Trial of Letrozole + Palbociclib/Placebo in Metastatic Endometrial Cancer

Endometrial Cancer Clinical Trial

Official title:

ENGOT-EN3-NSGO/PALEO: A Randomized, Double-blind, Placebo-controlled, Phase II Trial of Palbociclib in Combination With Letrozole Versus Placebo in Combination With Letrozole for Patients With Estrogen Receptor Positive Advanced or Recurrent Endometrial Cancer.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02730429
• Other study ID #: ENGOT-EN3-NSGO/PALEO
• Status: Completed
• Phase: Phase 2
• Start date: February 15, 2017
• Est. completion date: December 15, 2021

Study information

• Verified date: February 2023
• Source: Nordic Society of Gynaecological Oncology - Clinical Trials Unit
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

This multicenter, prospective, randomized, double-blind, placebo-controlled phase 2 study is evaluating the efficacy of letrozole-palbociclib combination against letrozole-placebo combination in women with ER+ advanced or relapsed endometrial cancer.

Stratification

Patients are stratified according to:

1. Number of prior lines of therapy (primary advanced disease vs. 1st relapse vs. ≥2 relapses)

2. Measurable vs. evaluable disease

3. Prior use of MPA/Megace

Randomization 1:1 randomization The patients with prior MPA/Megace treatment will be capped to a maximum of 50%.

Study arms

Patients are randomized to one of the two treatment arms:

• Arm A: (comparator) letrozole-placebo combination therapy until progression.

• Arm B: (experimental arm): Letrozole- palbociclib combination therapy until progression

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: December 15, 2021
• Est. primary completion date: December 15, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Patients may have received adjuvant chemotherapy for stage 1 or 2.

3. Patients may have received any lines of chemotherapy for primary advanced (stage 3-4) or relapsed disease.

4. Patients may have received external beam radiotherapy, brachytherapy, and surgery.

5. Patient may have received maximum one line of endocrine therapy containing MPA/Megace only.

6. Patients must have measureable disease or evaluable disease on CT scan according to RECIST 1.1 outside irradiated field.

7. Patients must give informed consent

8. Patients must have a WHO performance status of 0-1

9. Patients must have an adequate bone-marrow, renal and hepatic function

10. Life expectancy of at least 12 weeks

11. Patients must be fit to receive combination therapy

12. Patient's age >18 years

13. Patient is post-menopausal. Patients under the age of 55 with intact ovaries shall undergo hormonal verification.

14. Patients with preserved reproductive capacity must have a negative pregnancy test (ß-HCG test in urine or serum) prior to commencing study treatment

Exclusion Criteria:

1. Non-endometrioid adenocarcinomas, sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers.

2. Previous anti-cancer endocrine therapy other than MPA/Megace. This means that eg. tamoxifen is not allowed prior to study entry.

3. Concurrent cancer therapy

4. Previous treatment with Palbociclib or other CDK inhibitors.

5. Concurrent treatment with an investigational anticancer agent or participation in another anticancer clinical trial within 21 days before entering into study.

6. Treatment within 21 days prior to randomization with any investigational drug, radiotherapy,

7. 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.

8. 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.

9. Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed.

10. 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.

11. Known uncontrolled hypersensitivity to the investigational drugs.

12. History of major thromboembolic event defined as:

13. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months.

14. History of clinically significant hemorrhage in the past 3 months.

15. 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).

16. Significant cardiovascular diseases, including uncontrolled hypertension, uncontrolled clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > NYHA III, severe peripheral vascular disease, clinically significant pericardial effusion.

17. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards.

18. Active or chronic hepatitis C and/or B infection

19. Persistence of clinically relevant grade 3-4 therapy related toxicity from previous chemo and/or radiotherapy

20. Known hypersensitivity to the trial drugs, or to their excipients.

21. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug

22. Unable or unwilling to swallow tablets/capsules

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• Palbociclib/placebo
Palbociclib or a placebo is administered together with standard of care letrozole
• Letrozole
Letrozole is standard of care in both arms

Locations

Country	Name	City	State
Denmark	NSGO-CTU	Copenhagen	Sjaelland

Sponsors (6)

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

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS). Increase in median PFS in experimental arm versus comparator arm	To be measured (in months) and reported	26 months
Secondary	PFS of patients in the sub-populations as described under stratification factors. Increase in median PFS in experimental arm versus comparator arm	To be measured (in months) and reported	26 months
Secondary	Overall Response Rate (ORR) according to RECIST	To be measured (in %) and reported	26 months
Secondary	Disease Control Rate (DCR) for at least 12 weeks	To be measured (in %) and reported	26 months
Secondary	Time to First Subsequent Therapy (TFST)	TFST: time from randomization to first subsequent therapy or death. To be measured (in months) and reported	36 months
Secondary	Progression-Free Survival 2 (PFS2)	PFS2: time from randomization to second objective disease progression or death. To be measured (in months) and reported	48 months
Secondary	Time to Second Subsequent Therapy (TSST)	TSST: time from randomization to second subsequent therapy or death.To be measured (in months) and reported	48 months
Secondary	Patient Reported Outcomes (PROs) like Quality of Life questionnaire EORTC-QLQ-C30 & EORTC-QLQ-EN24	These are the validated questionnaires to be answered by patients. Results to be reported as descriptive and on a scale of 1-10	48 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	To be reported on %	48 months
Secondary	Compliance in the two treatment arms.	Missed dosages in both arm will be reported.	48 months
Secondary	Dose reductions/interruptions in the two treatment arms	To be reported on %	48 months