Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer

February 18, 2021 updated by: Abramson Cancer Center of the University of Pennsylvania

RATIONALE: PD 0332991 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects and how well PD 0332991 works in treating patients with refractory solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the response rates following treatment with PD 0332991 in the following malignancies: 1) Metastatic breast cancer, 2) Metastatic colorectal cancer, 3) Metastatic melanoma with CDK4 mutation or amplification, or 4) Cisplatin-refractory, unresectable germ cell tumors.

OUTLINE:

Patients receive oral PD 0332991 once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of unacceptable toxicity or disease progression.

Study Type

Interventional

Enrollment (Actual)

304

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

- Disease Characteristics:

All Subjects: All subjects treated under this protocol will have histologically documented cancer of one of the following types:

A. Metastatic breast cancer (7 triple negative, 23 ER+ after the first 15 patients are enrolled on the non-CCND1cohort; in addition 10 HER2+ for combination trastuzumab and PD0332991 therapy) up to 55 total enrollment slots B. Metastatic colorectal cancer that harbors the Kras or BRAF mutation (15-30 enrollment slots) C. Advanced or metastatic esophageal and/or gastric cancer (15-30 enrollment slots) D. Cisplatin-refractory, unresectable germ cell tumors (15-30 enrollment slots) E. Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other functional alteration at the G1/S checkpoint. (15-30 enrollment slots)

- Biopsy Requirements: For Subjects with accessible disease amenable to biopsy: A biopsy will be obtained pre-treatment and in during cycle 1 (while patient is receiving drug) for molecular markers of the cell cycle, and its inhibition.

  • Subjects will be > 18 years old
  • The subject has disease that is assessable by tumor marker, physical, or radiologic means.
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • The subject has adequate organ function, defined as follows A. Bilirubin ≤ 1.5 x the upper limit of normal (ULN) B. Serum creatinine ≤ 1.5 x UNL or calculated creatinine clearance ≥ 60 mL/min, and C. For subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN D. For subjects with liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase ≤ 5 x ULN
  • All tumors must test positive for Rb expression except:

A. ER positive metastatic breast tumors (data now shows all to be Rb positive.) B. Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation, CCND2 amplification OR any other functional alteration at the G1/S checkpoint.

- The subject has adequate marrow function, defined as follows: A. Absolute neutrophil count (ANC) >1500/mm3 B. Platelets >100,000/mm3, and C. Hemoglobin > 9 g/dL

  • The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document.
  • Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s).
  • Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months.
  • However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, or ovarian suppression.

Exclusion Criteria

  • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of PD 0332991. . Patients with HER2-overexpressing tumors may receive trastuzumab up to the date of starting therapy, and may continue to receive trastuzumab while receiving PD0332991.
  • The subject has received any other type of investigational agent within 28 days before the first dose of study treatment.
  • The subject has not recovered from clinically-meaningful toxicity due to prior therapy (i.e., back to baseline or Grade ≤ 1), with the exception of neurotoxicity and alopecia.
  • The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease unless the subject has a teratoma in which case s/he may be eligible if all other eligibility criteria are met

  • The subject has uncontrolled intercurrent illness including, but not limited to:

    1. ongoing or active infection
    2. diabetes mellitus
    3. hypertension
    4. symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
  • The subject has a baseline corrected QT interval (QTc) > 470 ms.
  • The subject is pregnant or breastfeeding.
  • The subject is known to be positive for the human immunodeficiency virus (HIV). Note:

baseline HIV screening is not required

- The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1 - Metastatic breast cancer

Metastatic breast cancer

PD-0332991 Given orally, 125 mg QD on a 21-day
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other Names:
  • Palbociclib
Experimental: Arm 2 - Metastatic colorectal cancer that harbors the Kras or BRAF mutation

Metastatic colorectal cancer that harbors the Kras or BRAF mutation

PD-0332991 Given orally, 125 mg QD on a 21-day
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other Names:
  • Palbociclib
Experimental: Arm 3 - Advanced or metastatic esophageal and/or gastric cancer

Advanced or metastatic esophageal and/or gastric cancer

PD-0332991 Given orally, 125 mg QD on a 21-day
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other Names:
  • Palbociclib
Experimental: Arm 4 - Cisplatin-refractory, unresectable germ cell tumors

Cisplatin-refractory, unresectable germ cell tumors

PD-0332991 Given orally, 125 mg QD on a 21-day
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other Names:
  • Palbociclib
Experimental: Arm 5 - CCND1amplification, CDK4/6mutation, CCND2amplification, OR other functional G1/S alterations

Any tumor type if tissue tests positive for CCND1 amplification, CDK4/6 mutation , CCND2 amplification OR any other functional alteration at the G1/S checkpoint.

PD-0332991 Given orally, 125 mg QD on a 21-day
Drug: PD-0332991
Given orally, 125 mg QD on a 21-day
Other Names:
  • Palbociclib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rates
Time Frame: 10 years

Response rates will be measured using the Response Evaluation Criteria in Solid Tumors (RECIST):

Complete Response (CR) - Disappearance of all target lesions Partial Response (PR) - ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline Progressive Disease (PD) - ≥20% increase in the sum of the longest diameter of the target lesions compared with the smallest sum of the longest diameter recorded since treatment started OR The appearance of 1 or more new lesions Stable Disease (SD) - Neither PR or PD Not Evaluable (NE)
10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center of the University of Pennsylvania

Investigators

  • Principal Investigator: Peter ODwyer, Abramson Cancer Center of the University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2009

Primary Completion (Actual)

October 1, 2019

Study Completion (Actual)

October 1, 2019

Study Registration Dates

First Submitted

December 10, 2009

First Submitted That Met QC Criteria

December 22, 2009

First Posted (Estimate)

December 23, 2009

Study Record Updates

Last Update Posted (Actual)

March 11, 2021

Last Update Submitted That Met QC Criteria

February 18, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 03909

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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