Histology-Independent Study of Palbociclib in Patients With Advanced Cancer

Study Overview
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Brief Summary
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The investigational drug being tested in this study is palbociclib. Palbociclib is considered experimental because it is not approved by the FDA for the treatment of all cancers. Palbociclib is currently approved for use in breast cancer. Palbociclib is a drug belonging to a family of drugs called kinase inhibitors. These drugs slow or stop the activity of particular proteins involved in the growth of human cells and in the abnormal growth of cancer cells. Blocking these proteins may decrease or stop tumor growth. The purpose of this study is to assess the safety of the study drug, to see how well it is tolerated, and also to find a safe dose range of the study drug in patients with specific kinds of tumor genetic changes.

Detailed Description
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This study proposes to give the cyclin dependent kinase (CDK) inhibitor palbociclib to patients with advanced malignancy harboring cyclin pathway aberrations (CCN/CDK alterations). The investigators study will determine whether cyclin signaling aberrations associate with response to this CDK inhibitor. Once completed, this study will identify subpopulations of patients that would best benefit from CDK inhibitor therapy with palbociclib and suggest directions for future study.

Official Title
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A Histology-Independent Study of the Cyclin Inhibitor Palbociclib in Patients With Advanced Cancer Harboring Aberrations in the Cyclin Pathway

Conditions
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Cancer, Advanced

Intervention / Treatment
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* Drug: Palbociclib 125mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Pathologically confirmed advanced or metastatic malignancy characterized by one or more of the following: Subject is intolerant to standard therapy Subject refuses standard therapy Malignancy is refractory to standard therapy Malignancy relapsed after standard therapy Malignancy for which there is no standard therapy that improves survival by at least 3 months. Evaluable tumor(s) with documented alteration(s) in CCN/CDK-related gene(s). The CCN/CDK aberration(s) can be identified at any point in the subject's cancer course. CCN/CDK testing must have been performed in a CLIA-certified laboratory. Amplification(s) and/or mutation frequencies will be defined according to the standard of the test used. ECOG Performance Status 0-2 Women of childbearing potential must have a negative baseline blood pregnancy test. Women and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study and for at least 30 days after discontinuation of study drug (the half life of palbociclib is about 27 hours in patients with cancer). Subjects must be off other anti-tumor agents for at least 5 half lives of the agent or 4 weeks from the last day of treatment, whichever is shorter. Endocrine therapies (for example for breast or prostate cancer) and anti-Her2 therapies (for example, trastuzumab or lapatinib) are allowed to continue while on this study. Subjects may not be receiving any other experimental agents. Ability to understand and willingness to sign a written consent document. Exclusion Criteria: Pregnant or lactating women. Subjects who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility. Recovery is defined as < Grade 2 severity per Common Terminology Criteria for Adverse Events Version 4.0(1) (CTCAE v4.0) or to their clinical baseline. Inability to swallow pills or determination by the investigator that absorption of oral medication would be impaired. Major surgery (not including placement of central lines) within 3 weeks prior to trial enrollment or planned surgery during the course of this study. Any medical condition which, in the opinion of the investigator, would preclude study participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single-center, open-label, non-randomized Phase II study of palbociclib in adult subjects with recurrent or refractory advanced cancers with aberration(s) in cyclin (CCN/CDK) signaling. Treatment will consist of daily oral administration of palbociclib in 28-day cycles.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palbociclib 125 mg<br>Palbociclib is administered orally at a starting dose of 125 mg/day for three weeks followed by one week off. Study measurements will be obtained at baseline and about every 8 weeks thereafter. Subjects will continue study drug until disease progression or unacceptable toxicity. | Drug: Palbociclib 125mg<br>* Palbociclib 125 mg is administered orally at a starting dose of 125 mg/day for three weeks followed by one week off. Study evaluations include physical exams, performance status, vital signs, laboratory blood tests, and radiographic or MRI imaging.<br>* Other names: Ibrance®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates in subjects with advanced cancer and aberrations of cyclin pathway gene(s) who are treated with palbociclib | Radiographic or MRI imaging will be assessed approximately every 8 weeks for disease progression. | Every 8 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Complete physical exams will be assessed every 2 to 4 weeks during treatment to evaluate the number of patients with a drug toxicity and disease progression. | Every 2-4 weeks from date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. | 
| Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | Laboratory blood tests will be assessed every 2 to 4 weeks during treatment to evaluate the number of patients for drug toxicity and disease progression. | Every 2-4 weeks from date of enrollment, assessed up to 36 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palbociclib, Cyclin Pathway, kinase inhibitor