Testing the Addition of an Antibody to Standard Chemoradiation followed by the Antibody for One Year to Standard Chemoradiation followed by One Year of the Antibody in Patients with Unresectable Stage III Non-Small Cell Lung Cancer

Active:	No
Cancer Type:	Lung Cancer	NCT ID:	NCT04092283
Trial Phases:	Phase III	Protocol IDs:	EA5181 (primary) EA5181 NCI-2019-06124
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	ECOG-ACRIN Cancer Research Group
NCI Full Details:	http://clinicaltrials.gov/show/NCT04092283

Summary

This phase III trial studies how well an antibody (durvalumab) with chemotherapy and radiation therapy (chemoradiation) works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to see if adding durvalumab to standard chemoradiation followed by additional durvalumab can extend patients life and/or prevent the tumor from coming back compared to the usual approach of chemoradiation alone followed by durvalumab.

Objectives

PRIMARY OBJECTIVE:
I. To evaluate whether there is an improvement in overall survival with concomitant chemotherapy/radiation therapy/MEDI4736 (durvalumab) followed by one year (12 cycles) of MEDI4736 (durvalumab) as compared to concomitant chemotherapy/radiation followed by one year (12 cycles) of MEDI4736 (durvalumab).

SECONDARY OBJECTIVES:
I. To evaluate the difference in response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria to assess whether or not MEDI4736 (durvalumab) added to concomitant chemo/radiation results in an improvement in response rates.
II. To evaluate any difference in progression free survival (PFS) with concomitant chemotherapy/radiation therapy/MEDI4736 (durvalumab) followed by one year (12 cycles) of MEDI4736 (durvalumab) as compared to concomitant chemotherapy/radiotherapy followed by one year of MEDI4736 (durvalumab).
III. To evaluate whether the incidence of recurrence and recurrence pattern is affected by giving MEDI4736 (durvalumab) during chemo/radiation.
IV. To evaluate any difference in toxicity when MEDI4736 (durvalumab) is added to concomitant chemo/radiation using the Common Terminology Criteria for Adverse Events (CTCAE).

OUTLINE:
STEP 1 (CONCURRENT THERAPY): Patients are randomized to 1 of 2 arms.

ARM A: Patients receive durvalumab intravenously (IV) over 60 minutes on days 1 and 15 of cycle 1 and day 1 of cycle 2. Patients also receive 1 of 3 treatment regimens per investigator choice: 1) etoposide IV over 60 minutes on days 1-5 and cisplatin IV over 60 minutes on days 1 and 8 every 28 days for 2 cycles; 2) pemetrexed disodium IV over 60 minutes and cisplatin IV over 60-120 minutes on day 1 every 21 days for 2 cycles; or 3) paclitaxel IV over 60 minutes and carboplatin IV over 30 minutes on day 1 every 7 days for 6 cycles. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of chemotherapy, patients receive radiation therapy 5 days a week for 6 weeks.

ARM B: Patients receive 1 of 3 investigator's choice treatment regimens and radiation therapy as in Arm A.

STEP 2 (CONSOLIDATION THERAPY): Within 14 days after the last dose of radiation (from Step 1), all patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, every 6 months if 2-5 years from study entry, and then yearly for years 5-10 from study entry.

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