Histology-Independent Study of Palbociclib in Patients With Advanced Cancer

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

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.

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.

Inclusion Criteria:

1. Age ≥ 18 years old

2. 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.

3. 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.

4. ECOG Performance Status 0-2

5. 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).

6. 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.

7. Subjects may not be receiving any other experimental agents.

8. Ability to understand and willingness to sign a written consent document.

Exclusion Criteria:

1. Pregnant or lactating women.
2. 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.
3. Inability to swallow pills or determination by the investigator that absorption of oral medication would be impaired.
4. Major surgery (not including placement of central lines) within 3 weeks prior to trial enrollment or planned surgery during the course of this study.
5. Any medical condition which, in the opinion of the investigator, would preclude study participation