A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors

Running, not enrolling · Phase 2

Conditions studied: Advanced Malignant Solid Neoplasm, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma, Metastatic Pancreatic Adenocarcinoma, Metastatic Triple-Negative Breast Carcinoma, Pancreatic Ductal Adenocarcinoma, Stage III Breast Cancer AJCC v7, Stage III Lung Non-Small Cell Cancer AJCC v7, Stage III Lung Small Cell Carcinoma AJCC v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage IIIA Breast Cancer AJCC v7, Stage IIIA Lung Non-Small Cell Cancer AJCC v7, Stage IIIA Lung Small Cell Carcinoma AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage IIIB Lung Non-Small Cell Cancer AJCC v7, Stage IIIB Lung Small Cell Carcinoma AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Lung Non-Small Cell Cancer AJCC v7, Stage IV Lung Small Cell Carcinoma AJCC v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Triple-Negative Breast Carcinoma, Unresectable Lung Small Cell Carcinoma, Unresectable Pancreatic Adenocarcinoma, Unresectable Pancreatic Carcinoma, Unresectable Triple-Negative Breast Carcinoma

In brief

This phase II trial studies cediranib maleate in combination with olaparib in treating patients with solid tumors that have spread to other parts of the body (advanced/metastatic) or cannot be removed by surgery (unresectable), including breast cancer, non-small cell lung cancer, small cell lung cancer, and pancreatic cancer. Cediranib maleate and olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may also block the flow of oxygen to the tumor, and may help make the tumor more sensitive to olaparib.

Key facts

Study ID

NCT02498613

Run by

National Cancer Institute (NCI)

People needed

122

Starts

2016-08-31

Expected to finish

2027-04-10

Last updated by the study team

2026-06-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients must have histologically confirmed, metastatic or unresectable malignancy of the following types: (a) non-small cell lung cancer (NSCLC), (b) triple-negative breast cancer (TNBC; defined by estrogen receptor [ER] < 1%, progesterone receptor [PR] < 1% and HER2 1+ or less by immunohistochemistry [IHC]; if HER-2 expression is 2+, a negative fluorescence in situ hybridization [FISH] testing is required) (c) pancreatic adenocarcinoma (PDAC), or (d) small cell lung cancer (SCLC)
• Must have received at least one line of standard systemic treatment for locally advanced or metastatic disease setting of the respective tumor type; for NSCLC, it is either PD-1/PD-L1 inhibitor, or platinum-containing chemotherapy, or an EGFR tyrosine kinase inhibitor or an ALK inhibitor if sensitizing mutation present; TNBC: platinum-containing chemotherapy; PDAC: fluorouracil (5-FU-), gemcitabine-, or taxane-containing chemotherapy either with or without radiation therapy; SCLC: platinum-containing chemotherapy for limited or extensive stage disease
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Toxicities of prior therapy (except alopecia) should be resolved to =< grade 1 as per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0; patients with long-standing stable grade 2 neuropathy or prior grade 2 treatment-related hypothyroidism requiring treatment, provided free T4 within normal range, may be considered eligible after discussion with the study principal investigator (PI)
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky >= 50%)
• Life expectancy of >= 4 months
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin > 9 g/dL
• Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
• Creatinine =< 1.5 x ULN OR
• Creatinine clearance >= 45 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal; the creatinine clearance is calculated using Cockcroft-Gault formula
• A urine protein: creatinine ratio of < 1 or < 1 g protein on 24-hour urine collection
• International normalized ration (INR) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
• Activated partial thromboplastin time (aPTT) within 1.25 x ULN institutional limits, except where a lupus anti-coagulant has been confirmed
• Patients must be able to tolerate oral medications and not have gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
• Adequately controlled thyroid function defined by free T4 within normal range, with no symptoms of thyroid dysfunction
• Adequately controlled blood pressure (BP) < 140 mmHg (systolic) and < 90 mmHg (diastolic) taken in the clinic setting by a medical professional within 2 weeks prior to starting study; patients with hypertension may be managed with up to a maximum of 3 antihypertensive medications; patients who are on 3 antihypertensive medications are highly recommended to be followed by a cardiologist or blood pressure specialist for management of BP while on protocol
• Patients who have the following risk factors are considered to be at increased risk for cardiac toxicities, and must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution's lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 3 months
• Prior treatment with anthracyclines
• Prior treatment with trastuzumab
• A New York Heart Association (NYHA) classification of II controlled with treatment
• Prior central thoracic radiation therapy (RT), including RT to the heart

