What side effects are associated with this type of intervention?

The most common treatments for Endometrioid Adenocarcinoma, particularly those involving enzyme inhibition like Cediranib Maleate and Olaparib, are associated with several side effects. Cediranib Maleate, a VEGF inhibitor, commonly causes hypertension, fatigue, diarrhea, and hypothyroidism. Olaparib, a PARP inhibitor, frequently results in nausea, fatigue, anemia, and neutropenia. Patients undergoing these treatments should be monitored for these side effects to manage them effectively.

What prior FDA approvals exist?

For the treatment of Endometrioid Adenocarcinoma, the FDA has approved several drugs that target specific pathways. Notably, Pembrolizumab, an immune checkpoint inhibitor, has been approved for use in combination with Lenvatinib, a multi-kinase inhibitor, for patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This combination targets the PD-1/PD-L1 pathway and multiple receptor tyrosine kinases, respectively. While not directly the same as Cediranib Maleate and Olaparib, which target angiogenesis and PARP enzymes, respectively, these treatments similarly focus on inhibiting specific enzymes and pathways to manage cancer progression.

What other types of research exist?

Promising novel alternatives for Endometrioid Adenocarcinoma patients include: 1) Pembrolizumab, an immune checkpoint inhibitor, which has shown efficacy in various cancers including endometrial cancer. 2) Combination therapies involving Bevacizumab and Temsirolimus, which have demonstrated potential in recurrent or persistent endometrial carcinoma. 3) Targeted therapies such as Rucaparib and Niraparib, PARP inhibitors that have shown activity in cancers with specific genetic mutations. These alternatives are based on recent clinical trials and advancements in the treatment of endometrial cancer.

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Tyrosine Kinase Inhibitor

Cediranib + Olaparib for Recurrent Ovarian Cancer

Phase 2 & 3

Waitlist Available

Led By Jung-min Lee

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Phase II study: measurable disease by RECIST 1.1 criteria; if archival tumor sample is not available tumor sample from fresh biopsy is acceptable

Patients must have histologically or cytologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer

Must not have

Dependency on IV hydration or total parenteral nutrition (TPN)

History of certain cardiac conditions

Timeline

Screening 3 weeks

Treatment Varies

Follow Up time from study enrollment to the onset of progression as determined by response evaluation criteria in solid tumors version 1.1 (recist) criteria, or death due to any cause, whichever occurs first, assessed up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two oral drugs, cediranib maleate and olaparib, alone or together, against standard chemotherapy for patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer that did not respond to previous treatments. The drugs aim to block enzymes needed for cancer cell growth. The goal is to see if these drugs are more effective than standard chemotherapy.

Who is the study for?

This trial is for adults with recurrent ovarian, fallopian tube, or primary peritoneal cancer that's resistant to platinum-based chemotherapy. Participants must not have used anti-angiogenic agents or PARP-inhibitors before and should be able to take oral medications. They need a good performance status (ECOG 0-2), controlled blood pressure and thyroid function, no severe cardiac history or untreated brain metastases, and can't be HIV-positive or pregnant.

What is being tested?

The study tests if cediranib maleate combined with olaparib is more effective than each drug alone or standard chemotherapy in treating certain cancers. It examines how these drugs block enzymes needed for tumor growth versus how chemo stops cell division/spread. The trial includes imaging tests like CT and MRI to monitor the disease.

What are the potential side effects?

Potential side effects include gastrointestinal issues due to oral medication intake, high blood pressure requiring control measures, possible impact on thyroid function needing monitoring, as well as general risks associated with taking cancer treatment drugs such as fatigue, nausea, and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer can be measured and I can provide a recent or new biopsy sample if needed.

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I have been diagnosed with ovarian, peritoneal, or fallopian tube cancer.

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I can take pills and don’t have stomach issues affecting medicine absorption.

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I do not have untreated brain tumors or symptoms from brain or spinal cord tumors.

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I can take care of myself but may not be able to do heavy physical work.

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I do not have HIV.

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I am 18 years old or older.

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I am not taking any strong medication that affects liver enzymes.

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I do not have signs of MDS or AML.

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I have not had a bone marrow or cord blood transplant.

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I have no history of heart conditions.

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I have had 3 or fewer previous cancer treatments.

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My cancer has returned and does not respond well to platinum-based treatments.

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My blood pressure is under control.

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I do not use herbal or alternative medicines.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I rely on IV fluids or nutrition through a vein.

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I have a history of heart problems.

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I have signs of MDS or AML.

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I have previously used PARP-inhibitors.

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My cancer is indicated by CA-125 levels without measurable tumors.

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I have had treatments targeting blood vessel growth in my cancer before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ time from study enrollment to the onset of progression as determined by response evaluation criteria in solid tumors version 1.1 (recist) criteria, or death due to any cause, whichever occurs first, assessed up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~time from study enrollment to the onset of progression as determined by response evaluation criteria in solid tumors version 1.1 (recist) criteria, or death due to any cause, whichever occurs first, assessed up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and time from study enrollment to the onset of progression as determined by response evaluation criteria in solid tumors version 1.1 (recist) criteria, or death due to any cause, whichever occurs first, assessed up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival (OS) (Phase III)

Progression-free survival (PFS) (Phase II and Phase III)

Secondary study objectives

Incidence of adverse events (Phase II and Phase III)

Objective response rate (partial or complete response) (Phase II and Phase III)

