A Study of Induction and Maintenance Treatment of Advanced Non-squamous Non-Small Cell Lung Cancer

NCT ID: NCT00789373

Last Updated: 2018-12-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

939 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2017-11-30

Brief Summary

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This study will compare progression-free survival in patients with advanced non-squamous non-small cell lung cancer. Patients who do not progress following 4 cycles of induction treatment with pemetrexed and cisplatin will be randomized 2:1 to receive either maintenance pemetrexed or placebo.

Detailed Description

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Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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pemetrexed + cisplatin followed by pemetrexed

pemetrexed plus cisplatin followed by pemetrexed plus best supportive care

Group Type EXPERIMENTAL

Pemetrexed

Intervention Type DRUG

Induction therapy: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles

Cisplatin

Intervention Type DRUG

Induction therapy: Cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles

Pemetrexed

Intervention Type DRUG

Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.

Best Supportive Care

Intervention Type OTHER

Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral).

pemetrexed + cisplatin followed by placebo

pemetrexed plus cisplatin followed by placebo plus best supportive care

Group Type PLACEBO_COMPARATOR

Pemetrexed

Intervention Type DRUG

Induction therapy: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles

Cisplatin

Intervention Type DRUG

Induction therapy: Cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles

Placebo

Intervention Type DRUG

Maintenance therapy: Normal saline (0.9% sodium chloride) administered IV on Day 1 every 21-day cycle until progressive disease or treatment discontinuation

Best Supportive Care

Intervention Type OTHER

Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral).

Interventions

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Pemetrexed

Induction therapy: 500 mg/m\^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles

Intervention Type DRUG

Cisplatin

Induction therapy: Cisplatin: 75 mg/m\^2, IV, on Day 1 of each 21-day cycle for 4 cycles

Intervention Type DRUG

Placebo

Maintenance therapy: Normal saline (0.9% sodium chloride) administered IV on Day 1 every 21-day cycle until progressive disease or treatment discontinuation

Intervention Type DRUG

Pemetrexed

Maintenance therapy: 500 mg/m\^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.

Intervention Type DRUG

Best Supportive Care

Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral).

Intervention Type OTHER

Other Intervention Names

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Alimta LY231514 Alimta LY231514

Eligibility Criteria

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Inclusion Criteria

* You must sign an informed consent document for clinical research.
* You must have Stage IIIB or IV nonsquamous Non-Small Cell Lung Cancer.
* You must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work.
* You are allowed to have had prior radiation therapy as long as it was not to more than 25% of the bone marrow and did not include the whole pelvis. Thoracic radiation must be completed more than 30 days before the study. You must be recovered from the toxic effects (except hair loss).
* You must have at least 1 measurable tumor lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated by computed tomography (CT) Scan.
* Your test results assessing the function of your blood forming tissue, kidneys, and liver must be satisfactory.
* You must be 18 years of age or older.
* Women must be sterile, postmenopausal or on contraception and men must be on contraception or sterile (e.g. post-vasectomy).


* You must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work.
* You must have documented radiographic evidence of a tumor response of complete response (CR), partial response (PR), or stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Tumor assessment must occur between Cycle 4 (Day 1) of induction therapy and the date of randomization. This response does not have to be confirmed in order for the patient to be randomized to the maintenance phase.

Exclusion Criteria

* You cannot have squamous cell and/or mixed small cell, non-small cell lung cancer
* You cannot have received other investigational drugs within the last 30 days of entering the trial.
* You cannot have previously completed or withdrawn from this study or any other study investigating pemetrexed.
* You cannot have other serious on-going illnesses including active infections.
* You cannot have a serious cardiac condition, such as a heart attack, angina, or heart disease within 6 months of entering the trial.
* You cannot have had another form of cancer other than superficial basal cell and superficial squamous (skin) cell cancer, or carcinoma in situ of the cervix within the last 5 years. Patients with a history of low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years ago.
* You cannot have known central nervous system (CNS) metastases, other than treated, stable brain metastasis.
* You cannot be receiving nor have received any prior systemic anticancer therapy for lung cancer (including chemotherapy given after surgery in early-stage treatment).
* You cannot have clinically significant third-space fluid collections (e.g. ascites or pleural effusions that cannot be controlled by drainage or other procedures).
* You cannot have received a recent (within 30 days) or are receiving a yellow fever vaccination.
* You are unable to stop taking more than 1.3 grams of aspirin on a daily basis or other non-steroidal anti-inflammatory drugs (NSAIDs).
* You are unable or unwilling to take folic acid, injections of vitamin B12, or corticosteroids.
* You cannot be pregnant or breastfeeding.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Adelaide, South Australia, Australia

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Frankston, Victoria, Australia

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Wendouree, Victoria, Australia