You may not qualify if…

• Patients who have had chemotherapy or RT within 3 weeks prior to start of the study agents, or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
• Patients should not have received any other investigational agents within the past 4 weeks
• Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans should be excluded from this clinical trial, since neurologic dysfunction may confound the evaluation of neurologic and other adverse events (AEs); screening brain MRI (or CT if MRI contraindicated) will be required for patients with recurrent NSCLC, TNBC, or SCLC; brain MRI (or CT if MRI contraindicated) is required for PDAC if clinically suspected by patient's symptoms or neurological exam; should patient found to have brain metastasis, treatment of brain metastasis must precede the participation in this study; for patients with known and treated brain metastases is allowed in this study if they fulfill the following criteria:
• The lesions have improved or remained stable radiographically and clinically for at least 6 weeks after completion of brain irradiation or stereotactic brain radiosurgery and off steroids for at least 6 weeks
• Patients who have received prior inhibitor of VEGF signaling and a poly (ADP-ribose) polymerases (PARP) inhibitor administered in combination; unless administered in combination, patients who received a prior PARP inhibitor or a prior VEGF-signaling inhibitor agent are allowed after discussing with the PI
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or olaparib
• Participants receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; dihydropyridine calcium-channel blockers are permitted for management of hypertension
• Current use of natural herbal products or other complementary alternative medications (CAM) or "folk remedies"
• Patients with concomitant or prior invasive malignancies within the past 3 years; subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of myocardial infarction within 6 months prior to registration
• History of stroke or transient ischemic attack within 6 months prior to registration
• NYHA classification of III or IV
• Current cardiac arrhythmia requiring concurrent use of anti-arrhythmic drugs
• History of hypertensive crisis or hypertensive encephalopathy within 3 years prior to registration
• Clinically significant peripheral vascular disease or abdominal aortic aneurysm (> 5 cm) or aortic dissection; if known history of abdominal aortic aneurysm with >= 4 cm in diameter, all of the following must be met:
• An ultrasound (US) within the last 6 months prior to registration will be required to document that it is =< 5 cm
• Patient must be asymptomatic from the aneurysm
• Blood pressure must be well controlled as defined in this protocol
• A major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting cediranib (percutaneous/endobronchial biopsies are allowed)
• History of bowel obstruction within 1 month prior to starting study drugs
• History of hemoptysis or any significant bleeding within the last 1 month prior to enrollment
• Presence of cavitation of central pulmonary lesion
• History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the 3 months prior to enrollment
• Patients may not have current dependency on intravenous (IV) hydration or total parenteral nutrition (TPN)

Where it is running

• UC San Diego Moores Cancer Center — La Jolla, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• UC San Diego Medical Center - Hillcrest — San Diego, California, United States
• UCSF Medical Center-Mount Zion — San Francisco, California, United States
• Smilow Cancer Center/Yale-New Haven Hospital — New Haven, Connecticut, United States
• Yale University — New Haven, Connecticut, United States
• Moffitt Cancer Center-International Plaza — Tampa, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
• Weisberg Cancer Treatment Center — Farmington Hills, Michigan, United States
• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States
• UT MD Anderson Cancer Center — Houston, Texas, United States
• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States
• BCCA-Vancouver Cancer Centre — Vancouver, British Columbia, Canada
• University Health Network-Princess Margaret Hospital — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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