Study Of Bosutinib With Capecitabine In Solid Tumors And Locally Advanced Or Metastatic Breast Cancer

NCT00959946 | Terminated Phase 1 Results

• 2 other identifiers: 3160A6-2208B1871011
• Study Type: interventional
• Target: 32
• Locations: 6 countries
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) - Part 1

  The MTD contour is defined as the dose combinations that achieve a toxicity rate (dose-limiting toxicity \[DLT\] rate) of less than (\<) 1/3. The observed toxicity rates for all the reporting groups (to which at least 1 cohort of participants was allocated) was estimated by calculating the proportion of DLTs observed in the first 21 days of treatment at those reporting groups. DLT includes grade (Gr) 3/4 nausea, vomiting, diarrhea, or asthenia more than 3 days, Gr 4 hematologic toxicities, delayed study treatment administration due to dose toxicities by more than 3 weeks. Pre-defined criterion for MTD: if a higher dose level of capecitabine existed such that the same dose level of bosutinib had a DLT rate of \<1/3, no MTD was recommended for that capecitabine dose and if even the lowest dose of bosutinib achieved a toxicity rate of greater than (\>) 1/3, no MTD was recommended for that capecitabine dose level.

  Part 1 Baseline up to Day 21

• Percentage of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) - Part 1

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  Part 1 Baseline up to 28 days after last dose of study treatment

• Percentage of Participants With Objective Response - Part 2

  Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR is defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions (LDs) of the target lesions taking as a reference the baseline sum LDs.

  Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose

Secondary Outcomes (11)

• Best Overall Response - Part 1

  Part 1 Baseline, every 6 weeks up to 6 months

• Progression Free Survival (PFS) - Part 2

  Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose

• Clinical Benefit Rate - Part 2

  Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose

• Duration of Response (DR) - Part 2

  Part 2 Baseline, every 6 weeks up to 2 to 6 weeks after last dose

• Maximum Observed Plasma Concentration (Cmax) - Part 2

  0 hour (Pre-dose) on Day 1 and 2, 3, 4, 6, 8 and 24 hours post-dose on Day 14 of Cycle 1

Study Arms (1)

1

EXPERIMENTAL

In part 1 (phase 1), ascending and descending multiple oral doses of bosutinib + capecitabine. Doses in part 1 include capecitabine 750 mg/m2 BID on days 1-14 + bosutinib 200 mg QD; capecitabine 625 mg/m2 BID on days 1-14 + bosutinib 300 mg QD. Depending on safety, capecitabine can also be administered at 1000 mg/m2 BID and bosutinib can be administered at 200 mg/m2 QD. The MTD of the combination treatment determined from part 1, will be administered in part 2 (phase 2).

Drug: Bosutinib; Drug: Capecitabine

Interventions

Bosutinib DRUG

Doses in part 1 include bosutinib 200 mg QD; bosutinib 300 mg QD. Depending on safety bosutinib can be administered at 200 mg/m2 QD. The MTD of the combination treatment determined from part 1, will be administered in part 2 (phase 2).

1

Capecitabine DRUG

Doses in part 1 include capecitabine 750 mg/m2 BID on days 1-14; capecitabine 625 mg/m2 BID on days 1-14. Depending on safety, capecitabine can also be administered at 1000 mg/m2 BID. The MTD of the combination treatment determined from part 1, will be administered in part 2 (phase 2).

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (7)

Pfizer Investigational Site

Boston, Massachusetts, 02114, United States

Location

Pfizer Investigational Site

Detroit, Michigan, 84202, United States

Location

Pfizer Investigational Site

Adelaide, South Australia, 5037, Australia

Location

Pfizer Investigational Site

Edegem, 2650, Belgium

Location

Pfizer Investigational Site

Saint-Herblain, 44805, France

Location

Pfizer Investigational Site

Hong Kong, Hong Kong

Location

Pfizer Investigational Site

Madrid, Madrid, 28050, Spain

Location

Related Publications (1)

• 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.

  PMID: 25290090 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

bosutinib; Capecitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Results are not provided because the study was terminated prior to part 2 due to unfavorable risk benefit ratio of the study treatment.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2009
• First Posted: August 17, 2009
• Study Start: September 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: February 22, 2013
• Results First Posted: February 22, 2013

Record last verified: 2013-01

Locations

ES (1); BE (1); FR (1); AU (1); HK (1); US (2)