Eloxatin® Plus Gemcitabine Chemotherapy for Mesothelioma

• ClinicalTrials.gov Identifier: NCT00859469
• Recruitment Status: Completed
• First Posted: March 11, 2009
• Results First Posted: February 24, 2012
• Last Update Posted: October 30, 2019
• Sponsor: Columbia University
• Information provided by (Responsible Party): Columbia University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Mesothelioma	Drug: Oxaliplatin; Drug: Gemcitabine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Oxaliplatin (Eloxatin®) Plus Gemcitabine as First or Second-line Chemotherapy for Patients With Malignant Pleural or Peritoneal Mesothelioma: A Phase II Clinical Trial
• Study Start Date: April 2004
• Actual Primary Completion Date: March 2009
• Actual Study Completion Date: March 2013

Arms and Interventions

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 Name: Eloxatin; Drug: Gemcitabine; Gemcitabine 1000mg/m2 IV infusion for 90 minutes; Other Name: Gemzar

Outcome Measures

Primary Outcome Measures :

1. Best Response [ Time Frame: Two months ]
   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.

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: 50 months ]
2. Progression-free Survival [ Time Frame: 50 months ]
   Time to radiologic disease progression or death

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Investigators

• Principal Investigator: Robert N Taub, MD, PhD; Columbia University

More Information

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT00859469
• Other Study ID Numbers: AAAA2861
• First Posted: March 11, 2009
• Results First Posted: February 24, 2012
• Last Update Posted: October 30, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Columbia University:

Mesothelioma

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gemcitabine; Oxaliplatin; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs