BGOG-cx1/ENGOT-cx1: "Randomized Double-blind Phase II Study Comparing 3-weekly Carboplatin + Paclitaxel With or Without Concomitant and Maintenance Nintedanib (NINTEDANIB) in Advanced or Recurrent Cervical Carcinoma."
Overview
- Phase
- Phase 2
- Intervention
- Nintedanib
- Conditions
- Uterine Cervical Neoplasms
- Sponsor
- Belgian Gynaecological Oncology Group
- Enrollment
- 120
- Locations
- 32
- Primary Endpoint
- Progression free survival
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Indication:
Treatment of subjects with advanced (FIGO stage IVB) or recurrent cervical cancer, prior radiochemotherapy or neo-adjuvant chemotherapy is allowed.
Study design:
This is a phase II randomized, double blind and placebo controlled trial evaluating the efficacy of Nintedanib/placebo in combination with the standard carboplatin and paclitaxel followed by Nintedanib/placebo maintenance in the treatment of patients with advanced or recurrent cervical cancer.
A total of 120 patients will be randomized between the experimental and control arm in a 1:1 ratio. Randomization will be stratified for 1previous chemotherapy for metastatic disease (yes/no) and 2disease status (Stage IVB primary versus recurrent disease).
Experimental arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and Nintedanib 200 mg BID followed by Nintedanib maintenance until progression or for a total maximum duration of 120 weeks.
Control arm: Subjects will receive 6 cycles of 3-weekly carboplatin (AUC 5) + paclitaxel (175 mg/m2) and placebo 200 mg BID followed by placebo maintenance until progression or for a total maximum duration of 120 weeks.
Subjects without evidence of disease progression after completion or discontinuation of the study treatment will be followed until radiographic disease progression, withdrawal of consent or death.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female subjects more than 18 years of age
- •Histologically or cytologically confirmed advanced (\[FIGO\] stage IVB), or recurrent/persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix will be eligible.
- •Prior treatment with angiogenesis inhibitors is allowed
- •Up to one prior line of chemotherapy for metastatic cervical cancer is allowed.
- •Treatment of primary disease with concomitant cisplatinum chemotherapy during radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
- •Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery is allowed and does not count as a line of chemotherapy for metastatic disease.
- •Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiochemotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
- •Treatment of primary disease with neoadjuvant chemotherapy before radical local surgery followed by adjuvant radiotherapy is allowed and does not count as a line of chemotherapy for metastatic disease.
- •Life expectancy at least 3 months.
- •ECOG Performance status score of 0 or 1
Exclusion Criteria
- •Known hypersensitivity to the trial drugs or to their excipients (including peanut or soya).
- •Brain or leptomeningeal metastases.
- •Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels.
- •Tumor infiltrating the mucosa of the bowel or bladder, or known fistulas between the tumor and the gastrointestinal or urinary tract.
- •Radiographic evidence of cavitary or necrotic tumours
- •Treatment with other investigational drugs or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with the trial.
- •Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic acid \<325 mg per day).
- •Major injuries within the past 4 weeks prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
- •History of clinically significant haemorrhagic or thromboembolic event in the past 6 months.
- •Known inherited predisposition to bleeding or thrombosis.
Arms & Interventions
Experimental arm
Nintedanib/vargatef
Intervention: Nintedanib
Comparator arm
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Progression free survival
Time Frame: 1.5 years after LPI
Primary objective: The purpose of this trial is to determine if chemotherapy (carboplatin/paclitaxel) plus Nintedanib (BIBF 1120) can improve progression free survival compared to chemotherapy (carboplatin/paclitaxel) plus placebo in patients with advanced or recurrent cervical cancer.
Secondary Outcomes
- Overall survival(5 years after LPI)
- Safety and toxicity(5 years after LPI)
- Patient health status(5 years after LPI)