Eloxatin® Plus Gemcitabine Chemotherapy for Mesothelioma

• Overall Survival [ Time Frame: 50 months ] [ Designated as safety issue: Yes ]
• Progression-free Survival [ Time Frame: 50 months ] [ Designated as safety issue: Yes ]
  Time to radiologic disease progression or death

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

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.

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 IMTG TNM staging criteria (see Protocol Attachment 1). 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 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 (see Section 3.8.1.2).
  • 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 CT scans. At least one level must have one rind measurement ≥15 mm.
• CT (specifically spiral CT) scans and MRT 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 ECOG Performance Status Scale (after any palliative measures including pleural drainage have occurred). See Protocol Attachment 2.
• 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.