A Phase II Clinical Study on Efficacy of Palbociclib in Advanced Acral Melanoma With Cell Cycle Gene Aberrations
Overview
- Phase
- Phase 2
- Intervention
- Palbociclib
- Conditions
- Melanoma
- Sponsor
- Peking University Cancer Hospital & Institute
- Enrollment
- 60
- Primary Endpoint
- Overall response rate
- Last Updated
- 8 years ago
Overview
Brief Summary
It is a prospective, phase II, open-labeled, clinical trial aimed to determine the efficacy of palbociclib in advanced melanoma patients who bear gene aberrations in cell cycle pathways [including CDK4 amplification and/or CCND1 amplification and/or P16 (CDKN2A) loss]. Fifteen patients, if there is a response then further 45 patients will be enrolled. Totally 60 subjects with known above-mentioned gene aberrations who comply with the inclusion and exclusion criteria will be enrolled, their serum samples (at the time of the first administration of palbociclib and every 4 weeks afterwards) will be collected. Palbociclib will be given in the dose of 125 mg orally qd d1-21 every 28 days, unless disease progression or intolerance. All patients will be evaluated for the response to palbociclib by Response Evaluation Criteria in Solid Tumors (RECIST) at baseline. The standard radiographic imaging (CT scans) will be performed every 4 weeks until the end of treatment.
Detailed Description
This study is to evaluate efficacy of palbociclib in advanced acral melanoma patients with gene aberrations in cell cycle pathways \[including CDK4 amplification and/or CCND1 amplification and/or P16 (CDKN2A) loss\].
Investigators
Jun Guo
Director
Peking University Cancer Hospital & Institute
Eligibility Criteria
Inclusion Criteria
- •Age from 18 to 75 years;
- •ECOG performance status 0 or 1 before treatment;
- •Metastatic melanoma or unresectable acral melanoma;
- •Histologically confirmed melanoma.
- •Bearing gene aberrations in cell cycle pathways \[including CDK4 amplification and/or CCND1 amplification and/or P16 (CDKN2A) loss\].;
- •Anticipated life expectancy ≥ 3 month;
- •Adequate organ function, defined as following criteria:
- •Platelets 75 x 109/L, Hemoglobin 9.0 g/dL, Absolute Neutrophils(ANC) ≥ 1.5x109/L;
- •Serum bilirubin ≤ 1.5\*upper limit of normal (ULN) (could be ignored in the case of Gilbert's syndrome) ，Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 1.5 \* ULN;
- •Blood urea nitrogen (BUN) ≤ 1.5 \* ULN, serum creatinine (Cr) ≤ 1.5 \* ULN.
Exclusion Criteria
- •Previous or current administration of any kind of CDK4/6 inhibitors;
- •Administration of any other anti-tumor therapy (including but not limited to radiotherapy, chemotherapy, endocrinal therapy, surgery, molecular targeted therapy, immunotherapy or biological therapy) 4 weeks before inclusion; administration of mitocycin or nitrosamines 8 weeks before inclusion;
- •Non-treated brain metastasis (treatment controlled stable brain metastasis judged by investigators excluded);
- •Presence of third space fluid that cannot be controlled by drainage or other means (i.e. pleural effusion or ascites);
- •Long-term steroid therapy required;
- •Uncorrectable hypokalemia or hypomagnesaemia before inclusion;
- •Concurrent administration of drugs with potential of QT interval prolongation (such as antiarrhythmic drugs);
- •Allergies or previous history of severe allergies;
- •Active HBV or HCV infection (HBV viral copy number ≥ 104 copies/ml, HCV ≥ 103 copies/ml);
- •NCICTCAE Grade 2 toxicity before inclusion;
Arms & Interventions
Palbociclib
single arm
Intervention: Palbociclib
Outcomes
Primary Outcomes
Overall response rate
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
complete and partial response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Secondary Outcomes
- PFS(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- AE(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months)
- 6-month PFS rate(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months)