Brief Title
Trial of Letrozole + Palbociclib/Placebo in Metastatic Endometrial Cancer
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.
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
Detailed 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
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression-Free Survival (PFS). Increase in median PFS in experimental arm versus comparator arm
Secondary Outcome
PFS of patients in the sub-populations as described under stratification factors. Increase in median PFS in experimental arm versus comparator arm
Condition
Endometrial Cancer
Intervention
Palbociclib/placebo
Study Arms / Comparison Groups
Letrozole + placebo
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
78
Start Date
February 15, 2017
Completion Date
December 2022
Primary Completion Date
December 15, 2018
Eligibility Criteria
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
(β-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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Mansoor R Mirza, MD, ,
Location Countries
Denmark
Location Countries
Denmark
Administrative Informations
NCT ID
NCT02730429
Organization ID
ENGOT-EN3-NSGO/PALEO
Responsible Party
Sponsor
Study Sponsor
Nordic Society of Gynaecological Oncology - Clinical Trials Unit
Collaborators
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Study Sponsor
Mansoor R Mirza, MD, Study Chair, NSGO
Verification Date
October 2019