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Report for Clinical Trial NCT03275597

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Comprehensive Stereotactic Body Radiotherapy (SBRT) to All Sites of Oligometastatic Non-small Cell Lung Cancer (NSCLC) Combined With Durvalumab (MEDI4736) and Tremelimumab Dual Immune Checkpoint Inhibition.

This is a phase Ib study to evaluate safety and tolerability of dual checkpoint inhibition (DCI) of durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) with SBRT in the treatment of oligometastatic NSCLC. This study will examine the sequential delivery of SBRT to all disease sites followed by combination of durvalumab and tremelimumab for patients for whom the goal is ablating all known sites of disease. The investigators anticipate that for many participants this will be the first line-therapy. Participants who have received prior-platinum-based chemotherapy and/or any line of prior chemotherapy are eligible. Prior immunotherapy treatment is not allowed.

NCT03275597 Non-small Cell Lung Cancer Non-small Cell Lung Cancer Stage IV
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

3 Interventions

Name: Durvalumab

Description: Durvalumab is an FDA-approved immunotherapy for cancer. Durvalumab is a human monoclonal antibody (mAb) of the immunoglobulin G (IgG) 1 kappa subclass that inhibits binding of PD-L1 and is being developed by AstraZeneca/MedImmune for use in the treatment of cancer.
Type: Drug
Group Labels: 1

SBRT followed by Durvalumab+Tremelimumab

Name: Tremelimumab

Description: Tremelimumab is a monoclonal antibody against CTLA-4. It is an IgG 2 kappa isotype mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) also known as CD152 (cluster of differentiation 152). This is an immunomodulatory therapy (IMT) that is being developed by AstraZeneca for use in the treatment of cancer.
Type: Drug
Group Labels: 1

SBRT followed by Durvalumab+Tremelimumab

Name: Stereotactic Body Radiotherapy

Description: SBRT is a highly conformal approach to the delivery of radiation therapy, maximizing radiation dose to the tumor while minimizing dose to nearby normal tissues.
Type: Radiation
Group Labels: 1

SBRT followed by Durvalumab+Tremelimumab


Primary Outcomes

Description: Toxicities will be summarized by type and severity in tabular format. Toxicity rates (grade 2, grade 3, grade 4, grade ≥ 2, grade ≥ 3, etc.) will be calculated and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method.

Measure: Safety and tolerability of SBRT followed by combined durvalumab and tremelimumab, assessed by CTCAE v4.03

Time: Up to 3 years

Secondary Outcomes

Description: Progression-free survival (PFS) will be defined as the difference (in months) between the date of study enrollment and the date of disease progression or death due to any cause. PFS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median PFS. PFS assessed with RECIST 1.1 tumor assessments. The effect of DCI with durvalumab and tremelimumab will be compared against historical controls for a 95% CI and p-value.

Measure: Progression Free Survival assessed with RECIST 1.1 tumor assessments

Time: Up to 4 years

Description: Overall survival (OS) will be defined as the difference (in months) between the date of study enrollment to the date death due to any cause. OS will be analyzed using the Kaplan-Meier method, and the Brookmeyer-Crowley method will be used to construct the 95% confidence interval for the median OS. The effect of DCI with durvalumab tremelimumab will be compared against historical controls for a 95% CI and p-value.

Measure: Overall Survival assessed with RECIST 1.1 tumor assessments

Time: Up to 4 years

Other Outcomes

Description: Determine whether immune response on biopsy sections or circulating tumor cells is increased following SBRT. The paired McNemar's test will be used to compare with subjects with an immune response between assessment time point.

Measure: Evaluate immune response

Time: Up to 4 years

Description: Determine whether PD-L1 expression on biopsy sections or circulating tumor cells is increased following SBRT. PD-L1 expression will be summarized in terms of means, standard deviation, median and range. Absolute and percentage changes in PD-L1 expression levels between the pre-SBRT versus post-SBRT assessment will be calculated and evaluated using a paired t-test.

Measure: Evaluate PD-L1 expression

Time: Up to 4 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 L858R

exon 19 deletion or exon 21 L858R) or ALK rearrangement. --- L858R ---



HPO Nodes


HPO: