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

Primary Purpose

Advanced Malignant Solid Neoplasm, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
18F-Fluoromisonidazole
Cediranib Maleate
Laboratory Biomarker Analysis
Olaparib
Positron Emission Tomography
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Malignant Solid Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
    • History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded from the study)
  • The effects of cediranib and olaparib on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of cediranib and olaparib administration
  • Ability to understand and the willingness to sign a written informed consent document
  • Age >= 18 years. There is no dosing or adverse event data currently available on the use of cediranib or olaparib in patients < 18 years of age, thus excluding them from enrollment

Exclusion Criteria:

  • 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)
  • Patients may not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted; the clinical indication for therapeutic anticoagulation must be clearly documented prior to enrollment and must be discussed with the P.I.; given the increases risk of serious bleeding from cediranib, patients who are on greater than or equal to 2 anti-thrombotic agents, including but not limited to anti-platelet agents (non-steroidal anti-inflammatory drugs [NSAIDs]/aspirin, clopidogrel), heparin, low molecular weight heparin (LMWH), warfarin, and a direct thrombin inhibitor, will be excluded
  • Patients may not have features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated
  • Pregnant women are excluded from this study because olaparib and cediranib have the potential for teratogenic or abortifacient effects; due to the fact that there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib and cediranib, breastfeeding should be discontinued if the mother is treated with cediranib and olaparib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated; HIV-positive patients with undetectable viral loads and CD4 counts > 300, and not on any antiretroviral therapy may be allowed after discussing with the principle investigator
  • Any condition that, in the opinion of the treating investigator would interfere with evaluation of the investigational product or interpretation of subject safety or study results

Sites / Locations

  • UC San Diego Moores Cancer Center
  • University of California Davis Comprehensive Cancer Center
  • UC San Diego Medical Center - Hillcrest
  • UCSF Medical Center-Mount Zion
  • Smilow Cancer Center/Yale-New Haven Hospital
  • Yale University
  • Moffitt Cancer Center-International Plaza
  • Moffitt Cancer Center
  • Dana-Farber Cancer Institute
  • Wayne State University/Karmanos Cancer Institute
  • Weisberg Cancer Treatment Center
  • Vanderbilt University/Ingram Cancer Center
  • M D Anderson Cancer Center
  • Virginia Commonwealth University/Massey Cancer Center
  • BCCA-Vancouver Cancer Centre
  • University Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (cediranib maleate, olaparib)

Arm Description

Patients receive cediranib maleate PO QD on day 1. Patients undergoing FMISO scan also receive olaparib PO BID beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Objective response rate
Measured by Response Evaluation Criteria in Solid Tumors version 1.1. The exact two-sided 95% confidence interval for the objective response rate will be reported.

Secondary Outcome Measures

Incidence of adverse events
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percentages and frequencies for categorical parameters, will be presented. Adverse medical events will be tabulated. National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
Progression-free survival
Estimated using the Kaplan-Meier method with the 95% confidence intervals. Thomas and Grunkemeier confidence interval will be reported. The possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.

