Alimta and Gemcitabine in Non-Small Cell Lung Cancer (ANGEL)

A Phase II Randomized Trial Assessing the Combination of Gemcitabine and Pemetrexed in the First Line Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer

The aims of this study are: (1) to assess the safety and activity of gemcitabine plus Alimta (pemetrexed) regimen (GA regimen) in patients with advanced NSCLC patients in the context of a randomized trial, and (2) to compare the GA with the paclitaxel plus gemcitabine (PG regimen) in terms of toxicity and QoL

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer; Stage IIIB or IV
• Intervention / Treatment: Drug: gemcitabine plus pemetrexed, paclitaxel plus gemcitabine

Detailed Description

Patients with stage IIIB or IV non-small cell lung cancer will be randomly allocated to receive: (a)PG regimen: paclitaxel 120 mg/sqm followed by gemcitabine 1,000 mg/sqm i.v. on days 1 & 8 q 3 weeks; (b)GA regimen: gemcitabine 1,250 mg/sqm i.v. on day 1 (plus folinic acid 350 μg daily orally and vitamin B12 1,000 μg i.m. q 9 weeks), pemetrexed (Alimta®) 500 mg/sqm i.v. on day 8 followed by gemcitabine 1,250 mg/sqm, q 3 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • National Tumor Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) NSCLC
2. No previous adjuvant or palliative chemotherapy
3. No previous radiotherapy
4. Presence of at least one unidimensionally measurable lesion (Appendix 2)
5. ECOG performance status of 0 or 1 (Appendix 3)
6. Charlson score ≤ 2 (Appendix 4)
7. Adequate bone marrow function (absolute neutrophil count ≥ 2 x 109/L, platelet count ≥ 100 x 109/L, and hemoglobin level ≥ 100 g/L), and adequate liver function (bilirubin level < two times the upper limit of normal, AST and/or ALT < three times the upper limit of normal, prothrombin time < 1.5 times control), and creatinine clearance ≥ 60 ml/min.
8. Absence of symptomatic CNS metastases (patients with cerebral metastases treated with brain irradiation may be included), severe cardiac arrhythmia or heart failure, second or third degree heart block or acute myocardial infarction within 4 months prior to study entry.
9. No major surgery or pleurodesis within 14 days prior to enrollment.
10. Life expectancy of at least 12 weeks.
11. No previous or concurrent malignancy, except inactive non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer if the patient has been disease-free for more than 5 years.
12. Written informed consent

Exclusion Criteria:

1. Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease).
2. Patients with clinically significant effusions.
3. Any other malignancies within 5 years that could affect therapy evaluation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; Gemcitabine 1,250 mg/sqm days 1 and 8 + Alimta 500 mg/sqm day 8, every 3 weeks	Drug: gemcitabine plus pemetrexed, paclitaxel plus gemcitabine; gemcitabine 1,250 mg/sqm days 1&8 + pemetrexed 500 mg/sqm day 8 paclitaxel 120 mg/sqm + gemcitabine 1,000 mg/sqm days 1&8
ACTIVE_COMPARATOR: B; Paclitaxel 120 mg/sqm days 1 and 8 + Gemcitabine 1,000 mg/sqm days 1 and 8, every 3 weeks	Drug: gemcitabine plus pemetrexed, paclitaxel plus gemcitabine; gemcitabine 1,250 mg/sqm days 1&8 + pemetrexed 500 mg/sqm day 8 paclitaxel 120 mg/sqm + gemcitabine 1,000 mg/sqm days 1&8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Response rate of patients treated with the gemcitabine plus Alimta regimen	after 3 cycles

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety of patients treated with gemcitabine plus Alimta regimen	at the end of treatment
Quality of life of patients treated with gemcitabine plus Alimta regimen	after 3 cyces

Collaborators and Investigators

• Sponsor: Southern Italy Cooperative Oncology Group
• Investigators: Principal Investigator: Pasquale Comella, MD, National Tumor Institute, Naples, Italy

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (ACTUAL): October 1, 2007
• Study Completion (ACTUAL): October 1, 2008

Study Registration Dates

• First Submitted: February 9, 2007
• First Submitted That Met QC Criteria: February 9, 2007
• First Posted (ESTIMATE): February 12, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): February 5, 2009
• Last Update Submitted That Met QC Criteria: February 4, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; gemcitabine; pemetrexed
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Gemcitabine; Paclitaxel; Pemetrexed
• Other Study ID Numbers: SICOG trial 0506