotoxic Therapy: A maximum of one prior regimen of cytotoxic chemotherapy is permitted. Prior treatment with docetaxel, cabazitaxel and mitoxantrone is permitted. Immunotherapy: Patients may have received prior immunotherapy; vaccines and treatment with oncolytic viruses is permissible. Other therapy: Previous therapy with CDK or mTOR inhibitors is not allowed. Prior treatment with other agents, such as tyrosine kinase or other targeted agents is permissible. Systemic corticosteroids are permitted at a dose equivalent to <10 mg prednisone daily; 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. Laboratory Requirements: Neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥ 100 g/L Bilirubin ≤ 1.5 x ULN; if confirmed Gilbert's then bilirubin ≤ 3.0 x ULN AST and ALT ≤ 1.5 x ULN; if patient has liver metastases ≤ 5.0 x ULN Serum creatinine ≤ 1.5 x ULN or Creatinine clearance ≥ 50 mL/min; Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient registration. Men of childbearing potential must have agreed to use a highly effective contraceptive method during 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 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; uncontrolled/severe cardiovascular disease active or known human immunodeficiency virus (HIV); 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 with history of hypersensitivity to palbociclib or any of its excipients. Patients who have been treated with prior CDK4/6 inhibitors, mTOR inhibitors or 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. Any medications or substances that are potent/strong inhibitors or inducers of CYP3A isoenzymes. All patients must have discontinued these medications at least 7 days prior to the first dose of protocol treatment (at least 14 days for herbal/dietary supplements and traditional Chinese medicines). 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) Patients with a history of non-compliance to medical regimens.

Groupe d'étude en oncologie du Québec