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
70 Years
N/A
Both
Non-small Cell Lung Cancer
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression free survival
Outcome Description:
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.
Outcome Time Frame:
The study lasts for 30 months of which subject accrual occurs in the first 24 months
Safety Issue:
Yes
Principal Investigator
Sang-We Kim, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Asan Medical Center
Authority:
Korea: Food and Drug Administration
Study ID:
AMC 2011-0857
NCT ID:
NCT01593293
Start Date:
March 2012
Completion Date:
November 2015
Related Keywords:
- Non-Small Cell Lung Cancer
- Elderly patients
- Non-squamous Non-small Cell Lung Cancer
- Pemetrexed
- Carboplatin
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
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