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RESOLVE: Abemaciclib + Letrozole +/- Metformin or Gedatolisib in Endometrial Cancer

ConditionEndometrial Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorDana-Farber Cancer Institute

About this trial

This research study is studying a combination of targeted therapies as a possible treatment for estrogen-receptor positive (ER+) endometrial cancer.

The drugs involved in this study are:

* Abemaciclib (also known as Verzenio™) * Letrozole (also known as Femara®) * Metformin (also known as Glucophage®) * Gedatolisib (also known as PF-05212384)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Participants must have cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies, or for which no standard therapy is available. Participants enrolled in the second stage of Cohort 1A, or into Cohort 3, 6 and 7, must have histologically confirmed either i) endometrioid endometrial cancer or ii) endometrial carcinosarcoma with endometrioid epithelial component

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.

Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.

Age ≥ 18 years

Disqualifiers

Participants who have had chemotherapy, immune therapy, other investigational therapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose of study medication. Previous hormonal therapy, including prior letrozole, is allowed and there is no required washout period for hormonal therapy.

Participants who have had tyrosine kinase inhibitor (TKI) therapy within 5 half-lives of study entry.

Participants who have had radiation therapy within 2 weeks of the first dose of study medication.

Participants who have received previous treatment with CDK4/6 inhibitors, including but not limited to previous abemaciclib therapy. For Cohort 7, patients must have received prior treatment with CDK4/6 inhibitors.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Letrozole

    Drug

    Letrozole is a hormonal therapy that works by lowering the production of estrogen in the body.

  • Abemaciclib

    Drug

    Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor.

  • LY3023414

    Drug

    LY3023414 is a potent selective inhibitor of the class I PI3K isoforms, mTOR, and DNA-PK.

  • Metformin

    Drug

    Metformin inhibits mitochondrial adenosine-5'-triphosphate (ATP) synthesis, resulting in activation of the AMPK (5' AMP-activated protein kinase) pathway through LKB1, eventually causing inhibition of the mTOR pathway and subsequent reduction in protein synthesis and cellular proliferation.

  • Gedatolisib

    Drug

    Gedatolisib is a PI3K/AKT/mTOR (PAM) pathway inhibitor.

Treatment groups

110 Participants
are divided into 6 treatment groups

6

Treatment groups

See each treatment group below.

Group A: Cohort 1Experimental treatment 3 interventions
Group B: Cohort 2Experimental treatment 2 interventions
Group C: Cohort 1AExperimental treatment 2 interventions
Group D: Cohort 3Experimental treatment 3 interventions
Group E: Cohort 6Experimental treatment 3 interventions
Group F: Cohort 7Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Progression Free Survival Rate

Number of patients alive and disease progression-free per RECIST 1.1 criteria.

Time frame
6 months
2

Objective Tumor Response Rate

Number of patients who experience objective tumor responses per RECIST 1.1 criteria.

Time frame
6 months

Secondary outcomes

1

Overall Survival Rate

Length of time from study enrollment to death from any cause.

Time frame
3 years
2

Treatment-related toxicities

Toxicities measured by CTCAE version 5.0 criteria.

Time frame
3 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Dana-Farber Cancer Institute

Lead sponsor

Eli Lilly and Company

Collaborator

Celcuity Inc

Collaborator

Source ClinicalTrials.gov
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