Trials / Terminated
TerminatedNCT04538378
Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors
Phase II Trial of Olaparib (LYNPARZA) Plus Durvalumab (IMFINZI) in EGFR-Mutated Adenocarcinomas That Transform to Small Cell Lung Cancer (SCLC) and Other Neuroendocrine Tumors
- Status
- Terminated
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 4 (actual)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
Background: Lung cancers with epidermal growth factor receptor (EGFR) mutations may develop resistance to therapies targeting this protein by evolving/being transformed into small cell or neuroendocrine cancers. There are no standard treatments for it. Researchers want to see if a new combination of drugs can help. Objective: To see if the combination of durvalumab and olaparib will cause tumors to shrink. Eligibility: Adults age 18 and older who had EGFR-mutated non-small-cell lung carcinoma (NSCLC) that was treated and now transformed to SCLC or another neuroendocrine tumor. Design: Participants will be screened under a separate protocol. They may have a tumor biopsy. Participants will have a physical exam. They will have a review of their symptoms, their medicines, and their ability to do their normal activities. They will have blood tests. They will have an electrocardiogram to evaluate their heart. Participants will have a computed tomography (CT) scan, a series of x-rays taken of parts of the body. Participants will get durvalumab on Day 1 of each 28-day cycle. It is given through a small plastic tube that is put in an arm vein. They will take olaparib by mouth twice every day. They will keep a medicine diary. Participants will take the study drugs until their disease gets worse or they have unacceptable side effects. About 30 days after they stop taking the study drugs, participants will have a follow-up visit. Then they will be contacted every 6 months for the rest of their life....
Detailed description
Background: Targeted therapies designed for specific genetic alterations, known as cancer driver mutations, have changed the treatment paradigm in advanced non-small cell lung carcinoma (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective in NSCLC with activating mutation in the EGFR. Although most patients achieve robust responses to EGFR tyrosine kinase inhibitors (TKIs) with tumor shrinkage and symptomatic relief, drug resistance eventually develops in the majority of patients. Small cell lung cancer (SCLC) transformation has been reported as one of the mechanisms of acquired resistance to EGFR TKIs. Several phase III trials showed durable response with poly adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors in the breast and ovarian cancer with breast cancer gene (BRCA) mutation, a tumor suppressor gene involving homologous recombination repair (HRR) pathway, and several PARP inhibitors are now Food and Drug Administration (FDA) approved for these cancers. Immune checkpoint blockade appears to be most effective against hypermutated tumors, suggesting that clinical responses correlate with an increased propensity to produce neoantigens. EGFR-mutated transformed SCLC is an aggressive cancer whose clinical course is similar to that of SCLC. There are no standard treatments for this disease and prospective studies have not been conducted to date. Immune checkpoint inhibitors alone are not effective for EGFR-mutated transformed SCLC. Analyses of EGFR transformed SCLC tumors suggest that these tumors are HRR deficient. Objective: To assess the efficacy of a combination of durvalumab and olaparib with respect to best overall response (BOR) according to Response Evaluation Criteria (RECIST 1.1) in patients with EGFR-mutated non-small-cell lung carcinoma (NSCLC) that transform to SCLC and other neuroendocrine carcinomas. Eligibility: Subjects with initial diagnosis of EGFR-mutated non-small-cell lung carcinoma (NSCLC) and histologically or cytologically confirmed transformation to small cell/neuroendocrine tumors following treatment with EGFR tyrosine kinase inhibitor. Subjects should have received platinum-based chemotherapy with or without immunotherapy for small cell/neuroendocrine transformation or refused such therapy. Age \>=18 years. Subjects must have measurable disease. Eastern Cooperative Oncology Group (ECOG) performance status \<= 2 Adequate organ function Design: -This is an open label Phase II study evaluating the combination of durvalumab and olaparib in participants with EGFR-mutated non-small-cell lung carcinoma and histologically or cytologically confirmed transformation to small cell/neuroendocrine tumors following treatment with EGFR tyrosine kinase inhibitor. Patients will be treated with durvalumab (1,500 mg), intravenous (IV), every 28 days and olaparib (300 mg twice a day (BID) for total daily dose of 600 mg) in a 28-day cycles. Patients will be evaluated for toxicity every 4 weeks by Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and for response every 8 (+/-1) weeks by RECIST 1.1 Treatment will continue until disease progression or unacceptable toxicity.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Olaparib | Olaparib tablet will be administered at a total daily dose of 600 mg orally in two divided doses, approximately 12 hours apart. |
| DRUG | Durvalumab | Durvalumab will be administered intravenous (IV) into a peripheral or central vein on Day 1 of every cycle at a flat dose of 1,500 mg. |
| DIAGNOSTIC_TEST | EKG | Screening and all cycles Day 1 and Day 15 (+/- 3) days. One cycle is 28 days. |
| PROCEDURE | Tumor biopsy | Baseline and all cycles Day 15 (+/- 3) days. One cycle is 28 days. |
| DIAGNOSTIC_TEST | CT chest, abdomen and pelvis | Screening and baseline and every 8 (+/-1) weeks after start of therapy. |
| DIAGNOSTIC_TEST | MRI chest, abdomen and pelvis | Screening and baseline and every 8 (+/-1) weeks after start of therapy. |
Timeline
- Start date
- 2021-07-07
- Primary completion
- 2023-03-22
- Completion
- 2024-02-27
- First posted
- 2020-09-04
- Last updated
- 2025-01-27
- Results posted
- 2025-01-27
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04538378. Inclusion in this directory is not an endorsement.