PD0332991/Paclitaxel in Advanced Breast Cancer

April 7, 2020 updated by: Abramson Cancer Center of the University of Pennsylvania

A Phase 1 Trial of PD0332991 and Paclitaxel in Patients With Rb-Expressing Advanced Breast Cancer

This study is a phase I, single arm, open-label trial of PD0332991 in combination with Paclitaxel in patients with Rb-expressing metastatic breast cancer. Up to 20 patients are anticipated to be enrolled to reach the Maximum Tolerated Dose (MTD) of PD0332991 in combination with Paclitaxel. Once the MTD is established, an additional expanded cohort of 10 patients will be enrolled at that dose to establish the Recommended Phase 2 Dose (RP2D), obtain additional safety data and perform exploratory biomarker studies.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study is a phase I, single arm, open-label trial of PD0332991 in combination with paclitaxel in patients with Rb-expressing metastatic breast cancer. Patients will be treated as shown in the schema below. Up to 20 patients are anticipated to be enrolled to reach the MTD of PD0332991 in combination with Paclitaxel. Once the MTD is established, an additional expanded cohort of 10 patients will be enrolled at that dose to establish the RP2D, obtain additional safety data and perform exploratory biomarker studies. The primary endpoint will be assessed after one cycle of therapy. Patients will remain on study until dose limiting toxicity, disease progression or physician/patient discretion. Safety assessment will continue for the duration of patient participation.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 1

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

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient must have histologically or cytologically-confirmed metastatic breast cancer. Any ER, PR or Her2 status is allowed.
  • Tumor must express Retinoblastoma (Rb) protein, as defined as any measureable staining by immunohistochemistry
  • Male or female and > 18 years of age on the day of signing informed consent.
  • Patient must have received < prior cytotoxic regimens for metastatic breast cancer. This does not include cytoxic regimens used in the adjuvant setting.
  • Performance status of 0-1 on the Eastern Cooperative Oncology Group Performance Scale and life expectancy > 3 months.
  • patient on the dose-escalation portion of the trial must have evaluable disease, defined as either measurable (by RECIST) or non-measurable disease (e.g. bone mets, pleural effusion or lymphangitic spread). Measurable disease is required for patients in the expanded RP2D cohort.
  • The subject must have adequate organ function, defined as follows:

Bilirubin < 1.5 x upper normal limit or calculated creatinine clearance > 60 mL/min, and for subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper normal limit

  • For subjects without extensive bone metastases: alkaline phosphatase levels < 2.5 x upper normal limit .
  • For subjects with extensive bone metastases: alkaline phosphatase levels < 5 x upper normal limit .
  • The subject must have adequate marrow function, defined as follows
  • Absolute neutrophil count (ANC) >1500/mm
  • Platelets > 100,000/mm
  • Hemoglobin > 9 g/dL
  • Female patient of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication and agree to the use of effective methods of contraception while on study.
  • Patient must be capable of, and must voluntarily agree to participate by giving written informed consent.
  • Patient must be able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis.
  • Prior taxane therapy in the adjuvant or metastatic setting is allowed.
  • Concomitant use of biphosphonates is allowed.
  • Patients with stable, treated CNS disease are eligible.

Exclusion Criteria:

  • Patient who has had chemotherapy, radiotherapy or hormonal therapy within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab), or who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day 1. If the patient has residual toxicity from prior treatment, toxicity must be < Grade 1.
  • patients less than 4 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia.
  • Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases (including brain metastases) who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. Oral corticosteroids for control of CNS symptoms are allowed.
  • Patient has known hypersensitivity to the components of study drug or its analogs.
  • The subject has uncontrolled intercurrent illness including, but not limited to Ongoing or active infection
  • Diabetes mellitus
  • Hypertension
  • Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months.
  • Patient has baseline neuropathy of > grade 2
  • Patients who have known allergic reactions to Paclitaxel or IV Contrast Dye despite standard prophylaxis.
  • 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 eor 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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: PD0332991 and Paclitaxel
PD0332991 in combination with weekly paclitaxel at a fixed dose of 80 mg/m2
Drug: Paclitaxel
Drug: PD0332991

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To Determine the Adverse Events of PD0332991
Time Frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days) .
To determine the maximally-tolerated dose and safety of PD0332991 in combination with a fixed, weekly dose of Paclitaxel of 80 mg/m2 and to characterize the safety of the combination during the first three cycles of therapy.
weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days) .

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximally Tolerated Dose in an expanded Cohort of Breast Cancer Patients
Time Frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
To explore the activity of the combination at the MTD in an expanded cohort of breast cancer patients.
weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes
Time Frame: weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)
To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes
weekly paclitaxel at a fixed dose of 80 mg/m2 and to assess the safety of the combination after 3 cycles of therapy (cycles are 28 days)

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

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 (ACTUAL)

March 1, 2011

Primary Completion (ACTUAL)

May 1, 2019

Study Completion (ACTUAL)

May 1, 2019

Study Registration Dates

First Submitted

March 16, 2011

First Submitted That Met QC Criteria

March 21, 2011

First Posted (ESTIMATE)

March 22, 2011

Study Record Updates

Last Update Posted (ACTUAL)

April 8, 2020

Last Update Submitted That Met QC Criteria

April 7, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 02111

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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