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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer

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Trial Information

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. 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.


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.

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Primary Purpose: Treatment

Outcome Measure:

To Determine the Adverse Events of PD0332991

Outcome Description:

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.

Safety Issue:

Yes

Authority:

United States: Food and Drug Administration

Study ID:

UPCC 02111

NCT ID:

NCT01320592

Start Date:

March 2011

Completion Date:

March 2013

Related Keywords:

  • Breast Cancer
  • 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
  • Breast Neoplasms

Name

Location

Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283