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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Withdrawn; Phase 1

Conditions: Non-small Cell Lung Cancer

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

Study type: Interventional

Funder types: Other; NETWORK; Industry

Identifiers

NCT01836341

12-279

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Afatinib w Cisplatin Pemetrexed Chemoradiation

Experimental group

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

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Radiation: Radiation therapy

Drug: Afatinib

Drug: Carboplatin