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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Afatinib; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Radiation: Radiation therapy	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Dose-Finding Study Of Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
Study Start Date :	April 2013
Estimated Primary Completion Date :	April 2015
Estimated Study Completion Date :	April 2015

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Afatinib w Cisplatin Pemetrexed Chemoradiation; 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

Outcome Measures

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Primary Outcome Measures :

1. maximum tolerated dose [ Time Frame: 1 year ]
   This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.

Secondary Outcome Measures :

1. local control rate [ Time Frame: at 1 year and at 2 years ]
   will be determined as the proportion of patients who start the concurrent phase who are alive and free of local failure.
2. tolerability of adjuvant afatinib [ Time Frame: at 3 months ]
   Tolerability will be defined by in terms of dose reductions, delays and discontinuations of patients who have not had disease progression or death.
3. median progression free survival [ Time Frame: 2 years ]
   PFS is defined as the duration of time from start of treatment to time of progression of disease or death, whichever occurs first.
4. median overall survival [ Time Frame: 2 years ]
   will be calculated using Kaplan-Meier estimates among all patients enrolled.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

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Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Boehringer Ingelheim

National Comprehensive Cancer Network

Investigators

Principal Investigator:	Jamie E. Chaft, MD	Memorial Sloan Kettering Cancer Center

More Information

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Additional Information:

Memorial Sloan-Kettering Cancer Center 

Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01836341 History of Changes
Other Study ID Numbers:	12-279
First Posted:	April 19, 2013
Last Update Posted:	December 19, 2013
Last Verified:	December 2013

Keywords provided by Memorial Sloan Kettering Cancer Center:

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

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic	Bronchial Neoplasms; Cisplatin; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors