Eloxatin® Plus Gemcitabine Chemotherapy for Mesothelioma

Oxaliplatin (Eloxatin®) Plus Gemcitabine as First or Second-line Chemotherapy for Patients With Malignant Pleural or Peritoneal Mesothelioma: A Phase II Clinical Trial

In patients with pleural or peritoneal mesothelioma, what is the response rate to combined Oxaliplatin (ELOXATIN®) and Gemcitabine chemotherapy?

Study Overview

• Status: Completed
• Conditions: Mesothelioma
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Gemcitabine

Detailed Description

Oxaliplatin (ELOXATIN®) is an organoplatinum complex which exerts its cytotoxic effect chiefly through inhibition of tumoral DNA synthesis and repair, leading to cellular apoptosis. The antiproliferative activity of oxaliplatin has been shown to approximate that of cisplatin or carboplatin in different tumor types.

This is a phase II clinical trial of Oxaliplatin (ELOXATIN®) plus gemcitabine as first or secondline chemotherapy for patients with malignant pleural or peritoneal mesothelioma. This study aims to determine the objective tumor response rate for Oxaliplatin plus gemcitabine given every 14 days in patients with malignant pleural mesothelioma and/or malignant peritoneal mesothelioma who have no more than one prior chemotherapy regimen. A total of 29 patients are expected to be enrolled in the study, each with a participation duration of 6 months.

Patients will be screened using standard health care assessments and tests. All of these tests must be done within 4 weeks before patients begin treatment. Patients who are deemed eligible will start the treatment cycle, defined as an interval of 14 days, and comprising of treatment with Gemcitabine followed immediately by Oxaliplatin. The study drugs will be administered in the following manner: Gemcitabine, at 1000 mg/m² IV infusion over 90 minutes, then Oxaliplatin, at 100 mg/m² IV infusion over 2 hours.

In the absence of specific indications for discontinuation of study drugs, patients will routinely be offered 6 cycles of therapy. Further cycles may be given if in the opinion of the investigator this is in the patient's best interest.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

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:

• Patients must have histologically confirmed malignant pleural or peritoneal mesothelioma epithelial, sarcomatoid, or mixed subtype, not amenable to curative treatment with surgery. Patients with pleural mesothelioma will be clinically staged using the International Mesothelioma Interest Group staging criteria. Note that there is no staging system for peritoneal mesothelioma and those patients will only be followed for survival. Patients may be entered based on local pathology.

• Disease status must be that of measurable disease as defined by modified Southwest Oncology Group (SWOG) criteria.

  • Measurable disease: The presence of at least one measurable lesion. If only one lesion is present, the neoplastic nature of the disease site should be confirmed by histology.
  • Measurable lesions: Lesions that can be accurately measured in at least one dimension with the longest diameter ≥20 mm using conventional techniques or ≥10 mm using spiral computerized tomography (CT) scans. At least one level must have one rind measurement ≥15 mm.
• CT (specifically spiral CT) scans and magnetic resonance imaging (MRI) are the preferred methods of measurement.
• Clinically detected lesions will only be considered measurable when they are superficial (e.g., skin nodules and palpable lymph nodes).
• For the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion is required.

NOTE: Neither pleural effusions nor positive bone scans are considered measurable.

• Patients may have undergone pleurodesis. If pleurodesis was performed, there must be at least a 2-week delay before Oxaliplatin or gemcitabine is administered. If the original CT scan occurred prior to the pleurodesis, an additional CT scan is required 2 weeks or longer after the pleurodesis, which will then be considered the baseline scan.

NOTE: For patients with clinically significant pleural effusions or ascites, consideration should be given to draining the fluid.

• Performance status of 0, 1 or 2 on Eastern Cooperative Oncology Group (ECOG) Performance Status Scale (after any palliative measures including pleural drainage have occurred).
• Estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

• More than one previous regimen of systemic chemotherapy. Prior intracavitary cytotoxic drugs will count as a prior regimen, unless given for the purpose of pleurodesis. Immunomodulators will not be regarded as chemotherapy. Prior systemic treatment with pemetrexed plus a platinum compound will not be a contraindication for gemcitabine-oxaliplatin.
• Prior radiation therapy to the target lesion, unless the lesion is clearly progressing and the interval between the most recent radiation therapy and enrollment is at least 4 weeks.
• Active infection (at the discretion of the investigator).
• Pregnancy or breast feeding.
• Serious concomitant systemic disorders (including oncologic emergencies) incompatible with the study (at the discretion of the investigator).
• Patients with a "currently active" second malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix are not to be registered. Patients who are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
• Use of any investigational agent within 4 weeks before enrollment into the study.
• Disease which cannot be radiologically imaged.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oxaliplatin and Gemcitabine; Gemcitabine 1000 mg/m² IV infusion over 90 minutes, then Oxaliplatin 100 mg/m² IV infusion over 2 hours repeated for 14 days up to 6 cycles	Drug: Oxaliplatin; Oxaliplatin 100 mg/m2 IV infusion for 2 hours; Other Names: Eloxatin; Drug: Gemcitabine; Gemcitabine 1000mg/m2 IV infusion for 90 minutes; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response	Radiologic response by RECIST criteria will be compared between baseline and at 2 months. Disease assessment: Two objective status determinations of CR before progression are required for a best response of CR. Two determinations of PR or better before progression, but not qualifying for a CR, are required for a best response of PR. Two determinations of stable/no response or better before progression, but not qualifying as CR or PR are required for a best response of stable/no response.	Two months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		50 months
Progression-free Survival	Time to radiologic disease progression or death	50 months

Collaborators and Investigators

• Sponsor: Columbia University

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): March 1, 2013

Study Registration Dates

• First Submitted: March 9, 2009
• First Submitted That Met QC Criteria: March 10, 2009
• First Posted (ESTIMATE): March 11, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 30, 2019
• Last Update Submitted That Met QC Criteria: October 15, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Mesothelioma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; 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; Oxaliplatin
• Other Study ID Numbers: AAAA2861

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED