Phase Ib Study of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Non-small Lung Cancer (NSCLC) With Dual Immune Checkpoint Inhibition
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03275597|
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : January 7, 2021
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Non-small Cell Lung Cancer Stage IV||Drug: Durvalumab Drug: Tremelimumab Radiation: Stereotactic Body Radiotherapy||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.|
|Actual Study Start Date :||February 20, 2018|
|Estimated Primary Completion Date :||July 2022|
|Estimated Study Completion Date :||October 2022|
Experimental: SBRT followed by Durvalumab+Tremelimumab
Therapeutic Interventions Stereotactic Body Radiotherapy (SBRT) to all sites of disease between 30 and 50 Gy in five fractions administered over two weeks.
Investigational Product(s), Dose, and Mode of Administration: to begin 7 days (+/- 3 days) after radiation Durvalumab 1500 mg via infusion Q4W (equivalent to 20 mg/kg Q4W) until disease progression in patients > 30 kg Tremelimumab 300 mg via infusion (equivalent to 4 mg/kg) in one dose in patients >30 kg Weight-based dosing should be utilized for patients ≤30 kg; durvalumab 20 mg/kg Q4W and tremelimumab 4 mg/kg
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.
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.
Radiation: Stereotactic Body Radiotherapy
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.
- Safety and tolerability of SBRT followed by combined durvalumab and tremelimumab, assessed by CTCAE v4.03 [ Time Frame: Up to 3 years ]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.
- Progression Free Survival assessed with RECIST 1.1 tumor assessments [ Time Frame: Up to 4 years ]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.
- Overall Survival assessed with RECIST 1.1 tumor assessments [ Time Frame: Up to 4 years ]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.
- Evaluate immune response [ Time Frame: Up to 4 years ]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.
- Evaluate PD-L1 expression [ Time Frame: Up to 4 years ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275597
|Contact: Cancer Connectfirstname.lastname@example.org|
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Cancer Connect 800-622-8922 email@example.com|
|Principal Investigator: Michael Bassetti, MD, PhD|
|Principal Investigator:||Michael Bassetti, MD, PhD||University of Wisconsin, Madison|