Pemetrexed in Advanced Non-Small-Cell Lung Cancer: at Progression vs Maintenance Therapy After Induction Chemotherapy

• Status: Terminated
• Trial end date: 2018-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Non-small-cell lung cancer (NSCLC) accounts for a majority (approximately 85%) of lung cancer cases. Patients with localized disease can be cured through surgery, but only 20 % are operable.For the majority of patients with advanced disease, palliative cytotoxic chemotherapy remains the recommended therapy. Chemotherapy prolongs survival and improves quality of life.

The recommended first-line therapy is 4-6 courses of a platinum in combination with a third generation compound (e.g. gemcitabine, vinorelbine, docetaxel, pemetrexed, paclitaxel). After first-line therapy, it has been recommended to observe the patients and offer second-line chemotherapy at disease progression.

Regimens for second-line therapy include docetaxel or pemetrexed monotherapy. Pemetrexed is less toxic and superior to gemcitabine in non-squamous NSCLC, whereas docetaxel is the recommended second-line therapy in squamous cell carcinoma.

The results of the studies of maintenance pemetrexed therapy are encouraging; the observed survival benefit is clinically relevant and relatively large considering the poor survival in patients with advanced NSCLC. Furthermore, pemetrexed appears to be well tolerated. There are, however, several limitations to the studies that have been conducted: Relatively few elderly patients and no PS 2 patients were enrolled - and not all patients on the control-arms received pemetrexed at progression.

The overall aim of this study is to investigate whether immediate maintenance pemetrexed therapy prolongs survival compared to observation and pemetrexed therapy at progression in patients with advanced NSCLC. Furthermore, it will be explored whether patients with 'performance status' 2 and elderly ≥ 70 years tolerate and benefit from maintenance therapy; and what characteristics and blood biomarkers are associated with sensitivity and tolerability of such therapy.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Norwegian University of Science and Technology
• Collaborator: St. Olavs Hospital
• Treatments: Pemetrexed

Criteria

Inclusion Criteria:

• Measureable disease according to the RECIST 1.1

• Previous radiotherapy is acceptable provided there are measurable, previously not irradiated lesions present

• Histologically or cytologically confirmed non-squamous non-small cell lung cancer

• Stage IIIB ineligible for curative therapy or stage IV disease

• ECOG Performance 0-2

• Adequate organ function defined as:

1. Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN), or AST and ALT ≤ 5 x ULN if liver function abnormalities are due to underlying malignancy.

2. Total serum bilirubin ≤ 1.5 x ULN

3. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

4. Platelets ≥ 100 x 109/L

5. Creatinine clearance > 45 ml/min

• Able to discontinue NSAIDs and ASA if reduced renal function

• All fertile patients should use safe contraception

• Written informed consent

Exclusion Criteria:

• prior systemic therapy for advanced non-small-cell lung cancer (including EGFR-TKI). Previous chemotherapy (e.g. adjuvant after surgery or for other cancer) is allowed if ≥ 3 months since the last course was administered.

• activating EGFR-mutation or ALK-translocation detected

• serious concomitant systemic disorders (for example active infection, unstable cardiovascular disease) that in the opinion of the investigator would compromise the patient's ability to complete the study or interfere with the evaluation of the efficacy and safety of the study treatment

• conditions - medical, social, psychological - which could prevent adequate information and follow-up

• clinically active cancer other than NSCLC

• known hypersensitivity or contraindications for the study drugs (vinorelbine, carboplatin, pemetrexed, B12, folate)

• pregnant or lactating women