This study is NOT currently recruiting participants.
Number
20-C-0149
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Neonates;Pregnant Women;Children
Keywords
Targeted Therapy; (PARP) Inhibitors; Poly (ADP-ribose) Polymerase; Monoclonal Antibody
Recruitment Keyword(s)
None
Condition(s)
EGFR-Mutated Non-Small-Cell Lung Carcinoma; Small Cell/Neuroendocrine
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Drug: Olaparib Drug: Durvalumab Diagnostic Test: EKG Procedure/Surgery: Tumor biopsy Diagnostic Test: CT chest, abdomen and pelvis Diagnostic Test: MRI chest, abdomen and pelvis
Supporting Site
National Cancer Institute
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.
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INCLUSION CRITERIA: -Subjects with initial diagnosis of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung carcinoma (NSCLC) and histologically or cytologically confirmed transformation to small cell or neuroendocrine tumor 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 greater than or equal to 18 years. -Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. -Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2. -Adequate hematological function within 28 days prior to enrollment as defined below: --white blood cell (WBC) count greater than or equal to 3(SqrRoot) 10^9/L, --absolute neutrophil count (ANC) greater than or equal to 1.0(SqrRoot) 10^9/L, --platelet count greater than or equal to 75(SqrRoot) 10^9/L, and --Hemoglobin (Hgb) greater than or equal to 9 g/ dL if no blood transfusion within 4 weeks prior to enrollment OR >10 g/dL if no blood transfusion within 2 weeks prior to enrollment. -Adequate hepatic function within 28 days prior to enrollment as defined by: --a total bilirubin level less than or equal to 1.5 (SqrRoot) upper limit of normal (ULN); for subjects with documented/suspected Gilbert s disease, bilirubin less than or equal to 3 (SqrRoot) ULN --an aspartate aminotransferase (AST) level less than or equal to 2.5(SqrRoot) ULN, (less than or equal to 5X ULN if liver metastasis) --an alanine aminotransferase (ALT) level less than or equal to 2.5 (SqrRoot) ULN, (less than or equal to 5X ULN if liver metastasis). -Adequate renal function within 28 days prior to enrollment as defined by: --Creatinine OR Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl) ---< 1.5x institution upper limit of normal OR -- greater than or equal to 51 mL/min/1.73 m^2 for participant with creatinine levels -- greater than or equal to 1.5 X institutional ULN<TAB> Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard. -The effects of the study treatment on the developing human fetus are unknown; thus, individuals of childbearing potential (IOCBP) must agree to use 1 highly effective form of contraception and their partners must use a male condom, or they must totally/truly abstain from any form of sexual intercourse from the time of screening throughout the total duration of the protocol treatment and for at least 6 months after the last dose of the study drugs. Individuals that can father children and their partners must use a highly effective form of contraception from the time of screening throughout the total duration of the protocol treatment and for 3 months after the last dose of study treatment. -Should an individual become pregnant or suspect pregnancy while in this study, the treating physician should be notified immediately ---Postmenopausal or evidence of non-childbearing status for IOCBP: negative urine or serum pregnancy test within 28 days of enrollment and confirmed prior to treatment on day 1. Postmenopausal is defined as: amenorrheic for 1 year (12 months in a row) or more following cessation of exogenous hormonal treatments; luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for individuals under 50, radiation-induced oophorectomy with last menses >1 year ago; chemotherapy-induced menopause with more than one-year interval since last menses; surgical sterilization for IOCBP (bilateral oophorectomy or hysterectomy) or their partners. -Patients with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, patients who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for 2 weeks may be enrolled. Imaging to rule out brain metastases is not required for screening but should be performed prior to study enrollment if clinically indicated. -Subjects must be able to understand and willing to sign a written informed consent document EXCLUSION CRITERIA: -Patients who are receiving any other investigational agents. Patients may be on other clinical trials or treatment during screening to determine eligibility -Systemic anti-cancer treatment or major surgery within 2 weeks prior to enrollment. -Palliative radiation within 24 hours prior to enrollment. -High-dose consolidative chest radiation within 2 weeks prior to enrollment. -Major surgical procedure (as defined by the Investigator) within 