Other study objectives

Biomarkers in plasma angiome

Change in circulating endothelial cell levels

Gene mutations assessed BROCA-HR

+1 more

Side effects data

From 2015 Phase 2 & 3 trial • 1814 Patients • NCT00384176

77%

Diarrhoea

52%

Nausea

48%

Hypertension

47%

Fatigue

45%

Neutropenia

40%

Stomatitis

37%

Decreased Appetite

34%

Vomiting

29%

Thrombocytopenia

26%

Neuropathy Peripheral

26%

Abdominal Pain

25%

Dysphonia

24%

Headache

24%

Epistaxis

24%

Paraesthesia

19%

Peripheral Sensory Neuropathy

18%

Constipation

17%

Weight Decreased

16%

Palmar-Plantar Erythrodysaesthesia Syndrome

16%

Asthenia

14%

Dyspnoea

14%

Pyrexia

13%

Dysgeusia

13%

Hypothyroidism

12%

Proteinuria

12%

Cough

11%

Abdominal Pain Upper

11%

Nasopharyngitis

10%

Leukopenia

10%

Back Pain

Alopecia

Urinary Tract Infection

Hypokalaemia

Pain In Extremity

Anaemia

Dizziness

Insomnia

Arthralgia

Rash

Oropharyngeal Pain

Oedema Peripheral

Alanine Aminotransferase Increased

Lethargy

Myalgia

Depression

Dysphagia

Dyspepsia

Drug Hypersensitivity

Dry Mouth

Phlebitis

Musculoskeletal Pain

Dehydration

Pulmonary Embolism

Upper Respiratory Tract Infection

Non-Cardiac Chest Pain

Abdominal Infection

Cognitive Disorder

Abdominal Abscess

Atrial Flutter

Ileus

Oesophagitis

Embolism Venous

Gastrointestinal Pain

Angina Pectoris

Rectal Haemorrhage

Sepsis

Supraventricular Tachycardia

Lobar Pneumonia

Transient Ischaemic Attack

Cerebrovascular Accident

Renal Failure

Vena Cava Thrombosis

Pneumonia

Pharyngeal Oedema

Hypercalcaemia

Haematuria

General Physical Health Deterioration

Left Ventricular Dysfunction

Catheter Related Infection

Pleural Effusion

Cerebral Haemorrhage

Agranulocytosis

Intestinal Perforation

Convulsion

Deep Vein Thrombosis

Cardiomyopathy

Enteritis

Gastrointestinal Toxicity

Ileus Paralytic

Large Intestinal Obstruction

Appendicitis

Bronchitis

Catheter Site Cellulitis

Neutropenic Sepsis

Pulmonary Tuberculosis

Syncope

Cerebral Ischaemia

Haemorrhagic Stroke

Vascular Encephalopathy

Subclavian Vein Thrombosis

Thrombosis

Cardiopulmonary Failure

Mitral Valve Incompetence

Myocardial Ischaemia

Intestinal Haemorrhage

Bradyphrenia

Hypertensive Crisis

Febrile Neutropenia

Pancytopenia

Intestinal Obstruction

Gastrointestinal Inflammation

Large Intestine Perforation

Death

100%

80%

60%

40%

20%

Study treatment Arm

Cediranib 30 mg

1Bevacizumab 5mg/kg

Cediranib 20 mg

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

7Treatment groups

Experimental Treatment

Active Control

Group I: Phase III Arm III (single-agent cediranib maleate)Experimental Treatment5 Interventions

Patients receive cediranib maleate PO as determined by the Phase II study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.

Group II: Phase III Arm II (cediranib maleate, olaparib)Experimental Treatment6 Interventions

Patients receive cediranib maleate PO and olaparib PO as in Phase II Arm II. Patients also undergo CT and MRI throughout the study.

Group III: Phase II Arm IV (olaparib)Experimental Treatment4 Interventions

Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study. (In July 2018, the Data Monitoring Committee voted to exclude the olaparib alone regimen).

Group IV: Phase II Arm III (cediranib maleate)Experimental Treatment5 Interventions

Patients receive cediranib maleate PO daily continuously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.

Group V: Phase II Arm II (cediranib maleate, olaparib)Experimental Treatment6 Interventions

Patients receive cediranib maleate PO QD and olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the study.

Group VI: Phase III Arm I (reference regimen)Active Control7 Interventions

Patients undergo physician's choice standard of care chemotherapy as in Phase II Arm I. No modification of the assigned regimens, such as additional drugs (gemcitabine or bevacizumab) is allowed. Patients also undergo CT and MRI throughout the study. (12/05/2016)

Group VII: Phase II Arm I (reference regimen)Active Control7 Interventions

Patients undergo physician's choice of standard of care chemotherapy, comprising either paclitaxel IV over 60 minutes on days 1, 8, 15, and 22 every 28 days (Regimen I); pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 every 28 days (Regimen II); or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15 every 28 days or days 1-5 every 21 days (Regimen III). Treatment continues in the absence of disease progression or unacceptable toxicity. No modification of the assigned regimens, such as additional drugs (gemcitabine, or bevacizumab) is allowed. Patients also undergo CT and MRI throughout the study. (12/05/2016)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

2007

Completed Phase 4

~2190

Cediranib Maleate

2010

Completed Phase 2

~660

Computed Tomography

2017

Completed Phase 2

~2790

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

Cediranib

2016

Completed Phase 3

~4030

0 / 21Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Endometrioid Adenocarcinoma, such as Cediranib Maleate and Olaparib, work by inhibiting specific enzymes crucial for cancer cell survival. Cediranib Maleate targets VEGFR to reduce tumor blood supply, while Olaparib inhibits PARP, preventing DNA repair in cancer cells. These targeted therapies are important for patients as they can enhance treatment effectiveness and minimize side effects compared to conventional chemotherapy.

Clinical Benefits of Olaparib in Mexican Ovarian Cancer Patients With Founder Mutation BRCA1-Del ex9-12.Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol.Antitumor activity of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy in patients with platinum-sensitive, relapsed, BRCA-mutated, high-grade ovarian cancer, and an update on safety.