Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation Therapy for Mesothelioma

Phase II Study of Neo-adjuvant Pemetrexed (ALIMTA) Plus Cisplatin Followed by Surgery and Radiation Therapy for Malignant Pleural Mesothelioma

Despite the best surgical efforts, complete removal of mesothelioma is possible in approximately 30% of the patients. When surgical removal is complete, chemotherapy followed by radiation therapy is recommended as an effort to improve control over the cancer and survival. This combination of treatments is called TRIMODALITY therapy. Unfortunately, the chances for the tumor coming back after TRIMODALITY therapy remains high. When surgical removal is not complete or not possible, some patients may receive chemo and/or radiation therapy to achieve control over the cancer, but the chances of tumor to growth again remains high and the chances of long term survival remains low.

The combination of Pemetrexed (Alimta) with Cisplatin has been approved as one of the standard chemotherapy drug combinations for the treatment in advanced Malignant Pleural Mesothelioma, and there is likely a group of patients who may benefit and potentially be cured by this therapy. In an effort to achieve a better chance of complete removal of the cancer and long term survival, the investigators are interested in using this drug combination of Pemetrexed + Cisplatin before surgery and offer radiation therapy after surgery.

Study Overview

• Status: Terminated
• Conditions: Mesothelioma; Pleural Mesothelioma
• Intervention / Treatment: Drug: Pemetrexed; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network

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. Histologically proven diagnosis of MPM stages I to III. Patients will be clinically staged using the AJCC/UICC TNM staging criteria (see Protocol Appendix 2). Eligible stages:

   • Patients must be M0.
   • Patients with T1, T2, and T3 disease (without cardiac involvement) are eligible. T status can be established clinically and radiologically or at exploratory thoracotomy without surgical resection.
   • Patients with N0, N1, or N2 disease are eligible.
2. Performance status of 0 to 2 on the ECOG performance status schedule. See protocol Appendix 3
3. No prior systemic chemotherapy. No prior intracavitary cytotoxic drugs or immunomodulators, unless given for the purpose of chemical pleurodesis.
4. No previous surgical procedure for mesothelioma, with the exception of previous chemical pleurodesis and biopsy.
5. No previous radiation therapy for mesothelioma, or to the thorax.
6. Patients must be judged to be suitable candidates for this therapy at the UHN by the attending medical oncologist, thoracic surgeon, and radiation oncologist before enrolment.
7. Estimated life expectancy of at least 12 weeks.

8. Adequate organ function including the following:

   • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ³1,500/uL , platelets ³100,000/uL, hemoglobin ³ 9g/dL
   • Hepatic: bilirubin £1.5 times institutional upper limit of normal, alkaline phosphatase (AP), aspartate transaminase (AST) and alanine transaminase (ALT) £3 times institutional upper limit of normal
   • Renal: Creatinine £1.5 times institutional upper limit of normal; or Creatinine clearance ³50 mL/min/1.73 m² for patients with creatinine levels above institutional normal upper limit level. Cockcrot and Gault formula Appendix 4.
   • Pulmonary function tests:

   Predicted post-operative DLCO (ppoDLCO) of > 35%.

   If the ppoDLCO is </= 35%, then additional studies will be done to determine the patient's ability to tolerate the resection. The surgeon will correlate these results with the patient's clinical status and make a decision as to the feasibility of resection.

9. Female patients of childbearing potential must test negative for pregnancy at the time of enrolment based on a serum pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 3 months following the last dose of radiation therapy.
10. Patients must sign an informed consent

Exclusion Criteria:

1. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
2. Have previously completed or withdrawn from this study or any other study investigating pemetrexed
3. Pregnancy or breast-feeding.
4. Serious concomitant systemic disorders (e.g., active infection) that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
5. Second active primary malignancy except in situ carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin, low grade (Gleason score < 6) localized adenocarcinoma of the prostate or other malignancy treated at least 2 years previously with no evidence of recurrence.
6. Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8 day period for long-acting agents such as piroxicam).
7. Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone.
8. Refusal to have any of the treatment in the protocol (chemotherapy, extrapleural pneumonectomy, and radiation therapy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alimta plus Cisplatin	Drug: Pemetrexed; 500 mg/m² iv infusion every 3 weeks for 3 cycles; Other Names: Alimta; Drug: Cisplatin; 75 mg/m² iv infusion every 3 weeks for 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
median relapse-free survival (RFS)	15 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Ron Feld, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: May 6, 2009
• First Submitted That Met QC Criteria: May 7, 2009
• First Posted (Estimate): May 8, 2009

Study Record Updates

• Last Update Posted (Actual): May 4, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: mesothelioma; pleura; pleural; Meso
• 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; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 05-0815-C