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A Phase I Trial of GemCap-T, Capecitabine in Combination With Gemcitabine and Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Adenocarcinoma

Phase 1
18 Years
Not Enrolling
Metastatic Pancreatic Carcinoma

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Trial Information

A Phase I Trial of GemCap-T, Capecitabine in Combination With Gemcitabine and Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Adenocarcinoma

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. This combination of
drugs has never been used before.

Screening tests will consists of demographics, a medical history, and physical exam, vital
signs, height, weight, performance status, blood counts, chemistries, and clotting. There
will also be an electrocardiogram (EKG), tumor measurement (computed tomography [CT Scan] or
magnetic resonance imaging [MRI] or positron emission tomography CT [PET-CT]), cancer
antigen (CA 19-9), and a serum pregnancy test (for women of childbearing potential). Tumor
measurements are also performed after cycle 2, 4, and 6 (study end).

Treatment will be administered on an outpatient basis and consists of both intravenous (IV)
medication and tablets taken by mouth. The gemcitabine will be administered at Moffitt once
per week for 3 weeks, followed by a week off treatment. One tablet of erlotinib will be
taken by mouth continuously starting with day one of cycle 1 while capecitabine will be
taken twice per day on days 1-14 of each cycle followed by a 2 week off treatment rest
period. This set of treatments is called a cycle. One full cycle of treatment will last 28
days and a total of 6 cycles of treatments are planned. Before each cycle we will repeat the
blood counts and a brief physical exam (vital signs) will be recorded weekly during the
first 3 weeks of the 28 day cycle of treatment (when receiving Gemcitabine).

An accelerated dose-escalation scheme will be employed with 4 planned dose levels. Patients
will be enrolled at the lowest dosage level, if no patients have unacceptable toxicity, the
dose will be escalated and additional patients enrolled. If one of the patients at a given
dose level experiences a dose limiting toxicity (DLT), more patients will be treated at that
dose level. When 2 patients have DLTs at the same dose, the dose will be deescalated to the
previous dose and additional patients will be enrolled. After de-escalation begins, 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. Patients may continue on the study regimen unless they
experience an adverse event that meets the criteria for a dose limiting toxicity.

Inclusion Criteria:

- Histologically confirmed pancreatic adenocarcinoma that is metastatic or

- 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

- 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:

1. leukocytes, greater than or equal to 3,000/μl

2. absolute neutrophil count, greater than or equal to 1,500/μl

3. platelets, greater than or equal to100,000/μl

4. total bilirubin, less than or equal to 2.5 X institutional upper limit of normal

5. AST(SGOT)/ALT(SGPT), less than or equal to 2.5 X institutional upper limit of
normal (ULN)

6. AST(SGOT)/ALT(SGPT), less than or equal to 5 X institutional ULN in patients
with liver metastasis

7. creatinine, less than or equal to 1.5 X institutional ULN

8. creatinine clearance, > 30 ml/min (Cockcroft-Gault method)

- Has a negative serum or urine pregnancy test within 7 days prior to initiation of
therapy (female patients of childbearing potential).

- Postmenopausal women must have been amenorrheic for at least 12 months to be
considered of non-childbearing potential. Patients will agree to continue
contraception for 30 days from the date of the last study drug administration.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Prior chemotherapy for pancreatic adenocarcinoma in the metastatic setting are not

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

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.

Outcome Time Frame:

Within 4 months of Cycle 1 Day 1 (C1D1)

Safety Issue:


Principal Investigator

Gregory Springett, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

April 2007

Completion Date:

November 2012

Related Keywords:

  • Metastatic Pancreatic Carcinoma
  • pancreatic
  • gemcitabine
  • erlotinib (HER1/epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor)
  • capecitabine
  • Carcinoma
  • Pancreatic Neoplasms



H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612