Clinical Trials /

Afatinib With CT and RT for EGFR-Mutant NSCLC

NCT01553942

Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that study doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not yet approved the drug for the patients type of cancer or for any use outside of research studies. Chemotherapy and radiation is the standard treatment for the patients with stage III non-small cell lung cancer (NSCLC). For people with epidermal growth factor receptor (EGFR) mutations, adding a type of drug called a tyrosine kinase inhibitor (TKI) can help increase the response to treatment. Afatinib is a tyrosine kinase inhibitor. It has been studied in a previous research study in participants with more advanced NSCLC. Results from that study indicate it may be helpful in treating NSCLC with EGFR mutations. In this study, patients with stage III NSCLC and EGFR mutations will receive the standard treatment of radiation and chemotherapy. If possible, the patients tumor will be removed by surgery. Afatinib will be given before radiation and chemotherapy and after surgery. The aim of giving afatinib before radiation therapy is to try to shrink the tumor. This may make the radiation therapy more effective since radiation therapy tends to work better on smaller tumors. The goal of this study is to see if adding afatinib to standard treatment helps to improve the response to treatment.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Afatinib With CT and RT for EGFR-Mutant NSCLC
  • Official Title: Afatinib Sequenced With Concurrent Chemotherapy and Radiation in EGFR-Mutant Non-Small Cell Lung Tumors: The ASCENT Trial

Clinical Trial IDs

  • ORG STUDY ID: 11-464
  • NCT ID: NCT01553942

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
AfatinibAfatinib
CisplatinAfatinib
PemetrexedAfatinib

Purpose

This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that study doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not yet approved the drug for the patients type of cancer or for any use outside of research studies. Chemotherapy and radiation is the standard treatment for the patients with stage III non-small cell lung cancer (NSCLC). For people with epidermal growth factor receptor (EGFR) mutations, adding a type of drug called a tyrosine kinase inhibitor (TKI) can help increase the response to treatment. Afatinib is a tyrosine kinase inhibitor. It has been studied in a previous research study in participants with more advanced NSCLC. Results from that study indicate it may be helpful in treating NSCLC with EGFR mutations. In this study, patients with stage III NSCLC and EGFR mutations will receive the standard treatment of radiation and chemotherapy. If possible, the patients tumor will be removed by surgery. Afatinib will be given before radiation and chemotherapy and after surgery. The aim of giving afatinib before radiation therapy is to try to shrink the tumor. This may make the radiation therapy more effective since radiation therapy tends to work better on smaller tumors. The goal of this study is to see if adding afatinib to standard treatment helps to improve the response to treatment.

Detailed Description

      Study treatment will be divided into 5 stages:

      Stage 1-induction, consisting of afatinib for two 4-week cycles. Afatinib is a pill that the
      patient takes by mouth once per day. The patient will receive a study drug diary in which to
      record the doses of afatinib.

      Stage 2-concurrent radiation and chemotherapy with cisplatin/pemetrexed for two 3-week
      cycles.

      Stage 3-Surgery to remove tumor for participants whose tumor can be removed by surgery. This
      will be done about 4-6 weeks after finishing radiation and chemotherapy. The exact timing
      will depend upon how quickly the patient recovers from side effects of the radiation and
      chemotherapy. The investigators will use a piece of the patients tumor removed by surgery for
      research tests to look for biomarkers such as genes and proteins that may be associated with
      response to afatinib, chemotherapy or radiation.

      Stage 4-Chemotherapy after surgery (adjuvant chemotherapy). The patients doctor will decide
      if the patient will receive chemotherapy after the patients surgery but before receiving
      consolidation with afatinib. If the patient does receive this, it will start 6-12 weeks after
      surgery or finishing radiation if the patient does not have surgery. The chemotherapy will be
      the same as that received along with the radiation therapy.

      Stage 5-Consolidation with afatinib for twenty-six 4-week cycles (2 years) for participants
      who responded to the 2 cycles of induction afatinib.

      The investigators would like to keep track of the patients medical condition and status of
      the patients disease for up to 5 years after the patient stops study treatment. Keeping in
      touch with the patients and checking on the patients condition every year helps the
      investigators look at the long-term effects of the research study. The patients will be asked
      to have CT scans as follows:

        -  Every 3 months for the first year after stopping study treatment

        -  Every 6 months for years 2-4 after stopping study treatment

        -  Once per year in year 5 after stopping study treatment
    

Trial Arms

NameTypeDescriptionInterventions
AfatinibExperimentalAfatinib
  • Afatinib
  • Cisplatin
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed stage IIIA NSCLC

          -  Measurable disease

          -  Have lung cancer harboring an EGFR mutation

          -  Must be evaluated by a medical oncologist, radiation oncologist and thoracic surgeon
             within 4 weeks of enrollment into study to document that they are a candidate for
             chemoradiation and for consideration of surgical resection (not required to be a
             surgical candidate)

        Exclusion Criteria:

          -  Pregnant or breastfeeding

          -  Prior EGFR TKI therapy

          -  Prior treatment with radiation to the thoracic region (including breast irradiation)

          -  Known pre-existing interstitial lung disease

          -  Significant or recent gastrointestinal disorders with diarrhea as a major symptom

          -  History or presence of relevant cardiovascular abnormalities

          -  Any other concomitant serious illness or organ system dysfunction

          -  Active hepatitis B, C or known HIV carrier

          -  Known or suspected active drug or alcohol use

          -  Known hypersensitivity to afatinib, cisplatin, or pemetrexed

          -  Concomitant treatment with strong inhibitor of P-gp

          -  History of an active malignancy within the last 3 years
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate
Time Frame:2 years
Safety Issue:
Description:Assess the response rate to induction afatinib.

Secondary Outcome Measures

Measure:2 Year Progression-Free Survival
Time Frame:2 years
Safety Issue:
Description:Estimate the 2-year progression-free survival (PFS)
Measure:Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame:2 years
Safety Issue:
Description:Describe the number of patients that have side effects of various types from the study treatment
Measure:Unresectable Disease Converted to Operable Cases
Time Frame:2 years
Safety Issue:
Description:Estimate the proportion of patients with initially unresectable disease that can be converted to operable cases
Measure:Locoregional Tumor Control Rates
Time Frame:2 years
Safety Issue:
Description:Estimate 2-year locoregional tumor control rates, distant metastasis rates and overall survival rates, as well as median overall survival (OS)
Measure:Evaluation of EGFR Mutation Status and other genotypes
Time Frame:2 years
Safety Issue:
Description:Evaluate the status of various relevant genes such as EGFR, MET, and other genes that might be related to response or resistance to afatinib, and assess relationship to clinical outcomes

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • NSCLC

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