Pemetrexed With or Without Carboplatin for Elderly Non-squamous Non-small Cell Lung Cancer (ACE)

• ClinicalTrials.gov Identifier: NCT01593293
• Recruitment Status: Unknown
• First Posted: May 8, 2012
• Last Update Posted: May 8, 2012
• Sponsor: Asan Medical Center
• Collaborators: Eli Lilly and Company; Korean Cancer Study Group
• Information provided by (Responsible Party): Sang-We Kim, Asan Medical Center

Study Description

Brief Summary:

The number of NSCLC patients above 70 years of age who are non-squamous histology is increasing around the world. Although previous guidelines often recommend single agent therapy for NSCLC, recent studies suggest that platinum doublets may be better than standard monotherapy in elderly. We hypothesize that for elder patients (≥70 years of age) with non-squamous NSCLC, pemetrexed and carboplatin is more effective than pemetrexed monotherapy in terms disease progression, overall survival, and quality of life and tolerability.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: PemCarbo; Drug: Pem only	Phase 3

Detailed Description:

The treatment of NSCLC in elderly has been subject to discussion for years. While platinum doublets consisting of cisplatin or carboplatin and another cytotoxic agent demonstrate a survival advantage compared with single agents generally, evidence of treatment efficacy for patients with diminished performance status (PS) or with age older than 70 years is limited. Guidelines from the US and Europe have preferred single-agent chemotherapy for the elderly and PS 2 patients. However, increasing studies are exploring this issue and presenting data that favour doublet therapy. The addition of carboplatin to paclitaxel and cisplatin to docetaxel have shown evidence that patients over 70 benefit more in face of increased toxicities.

This study is designed to be multi-center, open-label, prospective, randomized, two-arm, parallel, phase III trial of elderly patients(≥70 years old) with metastatic non-squamous NSCLC (Stage IV by AJCC 7th) who have not received prior systemic chemotherapy or biological therapy. Approximately 266 patients will be enrolled into the trial. This study compares the doublet therapy of pemetrexed (500 mg/m2) and carboplatin (AUC 5 mg/mL*min) administered intravenously every 21 days for 4 cycles followed by pemetrexed (500 mg/m2) every 21 days for maintenance therapy (Arm A) to single therapy of pemetrexed (500 mg/m2) every 21 days till progression or unacceptable toxicity (Arm B). Pemetrexed will be administered with vitamin B12 and folate supplements.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 266 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-label, Phase III Study Comparing Pemetrexed With and Without Carboplatin in Elderly Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer
• Study Start Date: March 2012
• Estimated Primary Completion Date: November 2014
• Estimated Study Completion Date: November 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: PemCarbo; Pemetrexed/Carboplatin arm	Drug: PemCarbo; Pemetrexed 500mg/m2, Carboplatin AUC5 intravenously q 3 weeks for 4 cycles, followed by pemtrexed 500mg/m2 q 3 weeks for maintenance therapy; Other Name: Alimta: brand name of Pemetrexed
Active Comparator: Pem only; Pemetrexed arm	Drug: Pem only; Pemetrexed 500mg/m2 intrvenously q 3 weeks till progression or unacceptable toxicity.; Other Name: Alimta: brand name of pemetrexed

Outcome Measures

Primary Outcome Measures :

1. Progression free survival [ Time Frame: The study lasts for 30 months of which subject accrual occurs in the first 24 months ]
   To compare the progression free survival of elderly patients (≥70 years old) with non-squamous NSCLC receiving doublet of carboplatin and pemetrexed to patients receiving pemetrexed alone.

Secondary Outcome Measures :

1. Objective response rate, Overall survival, Safety and Quality of life [ Time Frame: The study lasts for 30 months of which subject accrual occurs in the first 24 months ]

   1. To compare the following efficacy variables between treatment arms:

      • Objective response rate
      • Overall survival
   2. To compare the safety and adverse event profile between treatment arms
   3. To assess the impact of treatment on patient-rated quality of life (FACT-L)

Eligibility Criteria

• Ages Eligible for Study: 70 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically confirmed advanced non-squamous non-small cell lung cancer (stage IV, AJCC 7th)
• Age 70 years old or older
• Eastern Cooperative Oncology Group performance status 0-1
• Measurable or assessable disease as defined by RECIST 1.1
• Estimated life expectancy of more than 3 months
• Adequate bone marrow function(Absolute Neutrophil Count (ANC) ≥ 1,500/µL, platelets ≥ 100,000/µL, hemoglobulin ≥ 9 g/dL)
• Adequate renal function: creatinine < 1 x upper normal limit (UNL) or creatinine clearance(Ccr) using Cockroft and Gault formula ≥45 ml/min
• Adequate hepatic function: bilirubin < 1.5 x UNL, AST/ALT levels < 3 x UNL, alkaline phosphatase < 3 x UNL (except in case of bone metastasis without any liver disease)
• Written informed consent

Exclusion Criteria:

• Prior systemic chemotherapy or biological therapy
• Contraindication to any drug contained in the chemotherapy regimen
• Clinically significant third-space fluid collections (e.g. pleural effusion and pericardial effusion) that cannot be controlled by drainage or other procedures prior to study enrollment
• Active infection which would compromise the patient's ability to tolerate treatment
• Requirement for major surgery within 4 weeks of study entry
• Myocardial infarction, uncontrolled arrhythmias, symptomatic angina pectoris, cardiac failure within the previous 6 months
• Unable to discontinue administration of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs); Aspirin or NSAIDs should be at least 5 days before pemetrexed administration
• Presence or history of CNS metastasis (except if adequately treated and is not receiving steroid therapy for at least 2 weeks; at least 2 weeks for whole brain radiation or at least 1 week for gamma knife surgery)
• Peripheral neuropathy ≥ grade 2
• History of another malignancy within the last five years except cured basal cell carcinoma of skin, cured carcinoma in-situ of uterine cervix and cured thyroid malignancy
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions

Contacts and Locations

Contacts

Contact: Sang-We Kim, M.D.; 82-2-3010-3215; swkim@amc.seoul.kr

Locations

Korea, Republic of

Asan Medical Center; Recruiting

Seoul, Korea, Republic of, 138-736

Contact: Sang-We Kim, M.D. 82-2-3010-3215 swkim@amc.seoul.kr

Sponsors and Collaborators

Asan Medical Center

Eli Lilly and Company

Korean Cancer Study Group

Investigators

• Principal Investigator: Sang-We Kim, M.D.; Asan Medical Center

More Information

• Responsible Party: Sang-We Kim, Professor, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT01593293
• Other Study ID Numbers: AMC 2011-0857; AMC 2011-0857 ( Other Identifier: Asan Medical Center )
• First Posted: May 8, 2012
• Last Update Posted: May 8, 2012
• Last Verified: May 2012

Keywords provided by Sang-We Kim, Asan Medical Center:

Elderly patients; Non-squamous Non-small Cell Lung Cancer; Pemetrexed; Carboplatin

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors