A Phase I Trial of Capecitabine in Combination With Gemcitabine and Erlotinib for Advanced Pancreatic Cancer

NCT00480584 | Completed Phase 1 DMC

• 2 other identifiers: MCC-14624OSI3482s
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I clinical trial examining the safety, feasibility, and toxicity of gemcitabine and erlotinib when given in combination with capecitabine in adult patients with locally advanced unresectable or metastatic pancreatic adenocarcinoma. Treatment will be administered at Moffitt on an outpatient basis and consists gemcitabine once per week for 3 weeks, followed by a week off treatment. Erlotinib (tablet) taken by mouth continuously starting with day one of cycle 1 with capecitabine taken twice per day on days 1-14 of each cycle followed by a 2 week off treatment rest period. An accelerated dose-escalation scheme will be employed with 4 planned dose levels. Whenever patients have been enrolled at a given dose with at most 1 DLT, the protocol will be stopped and the dose will be called the maximum tolerated dose (MTD). Patients will be treated at the recommended phase II dose (RPTD) to confirm tolerability at that dose. In the absence of treatment delays due to adverse events, treatment may continue for 6 cycles or until disease progression and patients may continue on the study regimen unless they experience an adverse event that meets the criteria for a dose limiting toxicity.

Conditions

Metastatic Pancreatic Carcinoma

Keywords

pancreatic; gemcitabine; erlotinib (HER1/epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor); capecitabine

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The Maximum-tolerated dose (of capecitabine) is determined as the dose level at which two or more of six patients experience dose-limiting toxicity. The MTD will not exceed 1250 mg/m2.

  Within 4 months of Cycle 1 Day 1 (C1D1)

Secondary Outcomes (1)

• Recommended Phase II Dose (RPTD)

  Within 4 months of Cycle 1 Day 1 (C1D1)

Study Arms (1)

GemCap-T Dose Escalation

EXPERIMENTAL

GemCap-T, capecitabine in combination with gemcitabine. Dose Escalation 6 Cycles @ 28 Days.

Drug: gemcitabine; Drug: capecitabine; Drug: erlotinib

Interventions

gemcitabine DRUG

Levels 1 through 4: 1000 mg/m\^2

Also known as: Gemzar®

GemCap-T Dose Escalation

capecitabine DRUG

Level 1: 500 mg/m\^2; Level 2: 825 mg/m\^2; Level 3: 1000 mg/m\^2; Level 4: 1250 mg/m\^2

Also known as: Xeloda

GemCap-T Dose Escalation

erlotinib DRUG

Levels 1 through 4: 100 mg

Also known as: Tarceva®

GemCap-T Dose Escalation

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed pancreatic adenocarcinoma that is metastatic or unresectable.
• Previously untreated with chemotherapy in the metastatic setting. Prior 5-fluorouracil (5-FU) or capecitabine treatment is allowed if: 1) it was given as part of a combined modality chemoradiation regimen and 2) no greater than 30% of bone marrow was included in the field and 3) the treatment free interval has been \> 6 weeks
• Must have measurable disease, defined as at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Age greater than or equal to 18 years
• Because no dosing or adverse event data are currently available on the use of capecitabine in combination with gemcitabine and erlotinib in patients \<18 years of age, children are excluded from this study. Pancreatic adenocarcinoma is primarily a disease of the elderly.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 2 (Karnofsky greater than or equal to 60%).
• Life expectancy \> 8 weeks
• Must have normal organ and marrow function as defined below:
• leukocytes, greater than or equal to 3,000/μl
• absolute neutrophil count, greater than or equal to 1,500/μl
• platelets, greater than or equal to100,000/μl
• total bilirubin, less than or equal to 2.5 X institutional upper limit of normal
• AST(SGOT)/ALT(SGPT), less than or equal to 2.5 X institutional upper limit of normal (ULN)
• AST(SGOT)/ALT(SGPT), less than or equal to 5 X institutional ULN in patients with liver metastasis
• creatinine, less than or equal to 1.5 X institutional ULN

You may not qualify if:

• Prior chemotherapy for pancreatic adenocarcinoma in the metastatic setting are not eligible.
• Chemoradiation within the last 6 weeks prior to registration are not eligible
• Known allergy or severe reactions to gemcitabine, capecitabine, or tyrosine kinase inhibitors are not eligible
• May not be receiving any other investigational agents or received investigational agents within the 28 days prior to registration.
• Known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events.
• Prior malignancy in the last 3 years, except basal cell carcinoma, squamous cell, or in-situ cervical cancer
• ECOG PS 3-4
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because gemcitabine and capecitabine are Class D agents with the potential for teratogenic or abortifacient effects.
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, human immunodeficiency virus (HIV) positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with erlotinib or other agents administered during the study.
• Creatinine clearance \< 30 ml/min (Cockcroft-Gault method)
• Patients that require ongoing (chronic) treatment with medications metabolized by CYP3A4 (saquinavir, ritonavir, nelfinavir, indinavir, ketoconazole, itraconazole, nefazodone, clarithromycin, atazanavir, rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John's Wort) who cannot be switched to alternate medications that are not metabolized by CYP3A4 are excluded.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Capecitabine; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gregory Springett, M.D., Ph.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 29, 2007
• First Posted: May 31, 2007
• Study Start: April 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 8, 2012

Record last verified: 2012-11

Locations

US (1)