Brief Title
Combination Chemotherapy With Nintedanib / Placebo in Endometrial Cancer
Official Title
ENGOT-EN1/FANDANGO: A Randomized Phase II Trial of First-line Combination Chemotherapy With Nintedanib / Placebo for Patients With Advanced or Recurrent Endometrial Cancer
Brief Summary
This study will evaluate the role of addition of an anti-angiogenic agent
(Nintedanib/placebo) to conventional combination chemotherapy as concomitant and maintenance
treatment in primary advanced or with first relapse of endometrial cancer.
Detailed Description
This multicenter, prospective, double-blind, placebo-controlled, randomised phase 2 study is
evaluating combination chemotherapy with nintedanib in patients with primary advanced stage
(3C2 & 4), or with first relapse of endometrial cancer.
Patients are stratified according to:
1. Stage of disease (stage 3C2 vs. stage 4 vs. recurrent disease)
2. Prior adjuvant chemotherapy (yes/no)
3. Disease status (Measurable disease vs. non-measurable /RECIST 1.1)
Patients are randomized to one of the two treatment arms 1:1 randomization:
- Arm A: Paclitaxel and Carboplatin (6 courses) and Nintedanib (until PD). (Experimental
arm)
- Arm B: Paclitaxel and Carboplatin (6 courses) and Placebo (until PD) (Control Arm)
Primary endpoint is PFS. 148 patients to be enrolled.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
PFS: Difference in months of Median Progression-Free Survival in experimental arm versus comparator arm
Secondary Outcome
PFS in the sub-populations as described under stratification factors
Condition
Endometrial Cancer
Intervention
Nintedanib or Placebo; Carboplatin, Paclitaxel
Study Arms / Comparison Groups
A: Nintedanib
Description: Nintedanib 200mg twice daily days 2-21 every 21 days for 6 courses during simultaneous treatment with carboplatin-paclitaxel; afterwards in maintenance 200mg twice daily days 1-21 every 21 days. Treatment continues until progression 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
148
Start Date
November 2016
Completion Date
July 2022
Primary Completion Date
March 2019
Eligibility Criteria
Inclusion Criteria:
1. Histological confirmed endometrial cancer. (FIGO 2009)
1. Stage 3C 2
2. Stage 4 A & B
3. Relapsed after adjuvant therapy for stage 1-3 disease
2. Patients may have undergone primary surgery.
3. Patients may have received adjuvant chemotherapy for stage 1 - 3.
4. Patients may have received vaginal brachytherapy
5. Patients may have received external beam radiotherapy. Patients who are to be enrolled
for stage 3C2 diseases are allowed to receive external beam radiotherapy prior to
trial entry.
6. Patients may have received hormonal treatment
7. Patients must have measurable disease or non-measurable disease on CT scan according
to RECIST 1.1 outside irradiated field. For stage 3C2 disease patients without
measureable or non-measureable disease are accepted.
8. Patients must give informed consent
9. ECOG performance status of 0 -1
10. Patients must have an adequate organ function
11. Life expectancy of at least 12 weeks
12. Patients must be fit to receive combination chemotherapy
13. Patient's age >18 years
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. Sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial
cancers.
2. Concurrent cancer therapy
3. Previous Chemotherapy for stage 4 disease or for relapsed disease.
4. Previous treatment with anti-angiogenic/anti VEGF therapy including nintedanib.
5. Concurrent treatment with an investigational agent or participation in another
clinical trial.
6. Treatment within 28 days prior to randomisation with any investigational drug,
radiotherapy, immunotherapy, chemotherapy, hormonal therapy or biological therapy.
Palliative radiotherapy may be permitted for symptomatic control of pain from bone
metastases in extremities, provided that the radiotherapy does not involve target
lesions, and the reason for the radiotherapy does not reflect progressive disease.
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. Relapse within six months after adjuvant chemotherapy (treatment-free interval < 182
days).
9. 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.
10. Active infection or other serious underlying medical condition, which might prevent
the patient from receiving treatment or to be followed.
11. Evidence of significant medical illness, abnormal laboratory finding or psychiatric
illness/social situation that would, in the Investigator's judgement, make the patient
inappropriate for this study.
12. Known contraindications to VEGF directed therapy Target Disease Exceptions
13. Known uncontrolled hypersensitivity to the investigational drugs.
14. History of major thromboembolic event defined as:
- Uncontrolled pulmonary embolism (PE)
- Deep venous thrombosis (DVT)
- Other related conditions, though patients with stable therapeutic anticoagulation
for more than three months prior randomization are eligible for this study.
15. History of a cerebral vascular accident, transient ischemic attack or subarachnoid
haemorrhage within the past 3 months.
16. History of clinically significant haemorrhage in the past 3 months.
17. Radiotherapy to the target lesion within the past 3 months prior to baseline imaging
18. Persistant grade 3 or 4 toxicity from previous chemotherapy and/or radiotherapy,
except alopecia. Patients with ongoing ≥ Grade 2 neuropathy are to be excluded.
19. Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with
radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone
therapy will be allowed if administered as stable dose for at least one month before
randomisation).
20. Leptomeningeal disease
21. Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina,
history of infarction within the past 12 months prior to start of study treatment,
congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion)
See Appendix 12.
22. 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.
23. Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent
major blood vessels.
24. Active or chronic hepatitis C and/or B infection
25. Known hypersensitivity to the trial drugs, or to their excipients.
26. Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug
27. 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
NCT02730416
Organization ID
ENGOT-EN1/FANDANGO
Responsible Party
Sponsor
Study Sponsor
Nordic Society of Gynaecological Oncology - Clinical Trials Unit
Collaborators
North Eastern German Society of Gynaecological Oncology
Study Sponsor
Mansoor R Mirza, MD, Study Chair, NSGO
Verification Date
October 2019