Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation

NCT01836341 | Withdrawn Phase 1

• 1 other identifier: 12-279
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this Phase I study is to test the safety of combining afatinib with standard chemotherapy and radiation. The drug afatinib will be given before the chemotherapy and radiation therapy to shrink the tumor and evaluate how afatinib affects the patient. This study will then test the safety of afatinib at different dose levels when combined with the chemotherapy drugs cisplatin or carboplatin, and pemetrexed. These treatments will be given during radiation treatment and the drug afatinib will be continued after chemotherapy and radiation.

Conditions

Non-small Cell Lung Cancer

Keywords

Afatinib; Cisplatin; Carboplatin; Pemetrexed; Radiation therapy; EGFR mutation; 12-279

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dose

  This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.

  1 year

Secondary Outcomes (4)

• local control rate

  at 1 year and at 2 years

• tolerability of adjuvant afatinib

  at 3 months

• median progression free survival

  2 years

• median overall survival

  2 years

Study Arms (1)

Afatinib w Cisplatin Pemetrexed Chemoradiation

EXPERIMENTAL

induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation\* \*afatinib dose levels: 20mg daily, 30mg daily \& 40mg daily (3+3 design) Then adjuvant afatinib x 2 years

Drug: Afatinib; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Radiation: Radiation therapy

Interventions

Afatinib DRUG

Afatinib w Cisplatin Pemetrexed Chemoradiation

Cisplatin DRUG

Afatinib w Cisplatin Pemetrexed Chemoradiation

Carboplatin DRUG

Afatinib w Cisplatin Pemetrexed Chemoradiation

Pemetrexed DRUG

Afatinib w Cisplatin Pemetrexed Chemoradiation

Radiation therapy RADIATION

Afatinib w Cisplatin Pemetrexed Chemoradiation

Eligibility Criteria

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

You may qualify if:

• Unresectable or inoperable, stage III or locoregional recurrence without evidence of distant, metastatic disease
• Pathologic confirmation of NSCLC at MSKCC
• Documentation of a sensitizing EGFR mutation
• Age ≥ 18 years
• No contraindication to definitive thoracic radiation therapy with concurrent chemotherapy
• Adequate organ function as defined by:
• Calculated creatinine clearance≥ 45 mL/min (by Cockcroft-Gault)
• Total bilirubin less than 1.5 x ULN (unless known Gilbert's disease) and AST/ALT less than 3 x ULN
• Absolute neutrophil count greater than 1500/mm3
• Platelet count greater than 100,000/mm3
• Women of childbearing age must have a negative blood pregnancy test
• Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months there after

You may not qualify if:

• Prior chemotherapy or radiation therapy for this lung cancer (history of prior lung cancer that has been treated and deeded inactive by the clinician is acceptable)
• Ineligible for cisplatin or carboplatin per medical oncologist
• Ineligible for pemetrexed per medical oncologist
• Greater than minimal, exudative, or malignant pleural effusion
• Calculated creatinine clearance by Cockcroft \& Gault method ≤45 ml/min
• Unstable congestive heart failure
• Ejection fraction \<50% as assessed by MUGA or echocardiogram
• Interstitial lung disease
• Patient requiring on-going treatment with a potent inhibitor (cyclosporin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital with quinidine, ritonavir, valspodar, verapamil) or inducer of P-gp (St. John's wort or rifampin)
• Women who are breastfeeding

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Boehringer Ingelheim: collaborator
• National Comprehensive Cancer Network: collaborator

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib; Cisplatin; Carboplatin; Pemetrexed; Radiotherapy

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)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Therapeutics

Study Officials

• Jamie E. Chaft, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2013
• First Posted: April 19, 2013
• Study Start: April 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: December 19, 2013

Record last verified: 2013-12