Capecitabine, Docetaxel and Gemcitabine in Patients With Advanced Pancreas Cancer

A Dose Escalating (Phase I) Study Looking at the Biomodulation of Capecitabine by Docetaxel and Gemcitabine in Patients With Advanced Pancreas Cancer

The primary purpose of this study is to define the maximum tolerated dose of combination docetaxel, gemcitabine, and capecitabine in patients with pancreatic cancer. Adverse effects will be measured in study participants. In addition, researchers will assess data about preliminary efficacy in patients with this treatment approach.

Rationale: Single agent gemcitabine is considered standard care for patients with advanced pancreatic cancer. However, better treatments offering improved outcomes are needed for people with this disease. The combination of docetaxel and capecitabine has shown significant and broad clinical activity in a variety of tumors. Laboratory research on the combination of capecitabine, docetaxel, and gemcitabine indicates synergistic action against tumor cells. The current study will test this combination in patients. The drug administration schedule in this study is aimed at maximizing the potential of activation of capecitabine by both docetaxel and gemcitabine. Treatment: Study participants will be given docetaxel, gemcitabine, and capecitabine. All study drugs will be administered through intravenous infusions in three week cycles. Docetaxel will be given on days 1 and 8, gemcitabine on days 8 and 15, and capecitabine on days 8 through 21. This schedule will be followed by 1 week of rest without administration of study drugs. Since the primary goal of this study is to identify the maximum tolerated dose of the study drugs in combination, patients who enroll in the beginning of the study will receive lower amounts of the study drugs compared to patients who enroll later in the study. Several tests and exams will be given throughout the study to closely monitor patients.

Dose escalation study of mGTX using three dose levels (DL1-3). Patients received docetaxel on days 1 and 8, gemcitabine on days 8 and 15, and capcitabine on days 8 through 21. Gemcitabine fixed dose at 750 mg/m2 over 75 min, capecitabine twice daily and escalated from 500 to 650 mg/m2 at DL2 and docetaxel increased from 30 to 36 mg/m2 at DL3.

MTD will be the dose at which 1 or fewer patients (≤ 1/6) experiences a DLT during the first or second cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing Dose Limiting Toxicities (DLT).

The NCI Common Terminology Criteria for Adverse Events version 3.0 was used for adverse event reporting and toxicity grading.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Inclusion Criteria: adenocarcinoma of the pancreas no prior chemo except adjuvant Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 peripheral neuropathy </= Gr. 1 Exclusion Criteria: Pregnant/lactating females Uncontrolled heart disease, diabetes, psychiatric disorder Therapeutic doses of Warfarin

Hill ME, Li X, Kim S, Campbell A, Culler K, Bloomston M, Zalupski M, Hejna G, Bekaii-Saab T. A phase I study of the biomodulation of capecitabine by docetaxel and gemcitabine (mGTX) in previously untreated patients with metastatic adenocarcinoma of the pancreas. Cancer Chemother Pharmacol. 2011 Mar;67(3):511-7. doi: 10.1007/s00280-010-1348-3. Epub 2010 May 12.