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

Conditions:Breast Cancer, Lung Cancer, Lung Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:April 26, 2016

Use our guide to learn which trials are right for you!

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 or cannot be removed
by surgery, 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.


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).


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.


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


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 course 1.
Courses repeat every 28 days (35 days for course 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.

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 may be
considered after discussion with the study principal investigator (PI)

- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky >=

- 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

- 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, with no symptoms of thyroid dysfunction;
elevated thyroid stimulating hormone (TSH) with normal T3 and T4 are allowed; patients
on thyroid replacement therapy are allowed

- 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

- 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

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

- 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

- 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

- 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

- 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

- 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
We found this trial at
San Diego, California 92093
Principal Investigator: Shumei Kato
Phone: 858-822-5354
San Diego, CA
Click here to add this to my saved trials
401 College Street
Richmond, Virginia 23298
(804) 828-0450
Principal Investigator: Sosipatros A. Boikos
Phone: 888-823-5923
Virginia Commonwealth University Massey Cancer Center Founded in 1974, VCU Massey Cancer Center is a...
Richmond, VA
Click here to add this to my saved trials
450 Brookline Ave
Boston, Massachusetts 2215
Principal Investigator: Geoffrey I. Shapiro
Phone: 877-442-3324
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
Boston, MA
Click here to add this to my saved trials
4160 John R St #2122
Detroit, Michigan 48201
(313) 833-1785
Principal Investigator: Ulka N. Vaishampayan
Phone: 313-576-9790
Wayne State University/Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
Detroit, MI
Click here to add this to my saved trials
Farmington Hills, Michigan 48334
Principal Investigator: Ulka N. Vaishampayan
Phone: 313-576-9790
Farmington Hills, MI
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Siqing Fu
Phone: 877-312-3961
Houston, TX
Click here to add this to my saved trials
3855 Health Sciences Dr,
La Jolla, California 92093
(858) 822-6100
Principal Investigator: Shumei Kato
Phone: 858-822-5354
UC San Diego Moores Cancer Center Established in 1978, UC San Diego Moores Cancer Center...
La Jolla, CA
Click here to add this to my saved trials
Nashville, Tennessee 37232
Principal Investigator: Dana B. Cardin
Phone: 800-811-8480
Nashville, TN
Click here to add this to my saved trials
New Haven, Connecticut 06510
Principal Investigator: Joseph W. Kim
Phone: 203-785-5702
New Haven, CT
Click here to add this to my saved trials
New Haven, Connecticut 6520
(203) 432-4771
Principal Investigator: Joseph W. Kim
Phone: 203-785-5702
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
New Haven, CT
Click here to add this to my saved trials
Sacramento, California 95817
Principal Investigator: Primo N. Lara
Phone: 916-734-3089
Sacramento, CA
Click here to add this to my saved trials
San Francisco, California 94115
Principal Investigator: Pamela N. Munster
Phone: 877-827-3222
San Francisco, CA
Click here to add this to my saved trials
Tampa, Florida 33612
Principal Investigator: Hatem H. Soliman
Phone: 800-456-7121
Tampa, FL
Click here to add this to my saved trials
Tampa, Florida 33067
Principal Investigator: Hatem H. Soliman
Tampa, FL
Click here to add this to my saved trials
Vancouver, British Columbia
Principal Investigator: Daniel J. Renouf
Phone: 888-939-3333
Click here to add this to my saved trials