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Clinical Trial 18844

Cancer Type: Multiple
Interventions:AZD2171 (Cediranib); Cediranib (Recentin); Olaparib (Lynparza)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Hatem Soliman

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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

Summary

The purpose of this study is to test any good and bad effects of this combination of drugs - cediranib and olaparib. Researchers hope to learn if this combination of the drugs will shrink the cancer by at least one-quarter compared to its present size. Cediranib is an experimental drug. Olaparib has already been FDA-approved to treat patients with advanced ovarian cancer.

Objective

Primary Objectives To determine the objective response rate (ORR) of cediranib plus olaparib in combination in patients with advanced or metastatic solid tumors of the following tumor types: non-small cell lung cancer (NSCLC), germline BRCA1/2wt, basaloid triple negative breast cancer (b-TNBC), pancreatic ductal adenocarcinoma (PDAC), and small cell lung cancer (SCLC). The responses will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary Objectives To assess the safety and tolerability of oral administration of cediranib in combination with olaparib in patients with select advanced solid tumors.

Inclusion Criteria

  • 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 ER> 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: 5-FU-, gemcitabine-, or taxane-containing chemotherapy either with or without radiation therapy; SCLC: platinum-containing chemotherapy for limited or extensive stage disease.
  • Must have measurable disease by RECIST v1.1.
  • Toxicities of prior therapy (except alopecia) should be resolved to ≤ grade 1 as per NCI- CTCAE v5.0. 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).
  • Age 18 years or older. There is no dosing or adverse event data currently available on the use of cediranib or olaparib in patients > Must have normal organ and marrow function as defined per protocol.
  • 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) > Patients who have risk factors per protocol are considered to be at increased risk for cardiac toxicities, and must have documented 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.
  • 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 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 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 criteria per protocol.
  • Patients who have received prior inhibitor of VEGF signaling and a 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 CYP3A4 (See Appendix C) 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 (>5cm) or aortic dissection. If known history of abdominal aortic aneurysm with >4cm in diameter, all criteria per protocol must be met.
  • 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 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.
  • Additional criteria apply