Safety Study of a New Schedule of Capecitabine and Docetaxel to Treat Cancers

NCT00169000 | Completed Phase 1 DMC

• 1 other identifier: D-0139
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The combination of capecitabine and docetaxel is given to treat several different types of cancer. Capecitabine is usually given by mouth for 14 days, and docetaxel is given IV on the first day of capecitabine. The effects of changes in the schedule of the combination of docetaxel and capecitabine has been examined in human breast cancer cells. A capecitabine by-product was given orally to breast cancer-bearing animals for 14 consecutive days. Docetaxel was given IV at a variety of times between days 1 and 15. The greatest reductions in the volume of the cancer were seen when animals were treated with docetaxel between days 6 and 10. In two other breast cancer models, the maximal degree of delay in growth of the tumors was achieved when the animals were treated with docetaxel on day 8 of a 14 day course of capecitabine. The extent of tumor response was not explained by changes in tumor levels of the enzyme thymidine phosphorylase, which is thought to be the mechanism behind the interaction of capecitabine and docetaxel. In the breast cancer cells, capecitabine increases the level of proteins which promote death of cancer cells, and it inhibits the levels of proteins which block death of cancer cells. Our hypothesis is that capecitabine and docetaxel interact with each other, because capecitabine primes the pro-death machinery of the cell by increasing the ratio of death-promoting proteins to death-inhibiting proteins. Cells are more susceptible to killing by docetaxel when the pro-death machinery is activated by capecitabine. This is a safety study to find the highest dose of capecitabine that can be given safely for 14 days, in combination with docetaxel given at a fixed dose on day 8. Once this dose of capecitabine has been determined, an additional nine patients with tumors that can be biopsied will be treated at this dose, and levels of capecitabine, its byproducts, and docetaxel will be measured in the bloodstream. Biopsies of tumors will also be taken before and after the docetaxel is given, and the levels of pro-death and anti-death proteins will be measured.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; capecitabine; docetaxel; pharmacokinetic/pharmacodynamic; bcl-2; bax

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose, and dose limiting toxicity of capecitabine when given daily for 14 days with docetaxel given on day 8 of a 21 day cycle

  3 weeks

Secondary Outcomes (3)

• To determine the pharmacokinetic profile of capecitabine, 5-fluorouracil, and 5'-deoxy-5-fluorouridine following administration of docetaxel on day 8.

  9 days

• To determine the expression of Bax, Bcl-2, and phosphorylated Bcl-2 at baseline and again on days 8 and 9 of capecitabine when given at the MTD

  9 days

• To define pharmacodynamic relationships between observed changes in dihydropyrimidine dehydrogenase (DPD) and altered expression of Bax and Bcl-2 with clinical toxicities and antitumor response

  9 days

Study Arms (1)

Capecitabine and Docetaxel

EXPERIMENTAL

Escalating doses of capecitabine days 1-14 with a fixed dose of docetaxel on Day 8 of a 21 day cycle

Drug: Capecitabine; Drug: Docetaxel

Interventions

Capecitabine DRUG

Capecitabine at the following dose levels for 14 days every 21 days, beginning with dose level 1 Dose level -2 600 mg/m2 po BID Dose level -1 700 mg/m2 po BID Dose level 1 825 mg/m2 po BID Dose level 2 1000 mg/m2 po BID

Also known as: Xeloda

Capecitabine and Docetaxel

Docetaxel DRUG

75 mg/m2 over one hour on day 8 of each cycle

Also known as: Taxotere

Capecitabine and Docetaxel

Eligibility Criteria

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

You may qualify if:

• Patients with a histologically or cytologically proven metastatic solid tumor.
• Patients with measurable disease or an evaluable bone lesion that will not undergo biopsy.
• Patients treated within the additional cohort at MTD will have metastatic breast cancer with a site of disease that is amenable to percutaneous FNA and must be willing to undergo serial FNA biopsies of their primary tumor.
• Age \> 18 years.
• Life expectancy of at least 6 months.
• ECOG performance status 0-2.
• Adequate hematologic, hepatic, and renal function
• Patients must have an intact upper gastrointestinal tract, be able to swallow tablets, and not have a malabsorption syndrome.

You may not qualify if:

• No significant uncontrolled infectious or cardiovascular disease, or a myocardial infarction within the prior 12 months.
• No prior organ allograft.
• No prior treatment with capecitabine or with docetaxel.
• No prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil.
• No concurrent antacid therapy is allowed.
• No other significant medical/surgical diseases.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Gary N Schwartz, MD

  Norris Cotton Cancer Center

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 15, 2005
• Study Start: January 1, 2003
• Primary Completion: September 1, 2005
• Study Completion: March 1, 2006
• Last Updated: August 6, 2009

Record last verified: 2009-08

Locations

US (1)