Study Of Advanced Gastrointestinal Malignancies And Other Solid Tumors

Phase I Study Of Oxaliplatin, Gemcitabine And Capecitabine In Advanced Gastrointestinal Malignancies And Other Solid Tumors

Dose escalation of oxaliplatin, gemcitabine and capecitabine in the treatment of patients with advanced gastrointestinal malignancies and other solid tumors.

Study Overview

• Status: Completed
• Conditions: Solid Tumors; Advanced Gastrointestinal Malignancies
• Intervention / Treatment: Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Capecitabine

Detailed Description

To define the maximum tolerated dose of oxaliplatin, gemcitabine and capecitabine in the treatment of patients with advanced gastrointestinal malignancies and other solid tumors.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histological Diagnosis: Patients must have a histological or cytological proven advanced gastrointestinal or other solid malignancy.
2. Measurable or Evaluable Disease: See RECIST Criteria: www.cancer.gov/dip/RECIST
3. Age: Patients must be 18 years old or older. Because no dosing or toxicity data are currently available on the use of oxaliplatin in patients <18 years of age, children are excluded from this study, but will be eligible for other pediatric Phase I single-agent trials, when available.
4. Performance Status: NCI CTC 0-2.
5. Life Expectancy: >=8 weeks.
6. Recovery from Prior Therapy: Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and must be without significant systemic illness (e.g. infection). No chemotherapy or radiotherapy may be given within 3 weeks prior to the start of protocol treatment. Patients must have received <= 2 prior chemotherapy regimes.
7. Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
8. Hematological Status: Patients must have adequate bone marrow function which is defined as an absolute neutrophil count >= 1,500/mm³, platelet count >= 100,000/mm³ and hemoglobin >= 9 g/dl.
9. Hepatic Function: Total bilirubin must be <= institutional limit of normal (ULN). Transaminases (SGOT and/or SGPT) must be <= 4 x ULN.
10. Neurological Status: Patients must not have active CNS metastases. Patients with Grade 2 or higher peripheral neuropathy are ineligible due to the potential neurological complications of oxaliplatin therapy.
11. Renal Function: Patients must have adequate renal function defined as serum creatinine <= 2.0 mg/dl or creatinine clearance >= 60 ml/min/1.73m² for patients with creatinine levels above 2.0 mg/dl.
12. Sexually Active Patients: For all sexually active patients, the use of adequate barrier contraception (hormonal or barrier method of birth control) will be required during therapy, prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential. Pregnant and nursing women patients are not eligible.
13. HIV-Positive Patients: Patients receiving anti-retroviral therapy (HAART) for HIV infection are excluded from the study because of possible pharmacokinetic interactions. Appropriate protocols will be offered to patients receiving HAART therapy, when indicated.
14. No known hypersensitivity to oxaliplatin, gemcitabine or capecitabine
15. No pre-existing clinically significant cardiac, hepatic or renal disease.
16. Informed Consent: After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
17. Inclusion of Women and Minorities: Entry to this study is open to both men and women and to all racial and ethnic groups.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1 (starting level); Oxaliplatin 85 mg/m2 IV on days 1 and 15. Gemcitabine 800 mg/m2 IV on days 1 and 15. Capecitabine 600 mg/m2 BID orally on days 1-7 and days 15-21 rounded off to the nearest 150 mg or 500 mg tablet. Each cycle is 28 days.	Drug: Gemcitabine; Other Names: Gemzar; Drug: Oxaliplatin; Drug: Capecitabine; Other Names: Xeloda
Experimental: Dose Level 2; Oxaliplatin 100 mg/m2 IV on days 1 and 15. Gemcitabine 800 mg/m2 IV on days 1 and 15. Capecitabine 600 mg/m2 BID orally on days 1-7 and days 15-21 rounded off to the nearest 150 mg or 500 mg tablet. Each cycle is 28 days.	Drug: Gemcitabine; Other Names: Gemzar; Drug: Oxaliplatin; Drug: Capecitabine; Other Names: Xeloda
Experimental: Dose Level 3; Oxaliplatin 100 mg/m2 IV on days 1 and 15. Gemcitabine 800 mg/m2 IV on days 1 and 15. Capecitabine 800 mg/m2 BID orally on days 1-7 and days 15-21 rounded off to the nearest 150 mg or 500 mg tablet. Each cycle is 28 days.	Drug: Gemcitabine; Other Names: Gemzar; Drug: Oxaliplatin; Drug: Capecitabine; Other Names: Xeloda
Experimental: Dose Level 4; Oxaliplatin 100 mg/m2 IV on days 1 and 15. Gemcitabine 1000 mg/m2 IV on days 1 and 15. Capecitabine 800 mg/m2 BID orally on days 1-7 and days 15-21 rounded off to the nearest 150 mg or 500 mg tablet. Each cycle is 28 days.	Drug: Gemcitabine; Other Names: Gemzar; Drug: Oxaliplatin; Drug: Capecitabine; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To define the maximum tolerated dose of oxaliplatin, gemcitabine and capecitabine in the treatment of patients with advanced gastrointestinal malignancies and other solid tumors.	At the end of dose escalation (approximately 18 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the dose-limiting toxicity of oxaliplatin, gemcitabine and capecitabine in the treatment of patients with advanced gastrointestinal malignancies and other solid tumors.	Completion of 1st cycle	Approximately 28 days into treatment
To evaluate the incidence and severity of other toxicities of oxaliplatin, gemcitabine and capecitabine in the treatment of patients with advanced gastrointestinal malignancies and other solid tumors.		30 days after the end of treatment
To perform a structured neurological assessment and questionnaire and report neurological toxicities of oxaliplatin when used with this combination.		30 days after end of treatment
To perform correlative pharmacogenomic and pharmacokinetic tests for this novel regimen.	PKs - expanded cohort only	Day 1, 7, 15, and 21

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: April 11, 2008
• First Submitted That Met QC Criteria: April 16, 2008
• First Posted (Estimate): April 17, 2008

Study Record Updates

• Last Update Posted (Estimate): April 23, 2013
• Last Update Submitted That Met QC Criteria: April 22, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: cancer; gastrointestinal; tumor
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Capecitabine; Oxaliplatin
• Other Study ID Numbers: 04-1213