Back to resultsAfatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
Primary Purpose
Non-small Cell Lung Cancer
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Afatinib
Cisplatin
Carboplatin
Pemetrexed
Radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring Afatinib, Cisplatin, Carboplatin, Pemetrexed, Radiation therapy, EGFR mutation, 12-279
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Afatinib w Cisplatin Pemetrexed Chemoradiation
Arm Description
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
Outcomes
Primary Outcome Measures
maximum tolerated dose
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
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
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
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
will be calculated using Kaplan-Meier estimates among all patients enrolled.
Full Information
NCT ID
NCT01836341
First Posted
April 17, 2013
Last Updated
December 18, 2013
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Boehringer Ingelheim, National Comprehensive Cancer Network
1. Study Identification
Unique Protocol Identification Number
NCT01836341
Brief Title
Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
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 Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Withdrawn
Study Start Date
April 2013 (undefined)
Primary Completion Date
April 2015 (Anticipated)
Study Completion Date
April 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Boehringer Ingelheim, National Comprehensive Cancer Network
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
Afatinib, Cisplatin, Carboplatin, Pemetrexed, Radiation therapy, EGFR mutation, 12-279
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Afatinib w Cisplatin Pemetrexed Chemoradiation
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Afatinib
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Type
Radiation
Intervention Name(s)
Radiation therapy
Primary Outcome Measure Information:
Title
maximum tolerated dose
Description
This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
local control rate
Description
will be determined as the proportion of patients who start the concurrent phase who are alive and free of local failure.
Time Frame
at 1 year and at 2 years
Title
tolerability of adjuvant afatinib
Description
Tolerability will be defined by in terms of dose reductions, delays and discontinuations of patients who have not had disease progression or death.
Time Frame
at 3 months
Title
median progression free survival
Description
PFS is defined as the duration of time from start of treatment to time of progression of disease or death, whichever occurs first.
Time Frame
2 years
Title
median overall survival
Description
will be calculated using Kaplan-Meier estimates among all patients enrolled.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jamie E. Chaft, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Links:
URL
http://www.mskcc.org/
Description
Memorial Sloan-Kettering Cancer Center
Learn more about this trial
Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
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