← Back to Search

CDK4/6 Inhibitor

Abemaciclib + Letrozole +/- Metformin for Endometrial Cancer

Phase 2

Waitlist Available

Led By Panagiotis Konstantininopoulos, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

Participants must have ER-positive disease, defined as ≥ 1 percent of tumor cell nuclei being immunoreactive by immunohistochemistry (IHC). If multiple analyses have been performed, judgment should be based on the most recent biopsy or pathology specimen analyzed in a CLIA-certified laboratory

ECOG performance status of 0 or 1

Must not have

Participants who at the time of study enrollment are known to require concomitant therapy with moderate or strong CYP3A4 inducers, or strong inhibitors of CYP3A4. Due to potential drug interactions, concomitant use of these medications is not permitted for the duration of treatment on trial. Participants are eligible for study entry if an appropriate substitution is made prior to the first dose of study medication

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is looking at whether giving these drugs together might work better than giving letrozole alone.

Who is the study for?

This trial is for adults with measurable, estrogen-receptor positive endometrial cancer that's recurrent or resistant to standard treatments. They must have good organ and bone marrow function, no history of certain heart conditions or uncontrolled illnesses, and not be on conflicting medications. Women must use contraception and can't be pregnant or breastfeeding.

What is being tested?

The study tests a combination of targeted therapies: Abemaciclib (Verzenio™), Letrozole (Femara®), with or without Metformin (Glucophage®) as potential treatments for ER+ endometrial cancer. It aims to see how well these drugs work together in treating this type of cancer.

What are the potential side effects?

Potential side effects include digestive issues, blood sugar changes due to metformin; fatigue, diarrhea from abemaciclib; joint pain from letrozole; and the general risk of infection increase due to immune system impact by these therapies.

Eligibility Criteria

Inclusion Criteria

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

Select...

My cancer is estrogen receptor-positive.

Select...

I am fully active or can carry out light work.

Select...

My endometrial cancer has returned, spread, or doesn’t respond to standard treatments.

Select...

My cancer is confirmed as endometrioid endometrial or carcinosarcoma with an endometrioid part.

Select...

I have a tissue sample from a previous biopsy that can be used for analysis.

Select...

I have a tumor that can be measured with scans or exams.

Select...

I can swallow and keep down pills.

Select...

I am 18 years old or older.

Exclusion Criteria

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

Select...

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

Select...

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Select...

I have had heart problems or treatments within the last 6 months.

Select...

I am not pregnant or breastfeeding if I join this trial.

Select...

My high blood pressure is not controlled, even with medication.

Select...

I do not have HIV due to the risk of severe infections with treatment.

Select...

I have previously been treated with CDK4/6 inhibitors.

Select...

I do not have brain metastases.

Select...

I have not had radiation therapy in the last 2 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

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

Objective Tumor Response Rate

Progression Free Survival Rate

Secondary study objectives

Overall Survival Rate

Treatment-related toxicities

Side effects data

From 2018 Phase 2 trial • 132 Patients • NCT02102490

91%

Diarrhoea

67%

Nausea

48%

Fatigue

45%

Decreased appetite

35%

Vomiting

27%

Anaemia

26%

Abdominal pain

23%

Asthenia

23%

Neutrophil count decreased

21%

Cough

20%

Constipation

20%

Headache

19%

Arthralgia

18%

White blood cell count decreased

18%

Neutropenia

15%

Alopecia

14%

Dry mouth

14%

Platelet count decreased

14%

Weight decreased

14%

Dysgeusia

13%

Dyspnoea

12%

Abdominal pain upper

12%

Back pain

12%

Dizziness

11%

Oedema peripheral

11%

Dyspepsia

11%

Pyrexia

11%

Blood creatinine increased

10%

Pain

Stomatitis

Aspartate aminotransferase increased

Thrombocytopenia

Lacrimation increased

Dehydration

Dry skin

Pruritus

Alanine aminotransferase increased

Flatulence

Upper respiratory tract infection

Urinary tract infection

Hypokalaemia

Chills

Musculoskeletal chest pain

Musculoskeletal pain

Anxiety

Gastrooesophageal reflux disease

Rash

Myalgia

Cellulitis

Pleural effusion

Atypical pneumonia

Gastroenteritis viral

Lung infection

Sepsis

Fall

Hip fracture

Pneumonitis

Pneumothorax

Febrile neutropenia

Respiratory tract infection

Haematotoxicity

Sinus bradycardia

Tachycardia

Large intestinal obstruction

Pancreatic enzyme abnormality

Pancreatitis

Varices oesophageal

Electrocardiogram abnormal

Liver function test abnormal

Renal function test abnormal

Bone pain

Muscular weakness

Acute kidney injury

Pulmonary embolism

Arterial thrombosis

Epilepsy

100%

80%

60%

40%

20%

Study treatment Arm

Abemaciclib

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: Cohort 5Experimental Treatment3 Interventions

* Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily * Zotatifin is administered intravenously on days 1 and 8 of a 21-day cycle

Group II: Cohort 4Experimental Treatment3 Interventions

* Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily * Zotatifin is administered intravenously on days 1 and 8 of a 21-day cycle

Group III: Cohort 3Experimental Treatment3 Interventions

* Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily * Metformin is administered by mouth once daily

Group IV: Cohort 2Experimental Treatment2 Interventions

* Abemaciclib is administered by mouth twice daily * LY3023414 is administered by mouth twice daily

Group V: Cohort 1AExperimental Treatment2 Interventions

* Abemaciclib is administered by mouth twice daily * Letrozole is administered by mouth once daily

Group VI: Cohort 1Experimental Treatment3 Interventions

* Abemaciclib is administered by mouth twice daily * LY3023414 is administered by mouth twice daily * Letrozole is administered by mouth once daily

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug