Dose Escalation Study of BIBF 1120 in Patients With Advanced Gynaecological Malignancies

Study Overview
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Brief Summary
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The primary objectives of this trial were to determine the safety, tolerability, and MTD of BIBF 1120 when added to standard therapy with carboplatin and paclitaxel

Official Title
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A Phase I Open Label Dose Escalation Study of Oral Treatment With BIBF 1120 in Combination With Standard Treatment of Paclitaxel and Carboplatin in Patients With Advanced Gynaecological Malignancies

Conditions
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Genital Neoplasms, Female

Intervention / Treatment
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* Drug: BIBF 1120
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with the following histologically confirmed advanced gynaecological malignancies: epithelial ovarian cancer, endometrial carcinoma, uterine sarcoma, mixed Müllerian tumour, fallopian tube carcinoma, primary peritoneal carcinoma, cervical carcinoma or vulvular carcinoma Metastatic disease or locally advanced disease that is not resectable with curative intention Indication for combination chemotherapy with paclitaxel/carboplatin as judged by the investigator Age 18 years or older Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Life expectancy of at least 6 months Written informed consent that is not consistent with ICH-GCP (International Conference on Harmonisation - Good Clinical Practice) guidelines and local requirements Exclusion Criteria: Participation in another clinical study within the past 4 weeks before start of therapy or concomitantly with this study Radiotherapy within 4 weeks before the start of therapy Chemotherapy, immunotherapy or hormonal therapy (with the exception of hormonal replacement therapy) within 4 weeks before the start of the therapy Patients with germ cell tumours, early stage ovarian cancer (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] stage I-IIA), primary cervical cancer (FIGO I-III), primary endometrial cancer (FIGO I-III) or borderline tumours Patients with known brain metastases Symptomatic bowel obstruction or known or suspected malabsorption Patients with pericardial effusion which is haemodynamically relevant Other malignancy diagnosed within the past 5 years (other than non-melanomatous skin cancer or cervical carcinoma in situ) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study medication History of haemorrhagic or thrombotic event (including transient ischemic attacks) in the past 6 months Concurrent therapeutic anticoagulation or anti-platelet therapy (except chronic low dose daily acetylsalicylic acid <300 mg) Major injuries and surgeries within the past 3 weeks, planned surgical procedures during the trial, incomplete wound healing Known hypersensitivity to paclitaxel, carboplatin, BIBF 1120 or any of their excipients or vehicles such as polyoxyethylated castor oil Clinically significant peripheral polyneuropathy (>CTCAE grade 1) which precludes therapy with paclitaxel Absolute neutrophil count (ANC) <1500/μL, platelet count <100000/μL, or haemoglobin <9 mg/dL Total bilirubin >1.5 mg/dL (26 μmol/L), ALT (Alanine aminotransferase) and/or AST (Aspartate aminotransferase) >1.5 x the upper limit of normal (ULN) Serum creatinine >1.5 mg/dL (>132 μmol/L) Persistent gross haematuria Pregnancy or breast feeding Women with childbearing potential and who are sexually active and unwilling to use a medically acceptable method of contraception (oral contraceptive, diaphragm with spermicide, intrauterine device, condom with spermicide) Known or suspected active drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy<br> | Drug: BIBF 1120<br> <br> Drug: Paclitaxel<br> <br> Drug: Carboplatin<br> <br> |
| Experimental: Monotherapy<br> | Drug: BIBF 1120<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of BIBF 1120 |  | up to 126 days | 
| Incidence and intensity of adverse events according to the CTCAE (Common terminology criteria for adverse events Version) version 3.0 with increasing doses of BIBF 1120 |  | up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumour response after treatment with BIBF 1120 in combination with carboplatin and paclitaxel in evaluable patients |  | up to 9 months | 
| Cancer antigen 125 (CA-125) response |  | Day 1 of each treatment period | 
| Time to tumour progression (time from treatment start to the time of documented tumour progression) |  | up to 9 months |