Induction Therapy With Intercalated Tyrosine Kinase Inhibitor (TKI) and Chemotherapy in NSCLC With Activating Epidermal Growth Factor Receptor (EGFR) Mutation in Stages II-IIIB

NCT02326285 | Terminated Phase 2

• 3 other identifiers: AIO-TRK-02142014-005595-28IISR ESR-14-10598
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed as a single arm, un-controlled, open-label, multi-center hypothesis generating two-stage phase II trial. It is based on the assumption that the proposed treatment scheme doubles the rate of pathologic complete remission in Mutated epidermal growth factor receptor (EGFRmt) + NSCLC patients compared to historical control data from standard treatments. Patients with NSCLC and activating EGFR mutation in stages II, IIIA and IIIB eligible for induction therapy with docetaxel and cisplatin and gefitinib Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.

Conditions

Non-squamous Non-small Cell Lung Cancer Stage II; Non-squamous Non-small Cell Lung Cancer Stage IIIA; Non-squamous Non-small Cell Lung Cancer Stage IIIB; Activating EGFR Mutation; NSCLC

Keywords

induction therapy; NSCLC; Non-small Cell Lung Cancer; curative surgery

Outcome Measures

Primary Outcomes (1)

• pathologic complete remission rate (pCR rate)

  The primary objective of the study is to assess the pathologic complete remission rate after induction therapy with gefitinib d -12 to d-1 followed by docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 q21 and intercalated gefitinib 250 mg d4 to d20 (cycle 1 and 2) and d4-17 (for cycle3), in order to demonstrate feasibility and efficacy of this treatment scheme. It is expected to achieve a pCR ≥30% regression grade IIB and III (Junker criteria) compared to historical controls in the mediastinal lymph nodes.

  12 weeks (after 3 cycles and surgery) after enrollment

Secondary Outcomes (9)

• Adverse Events (AEs) / Serious adverse events (SAEs)

  30 months

• Surgical R0 resection rate

  30 month

• Response: radiologic response based on CT

  30 month

• progression free survival (PFS)

  30 month

• Overall survival (OS)

  30 month

Study Arms (1)

Treatment phase

EXPERIMENTAL

Enrolled patients will be treated with 250mg/day Gefitinib for 11 days (day -12 until day -1) followed by 3 cycles (length 21 days) of chemotherapy with docetaxel (75mg/m2 d1) and cisplatin (50 mg/m2 d1+2) combined with intercalated gefitinib (250mg/day, d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.

Drug: Gefitinib; Drug: docetaxel; Drug: cisplatin; Procedure: Surgery

Interventions

Gefitinib DRUG

Patients will be treated for 12 days with gefitinib 250 mg/day p.o. (d -12 to -1) and induced with chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3). Surgery is planned in the 4th week after d1 of the last cycle.

Also known as: IRESSA ®

Treatment phase

docetaxel DRUG

chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3).

Treatment phase

cisplatin DRUG

chemotherapy docetaxel 75 mg/m2 and cisplatin 50 mg/m2 d1+2 and intercalated gefitinib 250 mg/day d4-20 (cycle 1 and 2) and d4-17 (for cycle3).

Treatment phase

Surgery PROCEDURE

Surgery should be performed in the 4th or at the latest 5th week after d1 of the last cycle of chemotherapy (d64 to 78).

Treatment phase

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed non-squamous non-small-cell lung cancer (NSCLC) stage II, IIIA and IIIB detected preoperatively by adequate methods and activating EGFR mutation in exons 18-21 and deemed to be able to undergo curative surgery after induction therapy. Stage should be confirmed by PET-CT as well as adequate mediastinal staging. MRI of the brain to exclude CNS metastases is mandatory.
• At least one unidimensionally measurable lesion meeting RECIST criteria (version 1.1);
• Performance status of 0 to 1 on the ECOG scale;
• Estimated life expectancy of at least 12 weeks;
• Patients aged ≥ 18 years;
• Adequate organ function including the following:
• Adequate bone marrow reserve:
• absolute neutrophils (segmented and bands) count (ANC) ≥1.5x109/L;
• platelets ≥100x109/L;
• haemoglobin ≥9 g/dL.
• Hepatic:
• bilirubin ≤ 1xULN;
• alkaline phosphatase (AP);
• aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5xULN.
• Renal:

You may not qualify if:

• EGFR wild type configuration;
• EGFR resistance mutations (i.e. T790M);
• Significant cardiovascular disease, such as uncontrolled hypertension, myocardial infarction within the last 6 months, unstable angina pectoris, CHF ≥ NYHA 2, serious arrhythmia, significant peripheral vascular disease;
• Pre-existing neuropathic ≥ grade 2;
• Patients with confirmed HIV infection. HIV testing is not mandatory.
• Prior history of malignancy except for basal cell carcinoma or carcinoma in situ of the cervix, and with the exception of other malignancies after curative treatment with an interval of at least 3 years.
• Lactating or pregnant woman, woman of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are implants, injectable contraceptives, combined oral contraceptives, intrauterine devices (only hormonal devices), sexual abstinence or vasectomy of the partner). Woman of childbearing potential must have a negative pregnancy test (serum β-HCG) at visit 1.
• Any other chemotherapy at start;
• Treatment with other experimental drugs during the course of the study or within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
• Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial;
• Parallel participation in another clinical trial or participation in another clinical trial within the last 30 days or 7 half-lifes, whatever is of longer duration, prior study start;
• Patient has already been included in this trial;
• Patients who do not understand the nature, the scope and the consequences of the clinical trial;
• Affected persons who might be dependent on the sponsor or the investigator.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• AstraZeneca: collaborator

Study Sites (1)

Pius-Hospital

Oldenburg, 26121, Germany

Location

Related Links

• AIO - Working Group for Medical Oncology from the German Cancer Society

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; Docetaxel; Cisplatin; Surgical Procedures, Operative

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Frank Griesinger, Prof. Dr.

  Universitätsklinik für Innere Medizin-Onkologie, Pius-Hospital, Oldenburg

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 29, 2014
• Study Start: November 1, 2015
• Primary Completion: March 28, 2017
• Study Completion: January 1, 2018
• Last Updated: January 23, 2018

Record last verified: 2018-01

Locations

DE (1)