Clinical Trials /

Efficacy of Palbociclib in Advanced Acral Melanoma With Cell Cycle Gene Aberrations

NCT03454919

Description:

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.

Related Conditions:
  • Acral Lentiginous Melanoma
  • Melanoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy of Palbociclib in Advanced Acral Melanoma With Cell Cycle Gene Aberrations
  • Official Title: A Phase II Clinical Study on Efficacy of Palbociclib in Advanced Acral Melanoma With Cell Cycle Gene Aberrations

Clinical Trial IDs

  • ORG STUDY ID: 2017-003
  • NCT ID: NCT03454919

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
PalbociclibibrancePalbociclib

Purpose

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].
    

Trial Arms

NameTypeDescriptionInterventions
PalbociclibOthersingle arm
  • Palbociclib

Eligibility Criteria

        Inclusion Criteria:

          1. Age from 18 to 75 years;

          2. ECOG performance status 0 or 1 before treatment;

          3. Metastatic melanoma or unresectable acral melanoma;

          4. Histologically confirmed melanoma.

          5. Bearing gene aberrations in cell cycle pathways [including CDK4 amplification and/or
             CCND1 amplification and/or P16 (CDKN2A) loss].;

          6. Anticipated life expectancy ≥ 3 month;

          7. Adequate organ function, defined as following criteria:

               1. Platelets 75 x 109/L, Hemoglobin 9.0 g/dL, Absolute Neutrophils(ANC) ≥ 1.5x109/L;

               2. 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;

               3. Blood urea nitrogen (BUN) ≤ 1.5 * ULN, serum creatinine (Cr) ≤ 1.5 * ULN.

               4. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) as
                  assessed by multigated acquisition (MUGA) scan or echocardiography;

               5. QTc interval: male < 450msec, female < 470msec (via Fridericia method)

          8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

          9. Written informed consent signed.

        Exclusion Criteria:

          1. Previous or current administration of any kind of CDK4/6 inhibitors;

          2. 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;

          3. Non-treated brain metastasis (treatment controlled stable brain metastasis judged by
             investigators excluded);

          4. Presence of third space fluid that cannot be controlled by drainage or other means
             (i.e. pleural effusion or ascites);

          5. Long-term steroid therapy required;

          6. Uncorrectable hypokalemia or hypomagnesaemia before inclusion;

          7. Concurrent administration of drugs with potential of QT interval prolongation (such as
             antiarrhythmic drugs);

          8. Allergies or previous history of severe allergies;

          9. Active HBV or HCV infection (HBV viral copy number ≥ 104 copies/ml, HCV ≥ 103
             copies/ml);

         10. NCICTCAE Grade 2 toxicity before inclusion;

         11. Diagnosed as any second primary malignant tumor in 5 years before inclusion;

         12. Following conditions occur in the 6 months before drug administration: severe/
             unstable angina pectoris, myocardial infarction, congestive heart failure with
             symptoms, cerebrovascular accident, including transient ischemic attack, pulmonary
             embolism, ≥ grade II renal dysfunction, and other severe diseases that investigators
             judged to be unsuitable for this trial;

         13. Administration of potent CYP3A4 inhibitors in 7 days before inclusion , or
             administration of potent CYP3A4 inhibitors in 12 days before randomization ;

         14. NCICTCAE Grade ≥ 2 Active arrhythmias;

         15. Hypertension, defined as systolic blood pressure >150mmHg and/or diastolic blood
             pressure >100mmHg,and cannot be controlled by medication;

         16. No recommendation to receive >2 mg Warfarin treatment in 2 weeks before study
             beginning. It is permitted to use low dose Warfarin(<2 mg/3day) to prevent deep venous
             thrombosis. Low molecular weight heparin (fractionated) or aspirin are also allowed;

         17. Existence of any disease affecting drug absorption, including but not limited to: no
             ability to swallow oral medications, active inflammatory bowel disease, partial or
             complete obstruction, partial or total gastrectomy, extensive bowel resection or
             chronic diarrhea;

         18. Known infection of human immunodeficiency virus (HIV) or acquired immunodeficiency
             syndrome (AIDS)-related illness, or congenital immune deficiency diseases, organ
             transplantation history;

         19. Pregnancy, breastfeeding, childbearing age female who is reluctant to take effective
             contraceptive measures throughout trial period. All female patients with reproductive
             potential must have a negative pregnancy test (serum or urine) within 7 days before
             randomization and at first day of every cycle on visit.

         20. Other severe acute or chronic physiological or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study.

         21. Current treatment on another clinical trial. Supportive care or non-therapeutic
             clinical trials are allowed.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:complete and partial response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1

Secondary Outcome Measures

Measure:PFS
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
Safety Issue:
Description:Progression free survival
Measure:6-month PFS 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 6 months
Safety Issue:
Description:6-month PFS rate
Measure:AE
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
Safety Issue:
Description:adverse events

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Beijing Cancer Hospital

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