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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborators:
Boehringer Ingelheim
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01836341
First received: April 17, 2013
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Non-small Cell Lung Cancer
Drug: Afatinib
Drug: Cisplatin
Drug: Carboplatin
Drug: Pemetrexed
Radiation: Radiation therapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.


Secondary Outcome Measures:
  • local control rate [ Time Frame: at 1 year and at 2 years ] [ Designated as safety issue: No ]
    will be determined as the proportion of patients who start the concurrent phase who are alive and free of local failure.

  • tolerability of adjuvant afatinib [ Time Frame: at 3 months ] [ Designated as safety issue: No ]
    Tolerability will be defined by in terms of dose reductions, delays and discontinuations of patients who have not had disease progression or death.

  • median progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    PFS is defined as the duration of time from start of treatment to time of progression of disease or death, whichever occurs first.

  • median overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    will be calculated using Kaplan-Meier estimates among all patients enrolled.


Enrollment: 0
Study Start Date: April 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01836341

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

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01836341     History of Changes
Other Study ID Numbers: 12-279
Study First Received: April 17, 2013
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Afatinib
Cisplatin
Carboplatin
Pemetrexed
Radiation therapy
EGFR mutation
12-279

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 26, 2014