Maintaining ERBB Blockade in EGFR-mutated Lung Cancer

NCT02488694 | Terminated Phase 2 DMC

• 1 other identifier: AIO-TRK-0114
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to compare the efficacy of afatinib maintenance with pemetrexed maintenance following induction therapy with platinum/ pemetrexed in patients with metastatic epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC) progressing after first-line treatment with afatinib with respect to progression-free survival.

Conditions

Non-small-cell Lung Cancer With Somatic EGFR Mutations

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  The primary endpoint of this study is progression-free survival (RECIST 1.1).

  40 months

Secondary Outcomes (4)

• Overall survival

  40 months

• Objective response rate

  40 months

• Quality of Life

  40 month

• Safety (intensity and incidence of adverse events, graded according to US NCI CTCAE Version 4.03)

  40 month

Study Arms (2)

Arm A: Afatinib

EXPERIMENTAL

105 patients to be treated with afatinib

Drug: Afatinib

Arm B: Pemetrexed

ACTIVE COMPARATOR

105 patients to be treated with pemetrexed

Drug: Pemetrexed

Interventions

Afatinib DRUG

40 mg/d

Also known as: GIOTRIF®

Arm A: Afatinib

Pemetrexed DRUG

500 mg/m² i.v. on d1 of each 21-day cycle

Also known as: ALIMTA®

Arm B: Pemetrexed

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed diagnosis of non-small-cell lung cancer (NSCLC) with no curative therapeutic option. Patients with Stage IV (UICC 7th edition) disease or Stage IIIB disease not amenable to curative intent surgery or radiotherapy are enrolled. Patients with mixed histology are eligible if NSCLC is the predominant histology
• Documented somatic EGFR mutation as determined by medically accepted assay technology
• Patients with documented progression after response (CR/PR) or stable disease (SD) for at least 6 months of treatment with afatinib as first tyrosine kinase inhibitor (either given as first-line therapy or being switched to afatinib after up to 4 courses of platinum-based chemotherapy)
• Patients who have completed 3 or 4 cycles of cisplatin or carboplatin plus pemetrexed induction chemotherapy prior to randomization leading to documented response (CR/PR) or SD according to RECIST 1.1
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Male or female patient with age ≥18 years
• ECOG performance status ≤ 2
• Adequate organ and bone marrow function, defined as all of the following:
• Before the last cycle of induction chemotherapy or after hematopoietic recovery from the last cycle of induction chemotherapy:
• Absolute neutrophil count (ANC) ≥ 1,500 / mm3
• Platelet count ≥ 100,000 / mm3
• Creatinine clearance ≥ 45 ml / min (calculated according to Cockroft and Gault, or Tc99m-DPTA clearance or similar methodology). Patients with creatinine clearance of 45 to 79 ml/min should refrain from using NSAID at least 2 days before and 2 days after infusion of pemetrexed. Long-acting NSAID should be terminated 5 days before pemetrexed infusion.
• Total serum bilirubin ≤ 1.5 times upper limit of institutional normal (ULN)
• Serum aspartate amino transferase (AST) and serum alanine amino transferase (ALT) ≤ 3 times the upper limit of institutional normal (ULN) ( ≤ 5 times ULN if liver function abnormalities are due to underlying malignancy)
• Recovered from any previous therapy related toxicity to ≤ Grade 1 at study entry (except for stable sensory neuropathy ≤ Grade 2 and alopecia)

You may not qualify if:

• Systemic therapy for metastatic disease or relapse other than (a) first-line therapy with afatinib or (b) afatinib given as first EGFR-targeting agent following up to 4 courses of platinum-based chemotherapy with no disease progression between first-line chemotherapy and initiation of afatinib (prior adjuvant chemotherapy is allowed) and 3 to 4 cycles of induction chemotherapy with cisplatin or carboplatin and pemetrexed following afatinib failure
• Prior treatment with erlotinib, gefitinib or other investigational or approved EGFR-targeting small molecules or antibodies
• Known EGFR T790M mutation (analysis not mandatory)
• Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
• Extended radiotherapy within 4 weeks prior to randomization, except as follows:
• Palliative, limited local radiation to non-target lesions (e.g. isolated bone metastases) may be allowed up to 2 weeks prior to randomization, and
• single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling
• Active brain metastases except for the followings:
• Asymptomatic brain metastases incidentally found during screening process which do not require local treatment in the opinion of the investigator.
• Asymptomatic brain metastases for which local treatment has been given: stable for at least 4 weeks of lower dose corticosteroids (e.g., dexamethasone up to 4 mg/d) and/or non-enzyme-inducing anti-convulsants treatment before study randomization.
• Brain metastases controlled after surgery and/or radiotherapy
• Meningeal carcinomatosis
• Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, non-invasive bladder cancer, ductal carcinoma in situ of the breast, or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured. Definitively treated localized low/intermediate risk prostate cancer (Gleason score ≤ 7) is allowed when a rise in serum PSA level by ≥ 2 ng/mL above the nadir is excluded
• Known pre-existing interstitial lung disease
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug in the opinion of the investigator (e.g. Crohn's Disease, ulcerative colitis, chronic diarrhea, and malabsorption)

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Boehringer Ingelheim: collaborator

Study Sites (1)

Universitätsklinikum Essen

Essen, Germany

Location

Related Links

• Working Group for Medical Oncology (AIO) from the German Cancer Society (DKG)

MeSH Terms

Interventions

Afatinib; Pemetrexed

Intervention Hierarchy (Ancestors)

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

Study Officials

• Martin Schuler, Prof. Dr.

  Westdeutsches Tumorzentrum, Universitätsklinikum Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 2, 2015
• Study Start: November 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 9, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)