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

NCT02004184 | Terminated Phase 3 DMC

• 2 other identifiers: 2013/6452013-001237-41
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Carcinoma, Non-small-cell Lung

Keywords

Pemetrexed; drug therapy

Outcome Measures

Primary Outcomes (1)

• overall survival

  All patients will be followed until death of any reason - assessed up to 24 months after inclusion in the study.

  2 years

Secondary Outcomes (3)

• progression free survival

  2 years

• Toxicity

  2 years

• Health related quality of life

  2 years

Other Outcomes (4)

• Overall survival in elderly and PS 2 patients

  2 years

• Associations between clinical characteristics and blood biomarkers - and outcomes of therapy

  2 years

• Toxicity in elderly and PS 2 patients

  2 years

Study Arms (2)

maintenance pemetrexed

EXPERIMENTAL

maintenance pemetrexed immediately after induction chemotherapy

Drug: maintenance pemetrexed

pemetrexed at progression

ACTIVE COMPARATOR

observation and pemetrexed therapy at disease progression

Drug: pemetrexed at progression

Interventions

maintenance pemetrexed DRUG

500 mg/m2 Body Surface Area is administered intravenously every 3 weeks

Also known as: Alimta

maintenance pemetrexed

pemetrexed at progression DRUG

500 mg/m2 Body Surface Area is administered intravenously every 3 weeks

Also known as: Alimta

pemetrexed at progression

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Total serum bilirubin ≤ 1.5 x ULN
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator

Study Sites (1)

St Olavs Hospital

Trondheim, Norway

Location

Related Publications (2)

• Halvorsen TO, Stokke K, Killingberg KT, Raj SX, Sorhaug S, Brustugun OT, Flotten O, Helbekkmo N, Hornslien K, Madebo T, Fluge S, Gronberg BH. Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC. Acta Oncol. 2020 Sep;59(9):1051-1057. doi: 10.1080/0284186X.2020.1778179. Epub 2020 Jun 16.

  PMID: 32543258 RESULT

• Stokke K, Sandvei MS, Gronberg BH, Slaaen M, Killingberg KT, Halvorsen TO. Prognostic Value of Post First-Line Chemotherapy Glasgow Prognostic Score in Advanced Non-Small Cell Lung Cancer. Clin Med Insights Oncol. 2022 Mar 22;16:11795549221086578. doi: 10.1177/11795549221086578. eCollection 2022.

  PMID: 35342321 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Bjørn H Grønberg, MD PhD

  Norwegian University of Science and Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2013
• First Posted: December 9, 2013
• Study Start: December 1, 2013
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: June 23, 2020

Record last verified: 2020-06

Locations

NO (1)