Solid tumor and ErbB2 negative locally advanced or metastatic breast cancer MedDRA version: 12.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Part 1 only: Subjects with confirmed pathologic diagnosis of advanced breast cancer or pancreatic cancer or colorectal cancer or cholangiocarcinoma or glioblastoma that is not curable with available therapies, for whom bosutinib plus capecitabine is a reasonable treatment option. • Part 2 only: Subjects with confirmed pathologic diagnosis of locally advanced or metastatic breast cancer, or loco-regional recurrent breast cancer that is not amenable to curative treatment with surgery or radiotherapy. • Part 2 only: Documented ER+ and/or PgR+/erbB2- (Arm A only) or ER-/PgR-/erbB2- (Arm B only) tumor based on most recently analyzed biopsy, as documented by a local laboratory. • Part 2 only: Subjects must have received at least one but no more than 2 prior cytotoxic chemotherapy regimens for metastatic breast cancer. • Parts 1 & 2: At least 1 radiologically measurable lesion as defined by RECIST v1.0. • Part 2 only: Availability of formalin-fixed paraffin embedded (FFPE) tumor tissue block preferably or alternatively unstained slides for exploratory biomarker analysis. • Parts 1 & 2: Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Parts 1 & 2: Prior bosutinib, or any other prior Src inhibitor. • Part 1 only: Prior chemotherapy with capecitabine or 5-fluorouracil (5-FU) for the treatment of metastatic disease is allowed unless patient stopped therapy for toxicity (including but not limited to hand and foot syndrome, grade 3/4 diarrhea, etc). • Part 2 only: Prior chemotherapy with capecitabine or 5-FU for the treatment of metastatic disease. • Part 2 only: Prior chemotherapy with capecitabine or 5-FU for adjuvant chemotherapy within the past 12 months • Part 2 only: erbB2+ breast cancer • Parts 1 & 2: Cytotoxic chemotherapy, investigational therapy, major surgery or radiation therapy within 14 days of treatment day 1. • Parts 1 & 2: Bone or skin as the only site of disease. • Parts 1 & 2: Clinically unstable primary or metastatic central nervous system (CNS) tumors. Subjects with progression of CNS tumors are eligible as long as they have been clinically stable for at least 4 weeks prior to first dose of bosutinib and capecitabine (ie, no significant change in anticonvulsant or corticosteroid doses, mental status, or clinical symptoms). • Part 2 only: Any other cancer within 5 years before screening with the exception of adequately treated cervical cancer in situ, or adequately treated basal or squamous cell cancer of the skin. • Parts 1 & 2: Inadequate hepatic/renal/bone marrow function. • Parts 1 & 2: History of clinically significant or uncontrolled cardiac disease. • Parts 1 & 2: Serious concurrent illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For part 1, the primary objective is to assess the safety and tolerability, and to determine the MTD(s) of bosutinib plus capecitabine in patients with locally advanced or metastatic breast cancer or pancreatic cancer or colorectal cancer or cholangiocarcinoma or glioblastoma. For part 2, the primary objective is to determine the overall response rate (ORR) in women with ER+ and/or PgR+, erbB2- and ER-, PgR- erbB2- locally advanced or metastatic breast cancer. ;Primary end point(s): Overall Response Rate ORR is the proportion of subjects who achieve confirmed tumor response (complete or partial response) per RECIST v1.0. ;Secondary Objective: For part 1, the secondary objectives are to assess the preliminary anti-tumor activity for bosutinib plus capecitabine. For part 2, the secondary objective is to confirm the MTD(s) identified in part 1 by collecting further data on the safety and tolerability of bosutinib plus capecitabine, to evaluate the pharmacokinetics (PK) of bosutinib plus capeciatbine, to evaluate additional efficacy parameters such as progression-free survival, duration of response and clinical benefit rate (ORR+stable disease longer than 24 wks) | — |
Countries
Belgium, France, Hungary, Spain, United Kingdom
Outcome results
None listed