Trial of Letrozole + Palbociclib/Placebo in Metastatic Endometrial Cancer
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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:
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Number of prior lines of therapy (primary advanced disease vs. 1st relapse vs. ≥2 relapses)
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Measurable vs. evaluable disease
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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:
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Arm A: (comparator) letrozole-placebo combination therapy until progression.
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Arm B: (experimental arm): Letrozole- palbociclib combination therapy until progression
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Letrozole + placebo 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 is standard of care in both arms
|
| Experimental: Letrozole + palbociclib 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
Palbociclib or a placebo is administered together with standard of care letrozole
Drug: Letrozole
Letrozole is standard of care in both arms
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS). Increase in median PFS in experimental arm versus comparator arm [26 months]
To be measured (in months) and reported
Secondary Outcome Measures
- PFS of patients in the sub-populations as described under stratification factors. Increase in median PFS in experimental arm versus comparator arm [26 months]
To be measured (in months) and reported
- Overall Response Rate (ORR) according to RECIST [26 months]
To be measured (in %) and reported
- Disease Control Rate (DCR) for at least 12 weeks [26 months]
To be measured (in %) and reported
- Time to First Subsequent Therapy (TFST) [36 months]
TFST: time from randomization to first subsequent therapy or death. To be measured (in months) and reported
- Progression-Free Survival 2 (PFS2) [48 months]
PFS2: time from randomization to second objective disease progression or death. To be measured (in months) and reported
- Time to Second Subsequent Therapy (TSST) [48 months]
TSST: time from randomization to second subsequent therapy or death.To be measured (in months) and reported
- Patient Reported Outcomes (PROs) like Quality of Life questionnaire EORTC-QLQ-C30 & EORTC-QLQ-EN24 [48 months]
These are the validated questionnaires to be answered by patients. Results to be reported as descriptive and on a scale of 1-10
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [48 months]
To be reported on %
- Compliance in the two treatment arms. [48 months]
Missed dosages in both arm will be reported.
- Dose reductions/interruptions in the two treatment arms [48 months]
To be reported on %
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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Patients may have received adjuvant chemotherapy for stage 1 or 2.
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Patients may have received any lines of chemotherapy for primary advanced (stage 3-4) or relapsed disease.
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Patients may have received external beam radiotherapy, brachytherapy, and surgery.
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Patient may have received maximum one line of endocrine therapy containing MPA/Megace only.
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Patients must have measureable disease or evaluable disease on CT scan according to RECIST 1.1 outside irradiated field.
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Patients must give informed consent
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Patients must have a WHO performance status of 0-1
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Patients must have an adequate bone-marrow, renal and hepatic function
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Life expectancy of at least 12 weeks
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Patients must be fit to receive combination therapy
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Patient's age >18 years
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Patient is post-menopausal. Patients under the age of 55 with intact ovaries shall undergo hormonal verification.
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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:
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Non-endometrioid adenocarcinomas, sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers.
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Previous anti-cancer endocrine therapy other than MPA/Megace. This means that eg. tamoxifen is not allowed prior to study entry.
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Concurrent cancer therapy
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Previous treatment with Palbociclib or other CDK inhibitors.
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Concurrent treatment with an investigational anticancer agent or participation in another anticancer clinical trial within 21 days before entering into study.
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Treatment within 21 days prior to randomization with any investigational drug, radiotherapy,
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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.
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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.
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Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed.
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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.
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Known uncontrolled hypersensitivity to the investigational drugs.
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History of major thromboembolic event defined as:
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History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months.
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History of clinically significant hemorrhage in the past 3 months.
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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).
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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.
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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.
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Active or chronic hepatitis C and/or B infection
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Persistence of clinically relevant grade 3-4 therapy related toxicity from previous chemo and/or radiotherapy
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Known hypersensitivity to the trial drugs, or to their excipients.
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Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
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Unable or unwilling to swallow tablets/capsules
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | NSGO-CTU | Copenhagen | Sjaelland | Denmark | 2100 |
Sponsors and Collaborators
- Nordic Society of Gynaecological Oncology - Clinical Trials Unit
- European Network of Gynaecological Oncological Trial Groups (ENGOT)
- Gynecologic Cancer Intergroup (GCIG)
- North Eastern German Society of Gynaecological Oncology
- Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO)
- Grupo Español de Investigación en Cáncer de Ovario
Investigators
- Study Chair: Mansoor R Mirza, MD, NSGO
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ENGOT-EN3-NSGO/PALEO