Clinical trial NCT00959946: Study Of Bosutinib With Capecitabine In Solid Tumors And Locally Advanced Or Metastatic Breast Cancer
Official title: A Phase 1/2, Open-Label Study Of Bosutinib Administered In Combination With Capecitabine In Subjects With Solid Tumor And ErbB2 Negative Locally Advanced Or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer (Parts 1 and 2)
Advanced Pancreatic Cancer (Part 1)
Advanced Colorectal Cancer (Part 1)
Advanced Cholangiocarcinoma (Part 1)
Advanced Glioblastoma Multiforme (Part 1)
Keywords: Phase 1/2
2-part study
bosutinib and capecitabine
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-08-17
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a research study in 2 parts assessing the following parameters of the combination of the study drug called bosutinib, and a drug called capecitabine: the safety, how well the subject's body handles the study drug, and preliminary anti-tumor activity as treatment for different types of cancers in part 1, and breast cancer only in part 2.

In part 1, subjects will receive bosutinib and capecitabine daily at different dose levels of each drug in order to determine the highest tolerated dose of the combination study treatment. In part 2, subjects will receive bosutinib and capecitabine at this highest tolerated dose to see how well the study treatment works to treat breast cancer. In addition, genetic research testing (research analyses involving genes and gene products) will be performed on biological samples from subjects.

Detailed description: The study was prematurely discontinued following Part 1 evaluation, when the sponsor concluded that further translational biomarker analyses were needed to better define the breast tumor biomarkers that predict sensitivity to Src family kinase inhibitors. Thus the Sponsor made a determination to stop the study after Part 1 as communicated to investigators on 02Dec2010 . No subjects were enrolled into Part 2 of this study. The study was not terminated due to safety reasons.

Eligibility criteria: Inclusion Criteria:

Part 1:

* Ages eligible for study: 18 years or older.
* Male and female.
* Confirmed pathologic diagnosis of advanced breast cancer or pancreatic cancer or colorectal cancer or cholangiocarcinoma or glioblastoma not curable with available therapies, for whom bosutinib plus capecitabine is a reasonable treatment option.

Part 2:

* Ages eligible for study: 18 years or older.
* Female.
* 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.
* Documented ER+ and/or PgR+/erbB2- or ER-/PgR-/erbB2- tumor based upon recently analyzed biopsy.

Exclusion Criteria:

Part 1:

* Prior bosutinib, or any other prior Src inhibitor.
* Prior chemotherapy with capecitabine or 5-FU for the treatment of metastatic disease is allowed unless patient stopped therapy for toxicity.

Part 2:

* Prior bosutinib, or any other prior Src inhibitor prior chemotherapy with capecitabine or 5-FU for the treatment of metastatic disease.
* Prior chemotherapy with capecitabine or 5-FU for adjuvant chemotherapy within the past 12 months.
* erbB2+ breast cancer.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) - Part 1
timeFrame: Part 1 Baseline up to Day 21
measure: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Part 1
timeFrame: Part 1 Baseline up to 28 days after last dose of study treatment
measure: Percentage of Participants With Objective Response - Part 2
timeFrame: Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose
Secondary outcomes:
measure: Best Overall Response - Part 1
timeFrame: Part 1 Baseline, every 6 weeks up to 6 months
measure: Progression Free Survival (PFS) - Part 2
timeFrame: Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose
measure: Clinical Benefit Rate - Part 2
timeFrame: Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose
measure: Duration of Response (DR) - Part 2
timeFrame: Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose
measure: Maximum Observed Plasma Concentration (Cmax) - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
measure: Apparent Volume of Distribution (Vz/F) - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
measure: Apparent Oral Clearance (CL/F) - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
measure: Terminal-Phase Disposition Rate Constant (λz) - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
measure: Plasma Decay Half-Life (t1/2) - Part 2
timeFrame: 0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1
Other outcomes:
Locations:
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Adelaide
country: Australia
facility: Pfizer Investigational Site
state: South Australia
city: Edegem
country: Belgium
facility: Pfizer Investigational Site
city: Saint Herblain
country: France
facility: Pfizer Investigational Site
city: Hong Kong
country: Hong Kong
facility: Pfizer Investigational Site
city: Madrid
country: Spain
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Isakoff SJ, Wang D, Campone M, Calles A, Leip E, Turnbull K, Bardy-Bouxin N, Duvillie L, Calvo E. Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study. Br J Cancer. 2014 Nov 25;111(11):2058-66. doi: 10.1038/bjc.2014.508. Epub 2014 Oct 7.