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Aalst, , Belgium

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Brussels, , Belgium

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Genk, , Belgium

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Gilly, , Belgium

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Liège, , Belgium

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Sint-Niklaas, , Belgium

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Espoo, , Finland

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Helsinki, , Finland

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Tampere, , Finland

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Turku, , Finland

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Avignon, , France

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Dijon, , France

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Le Mans, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Vandœuvre-lès-Nancy, , France

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Frankfurt, , Germany

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Gerlingen, , Germany

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Großhansdorf, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Ulm, , Germany

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Athens, , Greece

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Chania, , Greece

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Neo Faliro, , Greece

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Pátrai, , Greece

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Bangalore, , India

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Bhopal, , India

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Madurai, , India

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Mumbai, , India

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Patna, , India

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Avellino, , Italy

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Aviano, , Italy

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Genova, , Italy

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Lido di Camaiore, , Italy

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Monza, , Italy

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Pisa, , Italy

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Reggio Emilia, , Italy

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Rome, , Italy

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Udine, , Italy

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Ede, , Netherlands

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Groningen, , Netherlands

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Harderwijk, , Netherlands

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Heerlen, , Netherlands

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Poznan, , Poland

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Warsaw, , Poland

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Coimbra, , Portugal

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Lisbon, , Portugal

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Vila Franca de Xira, , Portugal

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Oradea, , Romania

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Manresa, , Spain

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Sabadell, , Spain

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Seville, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Bornova, , Turkey (Türkiye)

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Sihhiye, , Turkey (Türkiye)

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Zeytinburnu, , Turkey (Türkiye)

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Aberdeen, Scotland, United Kingdom

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Guildford, Surrey, United Kingdom

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Birmingham, West Midlands, United Kingdom

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Newcastle, , United Kingdom

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Countries

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Canada Australia Belgium Finland France Germany Greece India Italy Netherlands Poland Portugal Romania Spain Turkey (Türkiye) United Kingdom

References

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Middleton G, Gridelli C, De Marinis F, Pujol JL, Reck M, Ramlau R, Parente B, Pieters T, Visseren-Grul CM, San Antonio B, John WJ, Zimmermann AH, Chouaki N, Paz-Ares L. Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. Curr Med Res Opin. 2018 May;34(5):865-871. doi: 10.1080/03007995.2018.1439462. Epub 2018 Mar 27.

Reference Type DERIVED
PMID: 29424248 (View on PubMed)

Pujol JL, Paz-Ares L, de Marinis F, Dediu M, Thomas M, Bidoli P, Corral J, San Antonio B, Chouaki N, John W, Zimmermann A, Visseren-Grul C, Gridelli C. Long-term and low-grade safety results of a phase III study (PARAMOUNT): maintenance pemetrexed plus best supportive care versus placebo plus best supportive care immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. Clin Lung Cancer. 2014 Nov;15(6):418-25. doi: 10.1016/j.cllc.2014.06.007. Epub 2014 Jun 21.

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PMID: 25104617 (View on PubMed)

Reck M, Paz-Ares LG, de Marinis F, Molinier O, Sahoo TP, Laack E, John W, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Descriptive subgroup analyses of final overall survival for the phase III study of maintenance pemetrexed versus placebo following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2014 Feb;9(2):205-13. doi: 10.1097/JTO.0000000000000076.

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Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. doi: 10.1200/JCO.2012.47.1102. Epub 2013 Jul 8.

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Zeng X, Peng L, Li J, Chen G, Tan C, Wang S, Wan X, Ouyang L, Zhao Z. Cost-effectiveness of continuation maintenance pemetrexed after cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the Chinese health care system. Clin Ther. 2013 Jan;35(1):54-65. doi: 10.1016/j.clinthera.2012.12.013.

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PMID: 23328269 (View on PubMed)

Gridelli C, de Marinis F, Pujol JL, Reck M, Ramlau R, Parente B, Pieters T, Middleton G, Corral J, Winfree K, Melemed S, Zimmermann A, John W, Beyrer J, Chouaki N, Visseren-Grul C, Paz-Ares LG. Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2012 Nov;7(11):1713-21. doi: 10.1097/JTO.0b013e318267cf84.

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PMID: 23059776 (View on PubMed)

Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. doi: 10.1016/S1470-2045(12)70063-3. Epub 2012 Feb 16.

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PMID: 22341744 (View on PubMed)

Paz-Ares LG, Altug S, Vaury AT, Jaime JC, Russo F, Visseren-Grul C. Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer. BMC Cancer. 2010 Mar 8;10:85. doi: 10.1186/1471-2407-10-85.

Reference Type DERIVED
PMID: 20211022 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

H3E-EW-S124

Identifier Type: OTHER

Identifier Source: secondary_id

CTRI/2009/091/000113

Identifier Type: REGISTRY

Identifier Source: secondary_id

12560

Identifier Type: -

Identifier Source: org_study_id