What side effects are associated with this type of intervention?

Common treatments for endometrial carcinoma, such as Olaparib, Cediranib, Capivasertib, and Durvalumab, have distinct side effect profiles. Olaparib, a PARP inhibitor, often causes nausea, fatigue, vomiting, and anemia. Cediranib, a VEGFR inhibitor, can lead to hypertension, diarrhea, and fatigue. Capivasertib, an AKT inhibitor, may result in diarrhea, hyperglycemia, and rash. Durvalumab, a PD-L1 inhibitor, is associated with immune-related adverse events such as colitis, pneumonitis, and thyroid dysfunction. Patients should discuss these potential side effects with their healthcare provider to manage them effectively.

What prior FDA approvals exist?

As of now, the FDA has not specifically approved Olaparib, Cediranib, Capivasertib, or Durvalumab for the treatment of endometrial carcinoma. However, these drugs are being studied in clinical trials for their potential efficacy in treating this type of cancer. Generally, treatment for endometrial carcinoma may include hormonal therapies, chemotherapy, and targeted therapies, but the specific use of PARP inhibitors, VEGFR inhibitors, AKT inhibitors, and PD-L1 inhibitors in this context is still under investigation.

What other types of research exist?

Promising novel alternatives for Endometrial Carcinoma treatment in 2024 include Pembrolizumab (PD-1 inhibitor) combined with Lenvatinib (VEGFR inhibitor), which has shown significant improvements in progression-free survival. Additionally, antibody-drug conjugates and other immune checkpoint inhibitors like Nivolumab (PD-1 inhibitor) and combination therapies involving novel agents targeting the PI3K/AKT/mTOR pathway are also being explored.

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AKT Inhibitor

Drug Combinations for Endometrial Cancer

Phase 2

Waitlist Available

Led By Helen J Mackay

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

Adequately controlled thyroid function, with no symptoms of thyroid dysfunction

Patients must have evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or non-measurable (detectable) disease

Must not have

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

Prior history of stroke or transient ischemic attack within the last 6 months

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests different drug combinations to treat endometrial cancer that has come back or doesn't respond to usual treatments. The drugs work by either blocking enzymes needed for cancer growth or helping the immune system attack the cancer. The goal is to find the most effective treatment combination.

Who is the study for?

This trial is for women with certain types of recurrent or refractory endometrial cancer. Participants must have adequate organ function, controlled blood pressure, and no severe allergies to the drugs being tested. They should not be pregnant, must agree to use contraception, and cannot have had certain prior treatments or serious health conditions like bowel obstruction or heart issues.

What is being tested?

The study tests combinations of olaparib with durvalumab, cediranib with durvalumab, olaparib with capivasertib, and cediranib alone in patients whose endometrial cancer has returned or resisted treatment. These drugs aim to block tumor growth by targeting enzymes needed for cell growth or interfering with tumor cells' ability to spread.

What are the potential side effects?

Potential side effects include fatigue; nausea; diarrhea; high blood pressure; allergic reactions such as rashes; anemia (low red blood cell counts); neutropenia (low white blood cell counts), which can increase infection risk; liver enzyme changes suggesting liver injury.

Eligibility Criteria

Inclusion Criteria

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

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My thyroid function is normal, with no symptoms of issues.

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My cancer can be measured by standard criteria or is detectable.

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I have received one chemotherapy treatment for endometrial cancer, which may have included radiation.

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My endometrial cancer has come back or hasn't responded to treatment, and it's not clear cell type.

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My body weight is over 30 kg.

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I am 18 years old or older.

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My kidney function, measured by creatinine clearance, is good.

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I am postmenopausal or cannot become pregnant, confirmed by a recent test.

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I can swallow pills and don't have stomach issues affecting medicine absorption.

Exclusion Criteria

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

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I am not currently using strong or moderate drugs that affect liver enzymes.

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I have not had a stroke or a mini-stroke in the last 6 months.

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You have had a heart attack or unstable angina within the past 6 months, abnormal ECG findings, severe heart disease, a recent major surgery, or an abdominal abscess within the past 3 months.

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I have not had a whole blood transfusion in the last 4 months.

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My heart's pumping ability is below normal, and I've had specific heart-related treatments or conditions.

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I am not using any herbal or alternative medicines.

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I have or had an autoimmune disease that could worsen or needs steroids.

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I do not have an active infection, including tuberculosis.

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I am on antiviral treatment for active hepatitis B or C.

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

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I do not have any severe illnesses that could interfere with the study.

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I have been diagnosed with MDS, t-AML, or have symptoms suggesting these conditions.

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I do not have HIV due to potential drug interactions and increased infection risk.

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I have had more than one treatment with immune therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 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

Progression-free survival

Secondary study objectives

Incidence of adverse events

Objective tumor response

Overall survival

Other study objectives

Markers of angiogenesis in serial plasma samples

Awards & Highlights

No Placebo-Only Group

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

Trial Design

6Treatment groups

Experimental Treatment

Group I: Arm VI (cediranib maleate, durvalumab)Experimental Treatment8 Interventions

Patients receive cediranib maleate PO QD on days 1-5 each week and durvalumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.

Group II: Arm V (olaparib, durvalumab)Experimental Treatment8 Interventions

Patients receive olaparib PO BID on days 1-28 and durvalumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.

Group III: Arm IV (olaparib, capivasertib)Experimental Treatment8 Interventions

Patients receive olaparib PO BID on days 1-28 and capivasertib PO BID on days 1-4 each week. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.

Group IV: Arm III (cediranib maleate, olaparib)Experimental Treatment9 Interventions

Patients receive olaparib PO BID and cediranib maleate PO QD. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.

Group V: Arm II (olaparib)Experimental Treatment7 Interventions

Patients receive olaparib PO BID. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.

Group VI: Arm I (cediranib maleate)Experimental Treatment8 Interventions

Patients receive cediranib maleate PO QD. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy, CT, Echo or MUGA on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Computed Tomography

2017

Completed Phase 2

~2740

Durvalumab

2017

Completed Phase 2

~3750

Biospecimen Collection

2004

Completed Phase 3

~2020

Capivasertib

2021

Completed Phase 1

~130

Bone Marrow Aspirate

2015

Completed Phase 3

~40

Bone Marrow Biopsy

2021

Completed Phase 3

~230

Echocardiography

2013

Completed Phase 4

~11580

Cediranib

2016

Completed Phase 3

~4030

Cediranib Maleate

2010

Completed Phase 2

~660

Multigated Acquisition Scan

2015

Completed Phase 3

~270

Olaparib

2007

Completed Phase 4

~2190

0 / 23Eligibility 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

The most common treatments for Endometrial Carcinoma include targeted therapies such as Olaparib, Cediranib, Capivasertib, and Durvalumab. Olaparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, leading to cell death, particularly in tumors with existing DNA repair deficiencies. Cediranib inhibits VEGFR, blocking the blood supply to tumors and thereby inhibiting their growth. Capivasertib targets the AKT pathway, which is involved in cell proliferation and survival, thus reducing tumor growth. Durvalumab is a PD-L1 inhibitor that enhances the immune system's ability to recognize and destroy cancer cells. These mechanisms are crucial as they offer targeted approaches to disrupt cancer cell survival and proliferation, providing more effective and personalized treatment options for Endometrial Carcinoma patients.

Combined Strategies with Poly (ADP-Ribose) Polymerase (PARP) Inhibitors for the Treatment of Ovarian Cancer: A Literature Review.