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
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 4
- Locations
- 1
- Primary Endpoint
- Best Overall Response (BOR)
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
1/Arm 1: Combination of Durvalumab and Olaparib
Combination of durvalumab and olaparib
Intervention: Olaparib (Drug)
1/Arm 1: Combination of Durvalumab and Olaparib
Combination of durvalumab and olaparib
Intervention: Durvalumab (Drug)
1/Arm 1: Combination of Durvalumab and Olaparib
Combination of durvalumab and olaparib
Intervention: EKG (Diagnostic Test)
1/Arm 1: Combination of Durvalumab and Olaparib
Combination of durvalumab and olaparib
Intervention: Tumor biopsy (Procedure)
1/Arm 1: Combination of Durvalumab and Olaparib
Combination of durvalumab and olaparib
Intervention: CT chest, abdomen and pelvis (Diagnostic Test)
1/Arm 1: Combination of Durvalumab and Olaparib
Combination of durvalumab and olaparib
Intervention: MRI chest, abdomen and pelvis (Diagnostic Test)
Outcomes
Primary Outcomes
Best Overall Response (BOR)
Time Frame: Disease progression; an average of 53 days
BOR is the best response recorded from the start of the treatment until disease progression/recurrence. The clinical response rate of evaluable participants will be reported along with a 95% confidence interval according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Secondary Outcomes
- Progression-free Survival (PFS)(Disease progression, an average of 7 weeks)
- Number of Participants With Grades 1, 2, 3, 4 and/or 5 Serious and/or Non-serious Toxicity(Treatment phase, an average of 12 weeks)
- Overall Survival (OS)(At death, an average of 275 days)
Investigators
Anish Thomas
Principal Investigator
National Cancer Institute (NCI)