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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01836341
• Other study ID #: 12-279
• Status: Withdrawn
• Phase: Phase 1
• First received: April 17, 2013
• Last updated: December 18, 2013
• Start date: April 2013
• Est. completion date: April 2015

Study information

• Verified date: December 2013
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Afatinib

• Cisplatin

• Carboplatin

• Pemetrexed

Radiation:
• Radiation therapy

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Boehringer Ingelheim, National Comprehensive Cancer Network

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose	This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.	1 year	No
Secondary	local control rate	will be determined as the proportion of patients who start the concurrent phase who are alive and free of local failure.	at 1 year and at 2 years	No
Secondary	tolerability of adjuvant afatinib	Tolerability will be defined by in terms of dose reductions, delays and discontinuations of patients who have not had disease progression or death.	at 3 months	No
Secondary	median progression free survival	PFS is defined as the duration of time from start of treatment to time of progression of disease or death, whichever occurs first.	2 years	No
Secondary	median overall survival	will be calculated using Kaplan-Meier estimates among all patients enrolled.	2 years	No

External Links

•   Memorial Sloan-Kettering Cancer Center