Full Information

First Posted
July 14, 2015
Last Updated
September 23, 2023
Sponsor
National Cancer Institute (NCI)
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02498613
Brief Title
A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors
Official Title
A Phase 2 Study of Cediranib in Combination With Olaparib in Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 31, 2016 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine the objective response rate (ORR) of cediranib (cediranib maleate) plus olaparib in combination in patients with advanced or metastatic solid tumors of the following tumor types: non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumors. II. To estimate progression free survival (PFS) in each tumor cohort. EXPLORATORY OBJECTIVES: I. To estimate the prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in tumors using the BROCA panel and to correlate tumor regression with mutations status. (Integrated) II. To evaluate changes in tumor hypoxia on cediranib treatment compared to baseline by [F-18] fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET/CT) in patients with NSCLC. III. To evaluate levels of angiogenesis/inflammatory markers including VEGF at baseline and on treatment. IV. To evaluate levels of circulating tumor deoxyribonucleic acid (ctDNA) at baseline and on treatment. OUTLINE: Patients receive cediranib maleate orally (PO) once daily (QD) on day 1. Patients undergoing FMISO scan also receive olaparib PO twice daily (BID) beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 4 weeks thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
126 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (cediranib maleate, olaparib)
Arm Type
Experimental
Arm Description
Patients receive cediranib maleate PO QD on day 1. Patients undergoing FMISO scan also receive olaparib PO BID beginning the day after the second FMISO scan and the rest of the patients receive olaparib PO BID beginning day 4 of cycle 1. Cycles repeat every 28 days (35 days for cycle 1) in the absence of disease progression or unacceptable toxicity.
Intervention Type
Other
Intervention Name(s)
18F-Fluoromisonidazole
Other Intervention Name(s)
18F-MISO, 18F-Misonidazole, FLUOROMISONIDAZOLE F-18, FMISO
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Cediranib Maleate
Other Intervention Name(s)
AZD2171, AZD2171 Maleate, Recentin
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Positron Emission Tomography
Other Intervention Name(s)
Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective response rate
Description
Measured by Response Evaluation Criteria in Solid Tumors version 1.1. The exact two-sided 95% confidence interval for the objective response rate will be reported.
Time Frame
Up to 4 weeks after completion of study treatment
Secondary Outcome Measure Information:
Title
Incidence of adverse events
Description
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics, including means, standard deviations, and ranges for continuous parameters, as well as percentages and frequencies for categorical parameters, will be presented. Adverse medical events will be tabulated. National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
Time Frame
Up to 4 weeks after completion of study treatment
Title
Progression-free survival
Description
Estimated using the Kaplan-Meier method with the 95% confidence intervals. Thomas and Grunkemeier confidence interval will be reported. The possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the hazard ratios and the adjusted 95% confidence interval will be reported.
Time Frame
The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after completion of study treatment
Other Pre-specified Outcome Measures:
Title
Prevalence of the mutations of deoxyribonucleic acid (DNA) repair genes in each tumor cohort
Description
In the first 20 endpoint-evaluable patients with non-small cell lung cancer and 20 endpoint-evaluable patients with triple negative breast cancer, the exploratory analyses will be done using Fisher's exact tests, Mann-Whitney U tests or McNemar's test depending on the type of data observed.
Time Frame
Up to 2 years
Title
Changes in tumor hypoxia by imaging
Description
Measured by 18F-fluoromisonidazole positron emission tomography/computed tomography scans (non-small cell lung cancer). For the pre- and post-cediranib therapy outcome analysis, paired t- test or Wilcoxon signed-rank test will be applied for the continuous variables.
Time Frame
Baseline to post-cediranib monotherapy
Title
Changes in level of circulating tumor deoxyribonucleic acid (ctDNA) (all cohorts)
Description
Will be assessed using paired t- test or Wilcoxon signed-rank.
Time Frame
Baseline to post therapy
Title
Changes in levels of angiogenesis/ inflammatory markers (angiome panel) (all cohorts)
Description
Will be assessed using paired t- test or Wilcoxon signed-rank.
Time Frame
Baseline to post-therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded from the study) The effects of cediranib and olaparib on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; 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; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 4 months after completion of cediranib and olaparib administration Ability to understand and the willingness to sign a written informed consent document Age >= 18 years. There is no dosing or adverse event data currently available on the use of cediranib or olaparib in patients < 18 years of age, thus excluding them from enrollment Exclusion Criteria: 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) Patients may not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted; the clinical indication for therapeutic anticoagulation must be clearly documented prior to enrollment and must be discussed with the P.I.; given the increases risk of serious bleeding from cediranib, patients who are on greater than or equal to 2 anti-thrombotic agents, including but not limited to anti-platelet agents (non-steroidal anti-inflammatory drugs [NSAIDs]/aspirin, clopidogrel), heparin, low molecular weight heparin (LMWH), warfarin, and a direct thrombin inhibitor, will be excluded Patients may not have features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated Pregnant women are excluded from this study because olaparib and cediranib have the potential for teratogenic or abortifacient effects; due to the fact that there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib and cediranib, breastfeeding should be discontinued if the mother is treated with cediranib and olaparib Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated; HIV-positive patients with undetectable viral loads and CD4 counts > 300, and not on any antiretroviral therapy may be allowed after discussing with the principle investigator Any condition that, in the opinion of the treating investigator would interfere with evaluation of the investigational product or interpretation of subject safety or study results
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph W Kim
Organizational Affiliation
Yale University Cancer Center LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
UC San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC San Diego Medical Center - Hillcrest
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
UCSF Medical Center-Mount Zion
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Smilow Cancer Center/Yale-New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Moffitt Cancer Center-International Plaza
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Weisberg Cancer Treatment Center
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
BCCA-Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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