PD0332991/Paclitaxel in Advanced Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01320592
First received: March 16, 2011
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

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 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.


Condition Intervention Phase
Breast Cancer
Drug: PD0332991
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of PD0332991 and Paclitaxel in Patients With Rb-Expressing Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • To Determine the Adverse Events of PD0332991 [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Maximally Tolerated Dose in an expanded Cohort of Breast Cancer Patients [ Designated as safety issue: Yes ]
    To explore the activity of the combination at the MTD in an expanded cohort of breast cancer patients.

  • To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes [ Designated as safety issue: Yes ]
    To explore the relationship between selected biomarkers and efficacy, tolerability and safety outcomes


Estimated Enrollment: 20
Study Start Date: March 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
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 estalish 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 durationof patient participation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ECOG 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 UNL or calculated creatinine clearance > 60 mL/min, and for subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN

  • For subjects without extensive bone metastases: alkaline phosphatase levels < 2.5 x ULN.
  • For subjects with extensive bone metastases: alkaline phosphatase levels < 5 x ULN.
  • 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 medicatios on an ongoing basis.
  • Prior taxane therapy in the adjuvant or metastatic setting is allowed.
  • Concomitant use of biophosphonates 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320592

Contacts
Contact: Angela DeMichele, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Angela DeMichele, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Angela DeMichele, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01320592     History of Changes
Other Study ID Numbers: UPCC 02111
Study First Received: March 16, 2011
Last Updated: February 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
Patient must have histologically or cytologically-confirmed metastatic
breast cancer
Any ER, PR or Her2 status is allowed.
Tumor must express Retinoblastoma (Rb) protein, defined as
any measurable staining by immunohistochemistry on the invasive tumor component
<3 prior cyttoxic chemotherapy regimens for metastatic disease.
Performance status of 0-1 on the ECOG Performance Scale and life expectancy > 3 months.
Patient must have evaluable disease. Measureable disease is not required.
The subject has adequate organ function

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014