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

NCT02498613 | Active Not Recruiting Phase 2 Results DMC

• 5 other identifiers: NCI-2015-0109716040175769881UM1CA186644UM1CA186689
• Study Type: interventional
• Target: 122
• Locations: 2 countries
• Sites: 16

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.

Conditions

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; Advanced Malignant Solid Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 4 weeks after completion of study treatment (Up to 43 months)

Secondary Outcomes (2)

• Incidence of Adverse Events

  Up to 4 weeks after completion of study treatment (Up to 44 months)

• Progression-free Survival

  Up to 4 weeks after completion of study treatment (Up to 44 months)

Other Outcomes (4)

• Prevalence of the Mutations of Deoxyribonucleic Acid (DNA) Repair Genes in Each Tumor Cohort

  Up to 2 years

• Changes in Tumor Hypoxia by Imaging

  Baseline to post-cediranib monotherapy

• Changes in Level of Circulating Tumor Deoxyribonucleic Acid (ctDNA) (All Cohorts)

  Baseline to post therapy

Study Arms (1)

Treatment (cediranib maleate, olaparib)

EXPERIMENTAL

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.

Other: 18F-Fluoromisonidazole; Drug: Cediranib Maleate; Other: Laboratory Biomarker Analysis; Drug: Olaparib; Procedure: Positron Emission Tomography

Interventions

18F-Fluoromisonidazole OTHER

Correlative studies

Also known as: 18F-MISO, 18F-Misonidazole, FLUOROMISONIDAZOLE F-18, FMISO

Treatment (cediranib maleate, olaparib)

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Treatment (cediranib maleate, olaparib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (cediranib maleate, olaparib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Treatment (cediranib maleate, olaparib)

Positron Emission Tomography PROCEDURE

Correlative studies

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (cediranib maleate, olaparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• AstraZeneca: collaborator

Study Sites (16)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center-International Plaza

Tampa, Florida, 33607, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

fluoromisonidazole; cediranib; olaparib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Joseph Kim, MD
• Organization: Yale School of Medicine

joseph.w.kim@yale.edu

(203) 200-4822

Study Officials

• Joseph W Kim

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 15, 2015
• Study Start: August 31, 2016
• Primary Completion: June 22, 2022
• Study Completion (Estimated): April 10, 2027
• Last Updated: May 1, 2026
• Results First Posted: July 30, 2024

Record last verified: 2026-03

Locations

US (14); CA (2)