Neoadjuvant Afatinib in Early Stage Non Small Cell Lung Cancer. (REMNANT)

Resectable EGFR Mutant NSCLC With (or Without) Afatinib as Neoadjuvant Treatment; REMNANT an Exploratory Study of the EORTC Lung Cancer Group

This is a multicenter, randomized, 1:1, non-comparative phase II trial. Patients with early stage NSCLC will be randomized between ARM A: neoadjuvant afatinib followed by surgery and ARM B: immediate surgery with curative intent.

Study Overview

• Status: Suspended
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Afatinib; Procedure: Immediate surgery

Detailed Description

This is a multicenter, prospective, open-label, randomized, non-comparative, two-arm phase II trial aiming to evaluate afatinib treatment in pre-operative setting in patients with EGFR mutated NSCLC.

After signing of the informed consent, patients will be registered and screened for eligibility and upon confirmation of all eligibility criteria, patients will be randomized 1:1 to:

• Arm A: once daily afatinib at a dose of 40 mg for 8 weeks followed by surgery with curative intent (anatomical resection and systematic lymph node dissection).
• Arm B: immediate surgery with curative intent (anatomical resection and systematic lymph node dissection).

Response evaluation in the pre-operative arm will be performed through CT scans at baseline, 4 and 8 weeks.

The first 5 patients enrolled in arm A will be part of a safety run-in to check that afatinib treatment doesn't delay surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Histological or cytological diagnosis of NSCLC;

• Patients considered operable and with resectable tumor with curative intent (anatomical resection and systematic lymph node dissection) based on evaluation by a thoracic multi-disciplinary team composed of at least a thoracic surgeon, oncologist and radiologist;
• Stage I-III (T1a-3, N0-1, M0 according to UICC version 7) NSCLC by local staging criteria potentially treatable by radical (curative) surgery. Patients with T1 tumor at baseline will be limited to 20%;
• Radiologically measurable disease according to RECIST criteria 1.1; assessed by chest and upper abdomen CT scan within 2 weeks (+1 week) prior to registration); brain CT scan or MRI according to local practice;
• No prior treatment for NSCLC is allowed;
• Adequate tissue in terms of quality and quantity for EGFR local testing.

Exclusion Criteria:

• no adequate bone marrow function within 2 weeks prior to randomization
• no adequate liver function. Patients with Gilbert's syndrome total bilirubin must be below 4 times institutional upper limit of normal; within 2 weeks prior to randomization
• no adequate renal function within 2 weeks prior to randomization
• known positivity to human immunodeficiency virus (HIV), hepatitis B or hepatitis C;
• known history of allergic reactions attributed to compounds of similar chemical or biological composition;
• history of a hematologic or primary solid tumor malignancy, unless no evidence of that disease for 5 years, except pT1-2 prostatic cancer Gleason score < 6, superficial bladder cancer, non melanoma skin cancer or carcinoma in situ of the cervix;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neo adjuvant afatinib; once daily afatinib at a dose of 40 mg for 8 weeks followed by surgery with curative intent (anatomical resection and systematic lymph node dissection).	Drug: Afatinib; once daily afatinib at a dose of 40 mg for 8 weeks; Procedure: Immediate surgery; anatomical resection and systematic lymph node dissection
Active Comparator: Immediate surgery; immediate surgery with curative intent (anatomical resection and systematic lymph node dissection).	Procedure: Immediate surgery; anatomical resection and systematic lymph node dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in cT-stage	decrease in cT-stage descriptor measured according to RECIST 1.1	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	proportion of patients whose response is either complete response (CR) or partial response (PR) using RECIST 1.1;	8 weeks
Change in surgical treatment intent and technique		8 weeks

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Principal Investigator: Sanjay Popat, PhD, Royal Marsden NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 11, 2015
• First Posted (Estimate): June 12, 2015

Study Record Updates

• Last Update Posted (Estimate): January 22, 2016
• Last Update Submitted That Met QC Criteria: January 21, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: NSCLC; Randomized; Phase II; Early stage; EGFR mutated
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: EORTC-08115