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.

Study Overview

• Status: Withdrawn
• Conditions: Cancer, Advanced
• Intervention / Treatment: Drug: Palbociclib 125mg

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Palbociclib 125 mg; 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; 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.; Other Names: Ibrance®

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Razelle Kurzrock, MD
• Investigators: Study Director: Scott Lippman, MD, UCSD

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2018
• Primary Completion (ANTICIPATED): February 1, 2020
• Study Completion (ANTICIPATED): February 1, 2024

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (ACTUAL): April 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: kinase inhibitor; Palbociclib; Cyclin Pathway
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Palbociclib
• Other Study ID Numbers: UCSD IIT 150729

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No