28 days prior to enrollment. Note: local surgery of isolated lesions for palliative intent is acceptable. -Patients receiving any medications or substances that are moderate and strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4). Note: dihydropyridine calcium - channel blockers are permitted for management of underling disease. -History of auto-immune disease requiring steroid maintenance, or history of primary immunodeficiency. -Current or prior use of immunosuppressive medication within 14 days before the enrollment, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid. In the case of short-term use of systemic corticosteroids (less than 24 hours within 28 days) of greater than 10 mg/day of prednisone or an equivalent corticosteroid, the required washout period prior to enrollment is 7 days. -Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline clinical features suggestive of myelodysplastic syndrome or acute myelogenous leukemia. -Persistent toxicities (greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 2) with the exception of alopecia, caused by previous cancer therapy. -History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib or durvalumab. -Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Q wave and the T wave (QT) corrected for heart rate by Fridericia's cube root formula (QTcF) prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome. -Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing), hepatitis B (known positive hepatitis B virus (HBV) hepatitis B surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) and patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HBV or HCV ribonucleic acid (RNA). -Human immunodeficiency virus (HIV)-positive patients on antiretroviral therapy are ineligible because of potential pharmacokinetic interactions with study drugs. However, patients with long-standing (>5 years) HIV on antiretroviral therapy > 1 month (undetectable HIV viral load and cluster of differentiation 4 (CD4) count > 150 cells/microliters) may be eligible if the PI determines no anticipated clinically significant drug-drug interactions. -History of allogenic organ transplantation, bone marrow transplant or double umbilical cord blood transplantation (dUCBT). -Uncontrolled intercurrent illness or medical condition including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring medications ((except chronic atrial fibrillation/flutter with controlled vascular rate), or psychiatric illness/social situations that may impair the patients tolerance of study treatments and, in the judgment of the investigator, would make the patient inappropriate for the study. -Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication based on primary investigator decision. -Pregnant individuals are excluded from this study because olaparib is a poly adenosine diphosphate ribose polymerase (PARP) inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment with durvalumab and olaparib, nursing should be discontinued.
-Subjects with initial diagnosis of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung carcinoma (NSCLC) and histologically or cytologically confirmed transformation to small cell or neuroendocrine tumor 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 greater than or equal to 18 years.
-Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
-Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
-Adequate hematological function within 28 days prior to enrollment as defined below:
--white blood cell (WBC) count greater than or equal to 3(SqrRoot) 10^9/L,
--absolute neutrophil count (ANC) greater than or equal to 1.0(SqrRoot) 10^9/L,
--platelet count greater than or equal to 75(SqrRoot) 10^9/L, and
--Hemoglobin (Hgb) greater than or equal to 9 g/ dL if no blood transfusion within 4 weeks prior to enrollment OR >10 g/dL if no blood transfusion within 2 weeks prior to enrollment.
-Adequate hepatic function within 28 days prior to enrollment as defined by:
--a total bilirubin level less than or equal to 1.5 (SqrRoot) upper limit of normal (ULN); for subjects with documented/suspected Gilbert s disease, bilirubin less than or equal to 3 (SqrRoot) ULN
--an aspartate aminotransferase (AST) level less than or equal to 2.5(SqrRoot) ULN, (less than or equal to 5X ULN if liver metastasis)
--an alanine aminotransferase (ALT) level less than or equal to 2.5 (SqrRoot) ULN, (less than or equal to 5X ULN if liver metastasis).
-Adequate renal function within 28 days prior to enrollment as defined by:
--Creatinine OR Measured or calculated creatinine clearance (CrCl) (estimated glomerular filtration rate (eGFR) may also be used in place of CrCl)
---< 1.5x institution upper limit of normal OR
-- greater than or equal to 51 mL/min/1.73 m^2 for participant with creatinine levels
-- greater than or equal to 1.5 X institutional ULN<TAB>
Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.
-The effects of the study treatment on the developing human fetus are unknown; thus, individuals of childbearing potential (IOCBP) must agree to use 1 highly effective form of contraception and their partners must use a male condom, or they must totally/truly abstain from any form of sexual intercourse from the time of screening throughout the total duration of the protocol treatment and for at least 6 months after the last dose of the study drugs. Individuals that can father children and their partners must use a highly effective form of contraception from the time
of screening throughout the total duration of the protocol treatment and for 3 months after the last dose of study treatment.
-Should an individual become pregnant or suspect pregnancy while in this study, the treating physician should be notified immediately
---Postmenopausal or evidence of non-childbearing status for IOCBP: negative urine or serum pregnancy test within 28 days of enrollment and confirmed prior to treatment on day 1. Postmenopausal is defined as: amenorrheic for 1 year (12 months in a row) or more following cessation of exogenous hormonal treatments; luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for individuals under 50, radiation-induced oophorectomy with last menses >1 year ago; chemotherapy-induced menopause with more than one-year interval since last menses; surgical sterilization for IOCBP (bilateral oophorectomy or hysterectomy) or their partners.
-Patients with symptomatic brain metastases will be excluded from trial secondary to poor prognosis. However, patients who have had treatment for their brain metastasis and whose brain disease is stable without steroid therapy for 2 weeks may be enrolled. Imaging to rule out brain metastases is not required for screening but should be performed prior to study enrollment if clinically indicated.
-Subjects must be able to understand and willing to sign a written informed consent document
EXCLUSION CRITERIA:
-Patients who are receiving any other investigational agents. Patients may be on other clinical trials or treatment during screening to determine eligibility
-Systemic anti-cancer treatment or major surgery within 2 weeks prior to enrollment.
-Palliative radiation within 24 hours prior to enrollment.
-High-dose consolidative chest radiation within 2 weeks prior to enrollment.
-Major surgical procedure (as defined by the Investigator) within 28 days prior to enrollment. Note: local surgery of isolated lesions for palliative intent is acceptable.
-Patients receiving any medications or substances that are moderate and strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4).
Note: dihydropyridine calcium - channel blockers are permitted for management of underling disease.
-History of auto-immune disease requiring steroid maintenance, or history of primary immunodeficiency.
-Current or prior use of immunosuppressive medication within 14 days before the enrollment, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid. In the case of short-term use of systemic corticosteroids (less than 24 hours within 28 days) of greater than 10 mg/day of prednisone or an equivalent corticosteroid, the required washout period prior to enrollment is 7 days.
-Patients with myelodysplastic syndrome/acute myeloid leukemia; or baseline clinical features suggestive of myelodysplastic syndrome or acute myelogenous leukemia.
-Persistent toxicities (greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 2) with the exception of alopecia, caused by previous cancer therapy.
-History of allergic reactions attributed to compounds of similar chemical or biologic composition of olaparib or durvalumab.
-Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Q wave and the T wave (QT) corrected for heart rate by Fridericia's cube root formula (QTcF) prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
-Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis (TB) testing), hepatitis B (known positive hepatitis B virus (HBV) hepatitis B surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) and patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HBV or HCV ribonucleic acid (RNA).
-Human immunodeficiency virus (HIV)-positive patients on antiretroviral therapy are ineligible because of potential pharmacokinetic interactions with study drugs. However, patients with long-standing (>5 years) HIV on antiretroviral therapy > 1 month (undetectable HIV viral load and cluster of differentiation 4 (CD4) count > 150 cells/microliters) may be eligible if the PI determines no anticipated clinically significant drug-drug interactions.
-History of allogenic organ transplantation, bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
-Uncontrolled intercurrent illness or medical condition including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring medications ((except chronic atrial fibrillation/flutter with controlled vascular rate), or psychiatric illness/social situations that may impair the patients tolerance of study treatments and, in the judgment of the investigator, would make the patient inappropriate for the study.
-Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication based on primary investigator decision.
-Pregnant individuals are excluded from this study because olaparib is a poly adenosine diphosphate ribose polymerase (PARP) inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment with durvalumab and olaparib, nursing should be discontinued.
Principal Investigator
Referral Contact
For more information: