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

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

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

Study Overview

• Status: Completed
• Conditions: Genital Neoplasms, Female
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Drug: BIBF 1120

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Therapy	Drug: Carboplatin; Drug: Paclitaxel; Drug: BIBF 1120
Experimental: Monotherapy	Drug: BIBF 1120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: July 2, 2014
• First Submitted That Met QC Criteria: July 2, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Nintedanib
• Other Study ID Numbers: 1199.6