What side effects are associated with this type of intervention?

Common treatments for endometrial cancer, particularly those involving inhibition of anti-apoptotic proteins and kinase inhibition, can have several side effects. These may include fatigue, nausea, diarrhea, and skin rashes. Additionally, patients might experience more severe effects such as liver toxicity, hypertension, and increased risk of infections due to immunosuppression. Endocrine therapies, often used in hormone receptor-positive cancers, can cause weight gain, hot flashes, and thromboembolic events. Chemotherapy, another common treatment, typically results in hair loss, myelosuppression, and gastrointestinal disturbances.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of endometrial cancer, though specific approvals for drugs that inhibit anti-apoptotic proteins and kinase inhibitors are limited. One notable kinase inhibitor is Pembrolizumab, which targets PD-1 and has shown efficacy in various cancers, including endometrial cancer. Additionally, mTOR inhibitors like Everolimus have been studied in combination with aromatase inhibitors for their potential benefits in endometrial cancer. While these drugs do not directly match the mechanisms of Pelcitoclax and Cobimetinib, they represent the broader category of targeted therapies and kinase inhibitors used in endometrial cancer treatment.

What other types of research exist?

Promising novel alternatives for endometrial cancer treatment in 2024 include: 1) Pembrolizumab, a PD-1 inhibitor, which has shown efficacy in various cancers including endometrial cancer. 2) Lenvatinib, a multi-kinase inhibitor, often used in combination with pembrolizumab. 3) PARP inhibitors like Olaparib, especially for patients with specific genetic mutations. 4) Novel combinations of immunotherapies and targeted therapies, such as combining checkpoint inhibitors with anti-angiogenic agents.

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Protein Inhibitor

Pelcitoclax + Cobimetinib for Recurrent Ovarian and Endometrial Cancers

Phase 1

Recruiting

Led By Joyce F Liu

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

Patients must have histologically or cytologically confirmed recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, or metastatic or unresectable endometrial cancer with no standard curative or palliative measures available

Patients with low grade serous ovarian cancer must have received a prior MEK inhibitor at a demonstrated therapeutic dose

Must not have

History of allergic reactions attributed to compounds of similar chemical or biologic composition to APG-1252 or cobimetinib

Patients with uncontrolled intercurrent illness

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests the safety and best dose of two drugs, pelcitoclax and cobimetinib, in patients with recurring ovarian and endometrial cancers. Pelcitoclax helps kill cancer cells, and cobimetinib slows their growth. The goal is to find an effective dose and observe how well the combination works in shrinking or stabilizing tumors.

Who is the study for?

This trial is for adults with recurrent ovarian or endometrial cancer who've had platinum-based therapy and, if applicable, specific prior treatments based on their cancer type. They must be able to take oral meds, provide tissue samples if available, use contraception if needed, and have no other health issues that could interfere.

What is being tested?

The trial tests a combo of two drugs: Pelcitoclax (APG-1252) which may help kill cancer cells by blocking certain proteins, and Cobimetinib which targets abnormal proteins in cancers with a BRAF gene mutation. The goal is to see if this drug duo can shrink or stabilize the tumors.

What are the potential side effects?

Potential side effects include reactions related to cell death such as fatigue and nausea; kinase inhibitors like Cobimetinib might cause skin rash, vision changes or liver problems. Each patient's reaction will vary.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has returned or spread and cannot be surgically removed, with no standard treatments left.

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I have low grade serous ovarian cancer and have been treated with a MEK inhibitor.

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I have had platinum-based chemotherapy before, not just with radiation.

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My cancer can be measured and biopsied.

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I am mostly self-sufficient and can carry out daily activities.

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I am 18 years old or older.

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I can swallow pills.

Exclusion Criteria

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

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I am allergic to medications similar to APG-1252 or cobimetinib.

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I do not have any unmanaged ongoing illnesses.

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I have a stomach or intestine condition that affects how I absorb pills.

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I am not taking strong CYP3A4 inhibitors or inducers.

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I rely on IV fluids or nutrition through a vein.

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I have been treated with BCL family inhibitors before.

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I have retinal problems detected by an eye exam.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

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

Incidence of dose-limiting toxicities (DLTs)

Maximum tolerable dose

Recommended phase 2 dose

Secondary study objectives

Clinical benefit rate

Duration of response (DoR)

Incidence of adverse events

+3 more

Other study objectives

Effect of combination APG-1252 and cobimetinib on RAS pathway signaling

Markers of response and resistance to APG-1252 and cobimetinib

Markers of response and resistance to APG-1252 and cobimetinib via sequencing

+1 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (pelcitoclax, cobimetinib)Experimental Treatment8 Interventions

Patients receive APG-1252 IV Q7D. Patients also receive cobimetinib PO QD on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy and collection of blood on study and undergo CT and/or MRI throughout the trial. Patients undergo ECHO or MUGA during screening and on study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cobimetinib

2017

Completed Phase 3

~3630

Biopsy

2014

Completed Phase 4

~1090

Biospecimen Collection

2004

Completed Phase 3

~2020

Echocardiography

2013

Completed Phase 4

~11580

Computed Tomography

2017

Completed Phase 2

~2740

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Multigated Acquisition Scan

2015

Completed Phase 3

~270

0 / 14Eligibility 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 endometrial cancer include chemotherapy, hormone therapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, while hormone therapy targets hormone receptor-positive tumors by blocking hormones like estrogen. Targeted therapies, such as kinase inhibitors like Cobimetinib, block specific proteins that signal cancer cells to grow, thereby slowing or stopping tumor growth. Inhibition of anti-apoptotic proteins, as seen with Pelcitoclax (APG-1252), promotes cancer cell death by preventing the proteins that usually protect cancer cells from dying. These mechanisms are crucial for endometrial cancer patients as they offer tailored treatment options that can be more effective and potentially have fewer side effects compared to traditional therapies.

Efficacy of afatinib in a HER2 amplification-positive endometrioid adenocarcinoma patient- a case report.