A Randomized Phase II Study Comparing Single-Agent Olaparib, Single Agent Cediranib, and the Combination of Cediranib/Olaparib in Women With Recurrent, Persistent or Metastatic Endometrial Cancer

J
Jeanne Schilder, MD

Primary Investigator

Overview

This phase II trial studies how well olaparib and cediranib maleate work in treating patients with endometrial cancer that has come back, does not respond to treatment, or has spread to other places in the body.

Description

Olaparib and cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    Endometrial Cancer, Uterine Corpus Cancer5
  • Age: Between 18 Years - 100 Years
  • Gender: Female

Inclusion Criteria
Patients must have recurrent or persistent endometrial carcinoma, which is refractory to curative therapy or established treatments; histologic confirmation of the original primary tumor is required; patients with the following histologic epithelial cell types are eligible: endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.); NOTE: clear cell histology is excluded
Patients must have evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or non-measurable (detectable) disease
Patients must have had one prior chemotherapeutic regimen for management of endometrial carcinoma; initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen
Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa; Note: patients on this non-cytotoxic study are allowed to receive one additional cytotoxic chemotherapy regimen for management of recurrent or persistent disease, as defined above; however, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy
Patients may have received non cytotoxic therapy including immunotherapy but excluding cediranib and olaparib for management of recurrent or persistent disease; prior hormonal therapy is allowed; hormonal therapy for grade 1 endometrial cancers with low volume or indolent disease is encouraged
The trial is open to females only (including women with an intact uterus with uterine cancer); fertile females of childbearing potential need to agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, and have a negative serum or urine pregnancy test within 3 days prior to the start of study treatment
Patients must be able to swallow and retain oral medications and without gastrointestinal illnesses that would preclude absorption of cediranib or olaparib
 Patients must have adequately controlled blood pressure (BP)
Patients must be willing and able to check and record daily blood pressure reading
Adequately controlled thyroid function, with no symptoms of thyroid dysfunction
Postmenopausal or evidence of non-childbearing status for women of childbearing potential as confirmed by a negative urine or serum pregnancy test within 7 days prior to start of investigational products (IPs); postmenopausal is defined as:
- Age >= 60 years, or - Age < 60 with any one or more of the conditions below:
- Amenorrheic for >= 1 year in the absence of chemotherapy and/or hormonal treatments,
- Luteinizing hormone and/or follicle stimulating hormone and/or estradiol levels in the post-menopausal range
- Radiation-induced oophorectomy with last menses > 1 year ago,
- Chemotherapy-induced menopause with > 1 year interval since last menses,
- Surgical sterilization (bilateral oophorectomy or hysterectomy)
Exclusion Criteria
Prior enrollment into a clinical trial including cediranib or olaparib; Note: prior bevacizumab is not an exclusion criterion - Prior chemotherapy, endocrine therapy, radiotherapy, or investigational agents within 4 weeks
Current signs/symptoms of bowel obstruction and/or signs/symptoms of bowel obstruction within the preceding 3 months
History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
 Uncontrolled intercurrent illness including, but not limited to known ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or psychiatric illness/social situations that would limit compliance with study requirements
Concomitant use of known strong cytochrome (CYP) 3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout period prior to starting study treatments is 2 weeks for strong inhibitors, and at least 1 week for moderate inhibitors
Concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout period prior to starting study treatments is 5 weeks for enzalutamide or phenobarbital and 4 weeks for other agents
 Pregnant women are excluded from this study because cediranib and olaparib are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with cediranib and olaparib, breastfeeding should be discontinued if the mother is treated with cediranib or olaparib; these potential risks may also apply to other agents used in this study; for women of child bearing capacity a negative pregnancy test is required
Known human immunodeficiency virus (HIV)-positive individuals are ineligible because of the potential for pharmacokinetic interactions with cediranib or olaparib; in addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy
Known active hepatitis B or hepatitis C infection on antiviral treatment
Prior history of stroke or transient ischemic attack within the last 6 months
Patients with any of the following:
- History of myocardial infarction within 6 months prior to starting treatment
- Unstable angina
- Prior history of hypertensive crisis or hypertensive encephalopathy
- Major surgical procedure within 2 weeks prior to starting treatment; patients must have recovered from any effects of any major surgery and surgical wound should have healed prior to starting treatment
- History of intra-abdominal abscess within 3 months prior to starting treatment
Patients may not use any complementary or alternative medicines including natural herbal products or folk remedies as they may interfere with the effectiveness of the study treatments
No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUBCT)
Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)
Patients with myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
Central nervous system metastases
Other malignancy within the last 5 years except for:
- Curatively treated basal cell or squamous cell carcinoma of skin; in situ cancer of the cervix, ductal carcinoma in situ of the breast or stage 1, grade 1 endometrial carcinoma
- Curatively treated other solid tumors including lymphomas (without bone marrow involvement) with no evidence of disease for >= 5 years prior to start of IPs
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or olaparib

Updated on 07 Jul 2023. Study ID: 1904481446 (NRG-GY012)

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