Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma
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Purpose
| Condition | Intervention | Phase |
|---|---|---|
|
Advanced Malignant Mesothelioma Epithelioid Mesothelioma Recurrent Malignant Mesothelioma Sarcomatoid Mesothelioma |
Drug: Cediranib Maleate Drug: Cisplatin Drug: Pemetrexed Disodium Other: Placebo |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I/Randomized Phase II Study of Cediranib (NSC#732208) Versus Placebo in Combination With Cisplatin and Pemetrexed in Chemonaive Patients With Malignant Pleural Mesothelioma |
- Maximum tolerated dose determined if the dose-limiting toxicity rate is less than or equal to 33% according to NCI CTCAE version 4.0 (Phase I) [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
- Progression-free survival (Phase II) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]A stratified log-rank test at the 0.1 level will be used.
- Overall survival (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]A stratified log-rank test will be used to compare overall survival.
- Response (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]A stratified chi-square test will be used to compare response and toxicity between the two arms.
- Toxicity assessed using NCI CTCAE version 4.0 (Phase II) [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]A stratified chi-square test will be used to compare response and toxicity between the two arms.
| Estimated Enrollment: | 116 |
| Study Start Date: | March 2010 |
| Estimated Primary Completion Date: | December 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (phase II)
Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and oral cediranib maleate once daily at the maximum tolerated dose determined in phase I on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral cediranib maleate alone once daily in the absence of disease progression or unacceptable toxicity.
|
Drug: Cediranib Maleate
Given orally
Other Names:
Drug: Cisplatin
Given IV
Other Names:
Drug: Pemetrexed Disodium
Given IV
Other Names:
|
|
Active Comparator: Arm II (phase II)
Patients receive pemetrexed disodium and cisplatin as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral placebo alone once daily in the absence of disease progression or unacceptable toxicity.
|
Drug: Cisplatin
Given IV
Other Names:
Drug: Pemetrexed Disodium
Given IV
Other Names:
Other: Placebo
Given orally
Other Names:
|
Detailed Description:
OBJECTIVES:
I. To establish the maximum tolerated dose and the recommended phase II dose of cediranib maleate in combination with pemetrexed disodium and cisplatin in patients with malignant pleural mesothelioma. (Phase I) II. To compare the progression-free survival of patients treated with pemetrexed disodium and cisplatin with vs without cediranib maleate. (Phase II) III. To compare the overall survival of patients treated with these regimens. (Phase II) IV. To assess the safety and toxicity profile of these regimens. V. To assess the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (responsive or stable disease) using RECIST criteria and modified RECIST criteria for pleural tumors in a subset of patients with measurable disease. (Phase II) VI. To assess the rate of agreement between local and central pathology review of mesothelioma and its histologic subtypes. (Phase II) VII. To collect specimens for banking for use in future research studies. (Phase II)
OUTLINE: This is a multicenter, phase I dose-escalation study of cediranib maleate followed by a phase II randomized study. Patients enrolled in the phase II portion of the study are stratified according to Zubrod performance status (0-1 vs 2) and histologic subtype (epithelioid vs biphasic/sarcomatoid).
PHASE I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and oral cediranib maleate once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral cediranib maleate alone once daily in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and oral cediranib maleate once daily at the maximum tolerated dose determined in phase I on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral cediranib maleate alone once daily in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive pemetrexed disodium and cisplatin as in arm I and oral placebo once daily on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive oral placebo alone once daily in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up periodically for up to 3 years.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Histologically or cytologically confirmed malignant pleural mesothelioma
- Not planning to undergo surgical resection
- Patients must have measurable or non-measurable disease by both RECIST and modified RECIST criteria for pleural tumors as documented by CT scan; examinations for assessment of measurable disease must have been completed within 28 days prior to registration; examinations for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed and documented on the RECIST 1.1 and Modified RECIST Baseline Tumor Assessment Form
- Zubrod performance status 0-2
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL (transfusion allowed)
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGOT or SGPT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases are present)
- Serum creatinine ≤ 1.5 times ULN
- Creatinine clearance ≥ 60 mL/min
-
Proteinuria ≤ +1 on 2 consecutive dipsticks taken ≥ 7 days apart
- Repeat urinalysis not required provided first urinalysis shows no protein
- Not pregnant or nursing
- Fertile patients must agree to use effective contraception
- Must be able to swallow oral medications
- No mean QTc > 500 msec (with Bazett correction) by ECG or other significant ECG abnormality
- No NYHA class III-IV congestive heart failure
- No clinically significant hemoptysis, defined as > 1 tablespoon of bright red blood, within the past year
- No known HIV infection
- No other malignancy within the past 5 years except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I or II cancer from which the patient is currently in complete remission.
- No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer
-
No prior systemic therapy (chemotherapy or other biological therapy) for unresectable malignant pleural mesothelioma
- Prior systemicchemotherapy or biologic therapy as neoadjuvant or adjuvant therapy allowed provided disease has recurred and systemic therapy was completed > 6 months before study entry
- No prior therapy with any of the study drugs
- At least 28 days since prior surgery (e.g., pleurectomy, pleurodeses, thoracic or other major surgeries) and recovered
- At least 28 days since prior radiotherapy and recovered
- No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
- No concurrent drugs or biologics with proarrhythmic potential
- No concurrent major surgery
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01064648
Show 220 Study Locations
| Principal Investigator: | Anne Tsao | Southwest Oncology Group |
More Information
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT01064648 History of Changes |
| Other Study ID Numbers: | NCI-2011-02015 NCI-2011-02015 S0905 CDR0000665415 S0905 S0905 U10CA032102 |
| Study First Received: | February 5, 2010 |
| Last Updated: | September 14, 2016 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Mesothelioma Lung Neoplasms Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Mesothelial Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Lung Diseases Respiratory Tract Diseases Cediranib Cisplatin |
Pemetrexed Maleic acid Succinylcholine Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Protein Kinase Inhibitors Neuromuscular Depolarizing Agents Neuromuscular Blocking Agents Neuromuscular Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on September 30, 2016