Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma - Full Text View

Purpose

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.

Condition	Intervention	Phase
Advanced Malignant Mesothelioma Epithelioid Mesothelioma Recurrent Malignant Mesothelioma Sarcomatoid Mesothelioma	Drug: Pemetrexed Disodium Drug: Cisplatin Drug: Cediranib Maleate 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

Resource links provided by NLM:

MedlinePlus related topics: Mesothelioma

Drug Information available for: Cisplatin Pemetrexed Pemetrexed disodium

Genetic and Rare Diseases Information Center resources: Malignant Mesothelioma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

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.

Secondary Outcome Measures:

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: Pemetrexed Disodium Given IV Other Names: LY231514 MTA Drug: Cisplatin Given IV Drug: Cediranib Maleate Given orally Other Names: AZD2171 Recentin
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: Pemetrexed Disodium Given IV Other Names: LY231514 MTA Drug: Cisplatin Given IV Other: Placebo Given orally Other Name: PLCB

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: Pemetrexed Disodium

Given IV

Other Names:

LY231514
MTA

Drug: Cisplatin

Given IV

Drug: Cediranib Maleate

Given orally

Other Names:

AZD2171
Recentin

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: Pemetrexed Disodium

Given IV

Other Names:

LY231514
MTA

Drug: Cisplatin

Given IV

Other: Placebo

Given orally

Other Name: PLCB

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
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064648

Show 195 Study Locations

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Anne Tsao	Southwest Oncology Group

More Information

No publications provided


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01064648 History of Changes
Other Study ID Numbers:	NCI-2011-02015, NCI-2011-02015, CDR0000665415, S0905, S0905, U10CA032102
Study First Received:	February 5, 2010
Last Updated:	February 24, 2015
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Lung Neoplasms Mesothelioma Neoplasms, Mesothelial Adenoma Lung Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Cediranib	Cisplatin Pemetrexed Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Enzyme Inhibitors Folic Acid Antagonists Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protein Kinase Inhibitors Radiation-Sensitizing Agents Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015