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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by Asan Medical Center
Sponsor:
Collaborators:
Eli Lilly and Company
Korean Cancer Study Group
Information provided by (Responsible Party):
Sang-We Kim, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT01593293
First received: January 11, 2012
Last updated: May 5, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
Non-small Cell Lung Cancer
Drug: PemCarbo
Drug: Pem only
Phase 3

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 Randomized, Open-label, Phase III Study Comparing Pemetrexed With and Without Carboplatin in Elderly Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: The study lasts for 30 months of which subject accrual occurs in the first 24 months ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: Yes ]
    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)


Estimated Enrollment: 266
Study Start Date: March 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   70 Years and older
Genders Eligible for Study:   Both
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
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: NCT01593293

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

No publications provided

Responsible Party: Sang-We Kim, Professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT01593293     History of Changes
Other Study ID Numbers: AMC 2011-0857, AMC 2011-0857
Study First Received: January 11, 2012
Last Updated: May 5, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by 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
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on September 18, 2014