Trial of Letrozole + Palbociclib/Placebo in Metastatic Endometrial Cancer

NCT02730429 | Completed Phase 2 DMC

• 1 other identifier: ENGOT-EN3-NSGO/PALEO
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized double-blind, placebo-controlled phase 2 trial is evaluating superiority of Letrozole-palbociclib combination versus letrozole-placebo combination in ER positive endometrioid adenocarcinoma of endometrium

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS). Increase in median PFS in experimental arm versus comparator arm

  To be measured (in months) and reported

  26 months

Secondary Outcomes (10)

• PFS of patients in the sub-populations as described under stratification factors. Increase in median PFS in experimental arm versus comparator arm

  26 months

• Overall Response Rate (ORR) according to RECIST

  26 months

• Disease Control Rate (DCR) for at least 12 weeks

  26 months

• Time to First Subsequent Therapy (TFST)

  36 months

• Progression-Free Survival 2 (PFS2)

  48 months

Study Arms (2)

Letrozole + placebo

PLACEBO COMPARATOR

letrozole 2.5mg once daily days 1-28 every 28 days shall be administered until progression of disease or unacceptable toxicity. Letrozole is administered as standard of care in both study arms. Placebo for palbociclib once daily days 1-21 every 28 days shall be administered until progression of disease or unacceptable toxicity.

Drug: Letrozole

Letrozole + palbociclib

EXPERIMENTAL

Palbociclib 125mg once daily days 1-21 every 28 days shall be administered until progression of disease or unacceptable toxicity. letrozole 2.5mg once daily days 1-28 every 28 days shall be administered until progression of disease or unacceptable toxicity. Letrozole is administered as standard of care in both study arms.

Drug: Palbociclib/placebo; Drug: Letrozole

Interventions

Palbociclib/placebo DRUG

Palbociclib or a placebo is administered together with standard of care letrozole

Letrozole + palbociclib

Letrozole DRUG

Letrozole is standard of care in both arms

Letrozole + palbociclib; Letrozole + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmed endometrial cancer of endometrioid type. Mixed tumor histology is allowed if the non-endometrioid component is less than 5%. Tumor must be estrogen receptor positive.
• Patients may have received adjuvant chemotherapy for stage 1 or 2.
• Patients may have received any lines of chemotherapy for primary advanced (stage 3-4) or relapsed disease.
• Patients may have received external beam radiotherapy, brachytherapy, and surgery.
• Patient may have received maximum one line of endocrine therapy containing MPA/Megace only.
• Patients must have measureable disease or evaluable disease on CT scan according to RECIST 1.1 outside irradiated field.
• Patients must give informed consent
• Patients must have a WHO performance status of 0-1
• Patients must have an adequate bone-marrow, renal and hepatic function
• Life expectancy of at least 12 weeks
• Patients must be fit to receive combination therapy
• Patient's age \>18 years
• Patient is post-menopausal. Patients under the age of 55 with intact ovaries shall undergo hormonal verification.
• Patients with preserved reproductive capacity must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment

You may not qualify if:

• Non-endometrioid adenocarcinomas, sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers.
• Previous anti-cancer endocrine therapy other than MPA/Megace. This means that eg. tamoxifen is not allowed prior to study entry.
• Concurrent cancer therapy
• Previous treatment with Palbociclib or other CDK inhibitors.
• Concurrent treatment with an investigational anticancer agent or participation in another anticancer clinical trial within 21 days before entering into study.
• Treatment within 21 days prior to randomization with any investigational drug, radiotherapy,
• Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
• Previous malignant disease, except patients with other malignant disease, for which the patient has been disease-free for at least three years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
• Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed.
• Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study.
• Known uncontrolled hypersensitivity to the investigational drugs.
• History of major thromboembolic event defined as:
• History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months.
• History of clinically significant hemorrhage in the past 3 months.
• Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization).

Sponsors & Collaborators

• Nordic Society of Gynaecological Oncology - Clinical Trials Unit: lead
• European Network of Gynaecological Oncological Trial Groups (ENGOT): collaborator
• Gynecologic Cancer Intergroup (GCIG): collaborator
• North Eastern German Society of Gynaecological Oncology: collaborator
• Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO): collaborator
• Grupo Español de Investigación en Cáncer de Ovario: collaborator

Study Sites (1)

NSGO-CTU

Copenhagen, Region Sjælland, 2100, Denmark

Location

Related Publications (1)

• Mirza MR, Bjorge L, Marme F, Christensen RD, Gil-Martin M, Auranen A, Ataseven B, Rubio MJ, Salutari V, Luczak AA, Runnebaum IB, Redondo A, Lindemann K, Trillsch F, Ginesta MPB, Roed H, Kurtz JE, Petersson KS, Nyvang GB, Sehouli J. Palbociclib plus letrozole in estrogen receptor-positive advanced/recurrent endometrial cancer: Double-blind placebo-controlled randomized phase II ENGOT-EN3/PALEO trial. Gynecol Oncol. 2025 Jan;192:128-136. doi: 10.1016/j.ygyno.2024.12.003. Epub 2024 Dec 9.

  PMID: 39657575 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

palbociclib; Letrozole

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mansoor R Mirza, MD

  NSGO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: April 6, 2016
• Study Start: February 15, 2017
• Primary Completion: December 15, 2020
• Study Completion: December 15, 2021
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)