Study Stopped
Inadequate accrual rate
Olaparib, Cediranib Maleate, and Standard Chemotherapy in Treating Patients With Small Cell Lung Cancer
A Phase II Study of Olaparib Plus Cediranib in Combination With Standard Therapy for Small Cell Lung Cancer
5 other identifiers
interventional
9
1 country
24
Brief Summary
This phase II trial studies how well olaparib, cediranib maleate, and standard chemotherapy work in treating patients with small cell lung cancer. Drugs used in chemotherapy, such as carboplatin, cisplatin, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Olaparib, cediranib maleate, and standard chemotherapy may work better in treating patients with small cell lung cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2018
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 13, 2016
CompletedFirst Posted
Study publicly available on registry
September 14, 2016
CompletedStudy Start
First participant enrolled
March 30, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 17, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 17, 2020
CompletedResults Posted
Study results publicly available
April 19, 2021
CompletedOctober 17, 2023
September 1, 2023
2 years
September 13, 2016
March 22, 2021
September 22, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Median Progression-free Survival in Patients Who Receive Cediranib Maleate/Olaparib as Maintenance Therapy
Will be compared to those receiving standard therapy. will use the intention-to-treat framework in which all patients randomized are considered recipients of their randomized assignment, regardless of treatment actually received.
From second randomization to documented disease progression or death from any cause, whichever occurs first, assessed up to 6 months
Secondary Outcomes (3)
Overall Survival (OS) Rate
From initial randomization to death from any cause, assessed up to 2 years
Incidence of Adverse Events
Up to 2 years
Response Rate
Up to 2 years
Other Outcomes (3)
Blood-based Angiogenic and Deoxyribonucleic Acid (DNA) Repair Biomarkers
Up to 2 years
Frequency of Genomic Aberrations
Baseline up to 2 years
Change in Circulating Free DNA
Baseline up to 2 years
Study Arms (2)
Arm I (chemotherapy, cediranib maleate, olaparib)
EXPERIMENTALPatients receive carboplatin IV over 60 minutes or cisplatin IV over 60 minutes on day 1 and etoposide IV over 60 minutes on days 1, 2, and 3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients in Arm I who have stable disease, partial, or a complete response are randomized to receive maintenance therapy or no maintenance therapy. Patients in Arm II are assigned to receive maintenance therapy. MAINTENANCE THERAPY: Patients receive cediranib maleate PO QD and olaparib PO BID on days 1-28. NO MAINTENANCE THERAPY: Patients are eligible to crossover to receive treatment with cediranib maleate and olaparib upon disease progression at the treating investigator's discretion.
Arm II (chemotherapy, cediranib maleate, olaparib)
EXPERIMENTALPatients receive treatment as in Arm I and also receive cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive cediranib maleate PO QD and olaparib PO BID on days 1-28.
Interventions
Given IV
Given PO
Given PO
Given IV
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed diagnosis of extensive-stage small cell lung cancer with no prior systemic treatment
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional techniques or as \>= 10 mm (\>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- White blood cell count (WBC) \>= 3 x 10\^9/L (within 28 days prior to administration of therapy)
- No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear (within 28 days prior to administration of therapy)
- Absolute neutrophil count \>= 1,500/mcL (within 28 days prior to administration of therapy)
- Platelets \>= 100,000/mcL (within 28 days prior to administration of therapy)
- Hemoglobin \>= 10 g/dL with no blood transfusion within 28 days of initiation of therapy (within 28 days prior to administration of therapy)
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of therapy)
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x institutional ULN, unless liver metastases are present and then =\< 5 x institutional ULN is acceptable (within 28 days prior to administration of therapy)
- Creatinine clearance \>= 50 mL/min (within 28 days prior to administration of therapy)
- Proteinuria - urine protein:creatinine ratio (UPC) of =\< 1 OR =\< 2+ proteinuria on two consecutive urinalysis/dipstick tests taken no less than 1 week apart; patients with 2+ proteinuria on dipstick must also have a UPC of =\< 0.5 on 2 consecutive samples (within 28 days prior to administration of therapy)
- Ability to swallow and retain oral medication
- The effects of olaparib and cediranib on the developing human fetus are unknown; for this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and male patients and their partners who are sexually active must agree to use two highly effective forms of contraception in combination for the duration of study participation and for 3 months after completion of olaparib and cediranib administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Postmenopausal or evidence of non-pregnant status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to the start of therapy; postmenopausal status is defined as:
- +11 more criteria
You may not qualify if:
- Patients who have had major surgery or trauma within 28 days prior to entering the study; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
- Patients who have had radiotherapy within 14 days prior to entering the study
- Patients with a non-healing wound, fracture, or ulcer
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Common Terminology Criteria for Adverse Events \[CTCAE\] grade 1 or baseline, with the exception of alopecia)
- Patients who are receiving any other investigational agents
- Patients with symptomatic central nervous system (CNS) metastases or leptomeningeal carcinomatosis should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; exceptions include patients with previously-treated CNS metastases or those with are asymptomatic, subcentimeter metastases, and have no requirement for steroids or anti-seizure medication for at least one week prior to study entry; screening with CNS imaging studies (CT scan or MRI) is required
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib, cediranib, carboplatin, cisplatin, or etoposide
- Patients with a history of myelodysplastic syndrome (MDS)
- Patients with a history of acute myeloid leukemia (AML), or patients with a history of any other primary malignancy within 3 years prior to initiation of treatment on this study; exceptions include: patients with a history of malignancies (other than AML) that were treated curatively and have not recurred within 3 years prior to study entry; resected basal and squamous cell carcinomas of the skin; and completely resected carcinoma in situ of any type
- Patients with clinically significant gastrointestinal abnormalities including, but not limited to:
- Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment
- History of intra-abdominal abscess within 3 months prior to starting treatment
- History of gastrointestinal (GI) perforation within 6 months prior to starting treatment
- Evidence of abdominal fistula within 6 months prior to starting treatment; history of abdominal fistula will be considered eligible if the fistula was surgically repaired, and there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula
- Patients with a history of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or insufficiently treated deep venous thrombosis (DVT) within the past 3 months; Note: Participants with recent DVT who have been treated with therapeutic anti-coagulants for at least 6 weeks are eligible, with the exception of participants being treated with warfarin, which is prohibited on this study; other oral anti-coagulants may be allowed after discussion with overall principal investigator (PI), but short half-life low molecular weight heparins are strongly preferred
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Los Angeles County-USC Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Keck Medical Center of USC Pasadena
Pasadena, California, 91105, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jacob Sands, MD
- Organization
- Dana- Farber Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Jacob Sands
Dana-Farber - Harvard Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 13, 2016
First Posted
September 14, 2016
Study Start
March 30, 2018
Primary Completion
March 17, 2020
Study Completion
March 17, 2020
Last Updated
October 17, 2023
Results First Posted
April 19, 2021
Record last verified: 2023-09