Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Ca

• Status: Recruiting
• Trial end date: 2022-12-29
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Durvalumab is a drug that may help people s immune systems respond to and kill cancer cells. Olaparib is a drug that may inhibit repairing DNA damage of cancer cells. Cediranib is a drug that may stop the blood vessel growth of cancer cells. This study has two components. In the phase 1 component of the study, researchers want to investigate how well participants tolerate the combination of these drugs in treating advanced solid tumors, and in the phase 2 part of this study, researchers want to study if the combination treatments are effective in ovarian cancer.

Objectives:

• Phase 2 part of the study: To determine how effective this combination is in treating ovarian cancer.

Eligibility:

• Phase 2 part of the study: Adults age 18 or older with advanced or recurrent ovarian cancer that has no standard treatment.

Design:

• Participants will be screened with medical history, physical exam, and blood and urine tests. They will have CT or MRI scans. For these, they will lie in a machine that takes pictures of their bodies.

• Phase 2 part of the study requests the participants to have tumor samples removed.

• Participants will get Durvalumab through an IV. A small plastic tube will be inserted into a vein. The drug will be given every 4 weeks until disease progression.

• Participants will take olaparib or cediranib by mouth every day.

• Every 28 days will be 1 cycle. For cycle 1, participants will have 2 study visits. All other cycles, they will have 1 visit. At these visits, they will repeat the screening procedures.

• Patients will keep a drug and diarrhea diary.

• Patients on cediranib will monitor their blood pressure and keep a blood pressure diary.

• Participants who can become pregnant, or have a partner who can become pregnant, must practice an effective form of birth control.

• After 12 cycles, participants will have 1-3 months of follow-up.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Antibodies; Antibodies, Monoclonal; Cediranib; Durvalumab; Olaparib

Criteria

• ELIGIBILITY:

INCLUSION CRITERIA GENERAL:

• Patients must be at least 18 years of age.

• Patients must have adequately controlled blood pressure on a maximum of three antihypertensive medications.

• Patients who have the following clinical conditions are considered to be at increased risk for cardiac toxicities.

Patients with any cardiac history of the following conditions within 1 year prior to study enrollment are excluded from the study:

• Prior events including myocardial infarction, pericardial effusion, and myocarditis.

• Prior cardiac arrhythmia including atrial fibrillation and atrial flutter, or requiring concurrent use of drugs or biologics with pro-arrhythmic potential.

• NYHA Class II or greater heart failure.

• If cardiac function assessment is clinically indicated or performed, an LVEF less than normal per institutional guidelines, or <55%, if threshold for normal is not otherwise specified by institutional guidelines.

• QTc prolongation >470 msec or other significant ECG abnormality noted within 14 days of treatment.

• Hypertensive crisis or hypertensive encephalopathy.

• Clinically significant peripheral vascular disease or vascular disease, including rapidly growing aortic aneurysm or abdominal aortic aneurysm >5 cm or aortic dissection.

• Unstable angina.

• Eligibility for patients with asymptomatic and a previous diagnosis of immune or inflammatory colitis, or patients with chronic diarrhea > 1 month without immune or inflammatory colitis is a PI decision on an individual patient basis.

• Patients with a history of cerebrovascular accident or transient ischemic attack within 1 year prior to study enrollment are not eligible.

• Patients with a history of previous clinical diagnosis of tuberculosis are not eligible.

• Patients with a history of auto-immune disease requiring steroid maintenance, or history of primary immunodeficiency are not eligible.

• HIV-positive patients on antiretroviral therapy are ineligible because of potential pharmacokinetic interactions with study drugs, however, patients with long-standing (>5 years) HIV on antiretroviral therapy > 1 month (undetectable HIV viral load and CD4 count > 150 cells/microL) may be eligible if the PI determines no anticipated clinically significant drug-drug interactions.

• HBV-or HCV-positive patients are ineligible because of potential reactivation of hepatitis virus following steroids.

• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEDI4736, olaparib, cediranib, or to other humanized monoclonal antibodies, or a history of anaphylaxis, angioedema, laryngeal edema, serum sickness, or uncontrolled asthma, are not eligible.

• Patients who have had prior immune checkpoint inhibitors, such as MEDI4736 or other PD1 or PD-L1 inhibitors or an anti-CTLA4 therapy are eligible.

• Pregnant and breastfeeding women are excluded from this study.

• Patients with any other concomitant or prior invasive malignancies are ineligible.

PHASE II MEDI4736 PLUS OLAPARIB OR CEDIRANIB STUDY ELIGIBILITY CRITERIA - OVARIAN CANCER

• Patients must have histologically or cytologically confirmed persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer and have received at least two prior regimens or who are platinum resistant or refractory during or after a first platinum containing regimen.

• Patients must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy.

• Patients are allowed to have received prior PARPi, and/or anti-angiogenesis therapy including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, or other anti-angiogenics. However, patients who were treated with both olaparib and cediranib, either in combination or sequentially are not eligible. For this study, BSI-201 (iniparib) is not considered as PARPi.

PHASE II STUDY MEDI4736 PLUS OLAPARIB ELIGIBILITY CRITERIA TRIPLE NEGATIVE BREAST CANCER

• Patients must have histologically confirmed persistent or recurrent triple-negative breast cancer (TNBC)

• ER/PR/HER2 status needs to be documented either by an outside source or at NCI.

• Documentation of germline BRCA1 and BRCA2 mutation (gBRCAm) status will be required for eligibility.

• Patients must have measurable disease as defined by RECIST v1.1.

• Patients must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy.

• Patients who have received prior PARPi are ineligible.

• Patients must not have evidence of CNS metastasis or leptomeningeal disease within one year prior to enrollment.

PHASE II MEDI4736 PLUS OLAPARIB OR CEDIRANIB STUDY ELIGIBILITY CRITERIA - NON-SMALL CELL LUNG CANCER

• Histologically or cytologically confirmed advanced NSCLC with at least one prior line of platinum-based chemotherapy (or treatment with EGFR, ALK, or BRAF-targeted tyrosine kinase inhibitors if tumors harbor an EGFR-sensitizing mutation, ALK translocation, or BRAF V600E mutation, respectively).

• Patients must have measurable disease as defined by RECIST v1.1.

• Patients must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy.

• Patients who have received anti-angiogenesis therapy are eligible, including but not limited to thalidomide, bevacizumab, sunitinib, sorafenib, or other anti-angiogenics. However, patients who were treated with cediranib, either in combination or monotherapy are not eligible.

• Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid.

• Patients who have had prior PARPi are not eligible.

• Patients with prior history of pneumonitis and/or interstitial lung disease will be excluded.

PHASE II MEDI4736 PLUS OLAPARIB STUDY ELIGIBILITY CRITERIA - METASTATIC CASTRATE-RESISTANT PROSTATE CANCER

• Patients must have metastatic, progressive, castrate resistant prostate cancer (mCRPC).

• All patients must have at least one lesion deemed safe to biopsy and be willing to undergo a mandatory baseline biopsy.

• Patients must have received prior treatment with enzalutamide and/or abiraterone with the exception of patients who were treated with docetaxel and androgen deprivation therapy for metastatic castrate-sensitive prostate cancer and progressed on docetaxel treatment or who progress within one month of the last docetaxel dose.

• Patients must have undergone bilateral surgical castration or must agree to continue on GnRH agonists/antagonists for the duration of the study.

• Patients who have had progression of prostate cancer on prior docetaxel treatment for castrate sensitive disease are ineligible.

• Patients who have had prior treatment with PARPi are not eligible.

• Patients who have received radionuclide treatment within 6 weeks prior to the first dose of the study treatment are not eligible.

• Patients with any other concomitant or prior invasive malignancies are ineligible.