Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01064648
First received: February 5, 2010
Last updated: October 17, 2014
Last verified: June 2014

February 5, 2010
October 17, 2014
March 2010
December 2016   (final data collection date for primary outcome measure)
  • 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.
  • Maximum tolerated dose of cediranib maleate (Phase I) [ Designated as safety issue: Yes ]
  • Progression-free survival (Phase II) [ Designated as safety issue: No ]
  • Safety and toxicity (Phase I) [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01064648 on ClinicalTrials.gov Archive Site
  • 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.
  • Overall survival (Phase II) [ Designated as safety issue: No ]
  • Response rate (confirmed and unconfirmed, complete and partial responses) (Phase II) [ Designated as safety issue: No ]
  • Disease control rate (responsive or stable disease) (Phase II) [ Designated as safety issue: No ]
  • Safety and toxicity profile (Phase II) [ Designated as safety issue: Yes ]
  • Rate of agreement between local and central pathology review of mesothelioma and its histologic subtypes (Phase II) [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma
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

This randomized phase I/II trial is studying the side effects and best dose of cediranib maleate when given together with pemetrexed disodium and cisplatin and to see how well it works in treating patients with malignant pleural mesothelioma. Drugs used in chemotherapy, pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving pemetrexed disodium and cisplatin together with cediranib maleate may kill more tumor cells.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Advanced Malignant Mesothelioma
  • Epithelial Mesothelioma
  • Recurrent Malignant Mesothelioma
  • Sarcomatous Mesothelioma
  • Drug: pemetrexed disodium
    Given IV
    Other Names:
    • ALIMTA
    • LY231514
    • MTA
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: cediranib maleate
    Given orally
    Other Names:
    • AZD2171
    • Recentin
  • Other: placebo
    Given orally
    Other Name: PLCB
  • 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.
    Interventions:
    • Drug: pemetrexed disodium
    • Drug: cisplatin
    • Drug: cediranib maleate
  • 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.
    Interventions:
    • Drug: pemetrexed disodium
    • Drug: cisplatin
    • Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
116
Not Provided
December 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT01064648
NCI-2011-02015, NCI-2011-02015, CDR0000665415, S0905, S0905, U10CA032102
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Anne Tsao Southwest Oncology Group
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP