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A Randomised Placebo-Controlled Phase II Study of Continuous Maintenance Treatment With BIBF 1120 Following Chemotherapy in Patients With Relapsed Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT00710762
Recruitment Status : Completed
First Posted : July 4, 2008
Results First Posted : December 4, 2014
Last Update Posted : August 15, 2016
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Intervention Model: Parallel Assignment;   Primary Purpose: Prevention
Condition Ovarian Neoplasms
Interventions Drug: BIBF1120
Drug: Placebo
Enrollment 89
Recruitment Details  
Pre-assignment Details 89 patients were enrolled and 84 patients were randomised for this study.
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description Patients were treated with 250mg nintedanib twice daily Patients were treated with matching placebo twice daily
Period Title: Overall Study
Started 44 40
Completed 5 0
Not Completed 39 40
Reason Not Completed
Progressive disease             27             30
Adverse Event other disease worsening             2             1
Other Adverse Event             7             7
Lost to Follow-up             1             0
Reason other than listed above             2             2
Arm/Group Title Nintedanib Placebo Total
Hide Arm/Group Description Patients were treated with 250mg nintedanib twice daily Patients were treated with matching placebo twice daily Total of all reporting groups
Overall Number of Baseline Participants 43 40 83
Hide Baseline Analysis Population Description
Treated set consist of all patients who received at least 1 dose of nintedanib or placebo. Note: 43 patients were included in the analyses instead of 44 patients in nintedanib arm as one patient was excluded after drug administration due to important protocol violation.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 43 participants 40 participants 83 participants
58.4  (9.5) 61.3  (9.1) 59.8  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 40 participants 83 participants
Female
43
 100.0%
40
 100.0%
83
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title PFS Rate at 36 Weeks (After 9 Months)
Hide Description The rate (probability) of being progression free at Week 36. Progression Free Survival (PFS) was defined according to RECIST version 1.0 from the time of first study drug administration to the first time of either objective tumour progression, the appearance of ≥1 new tumour lesion(s), occurrence or significant progression of malignant ascites, tumour related death, or the time when patients were censored at last known follow up. The rate is the Kaplan-Meier estimated percent probability.
Time Frame 36 weeks (after 9 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set.
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description:
Patients were treated with 250mg nintedanib twice daily
Patients were treated with matching placebo twice daily
Overall Number of Participants Analyzed 43 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability of PFS
15.6
(3.8 to 27.3)
2.9
(0.0 to 8.4)
2.Secondary Outcome
Title PFS Rate at 12 Weeks (After 3 Months) and 24 Weeks ( After 6 Months)
Hide Description The rate (probability) of being progression free at Week 12 and Week 24. Progression Free Survival (PFS) was defined according to RECIST version 1.0 from the time of first study drug administration to the first time of either objective tumour progression, the appearance of ≥1 new tumour lesion(s), occurrence or significant progression of malignant ascites, tumour related death, or the time when patients were censored at last known follow up. The rate is the Kaplan-Meier estimated percent probability.
Time Frame 12 weeks (after 3 months) and 24 weeks ( after 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description:
Patients were treated with 250mg nintedanib twice daily
Patients were treated with matching placebo twice daily
Overall Number of Participants Analyzed 43 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability of PFS
at 24 weeks ( after 6 months)
26.7
(12.5 to 40.8)
17.3
(5.2 to 29.4)
at 12 weeks (after 3 months)
45.3
(29.5 to 61.2)
46.2
(30.5 to 61.8)
3.Secondary Outcome
Title Time to Tumour Progression
Hide Description

Time to Tumour Progression according to RECIST version 1.0 , CA-125 (ovarian tumour marker) levels and RECIST + CA-125 levels.

For CA-125, progressive disease was defined on the basis of progressive serial elevations of CA-125 according to the following criteria:

Patients with elevated CA-125 pre-treatment and normalisation of CA-125 had to show evidence of CA-125 levels ≥2 x ULN on 2 occasions at least 1 week apart. or Patients with elevated CA-125 pre-treatment that never normalised had to show evidence of CA-125 levels ≥2 x the nadir value on 2 occasions at least 1 week apart. or Patients with CA-125 in the normal range pre-treatment had to show evidence of CA-125 levels ≥2 x ULN on 2 occasions at least 1 week apart.

Composite (RECIST+CA-125) endpoint is the RECIST progressive disease (PD) if it occurred or the CA-125 PD if it occurred in the absence of RECIST PD.

Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description:
Patients were treated with 250mg nintedanib twice daily
Patients were treated with matching placebo twice daily
Overall Number of Participants Analyzed 43 40
Median (95% Confidence Interval)
Unit of Measure: days
according to RECIST and CA-125
83.00
(78.0 to 149.0)
84.00
(78.0 to 87.0)
according to CA-125
85.00
(79.0 to 149.0)
86.00
(67.0 to 113.0)
according to RECIST
143.0
(82.0 to 175.0)
85.0
(78.0 to 89.0)
4.Secondary Outcome
Title Time to Death
Hide Description This end point was not determined as no patients died during the trial.
Time Frame 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint could not be calculated as no patients died.
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description:
Patients were treated with 250mg nintedanib twice daily
Patients were treated with matching placebo twice daily
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Incidence and Intensity of Adverse Events With Grading According CTCAE
Hide Description Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
Time Frame First drug administration until 28 days after last drug administration,up until 309 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description:
Patients were treated with 250mg nintedanib twice daily
Patients were treated with matching placebo twice daily
Overall Number of Participants Analyzed 43 40
Measure Type: Number
Unit of Measure: percentage of participants
CTCAE grade 1 2.3 25.0
CTCAE grade 2 34.9 42.5
CTCAE grade 3 53.5 25.0
CTCAE grade 4 7.0 2.5
CTCAE grade 5 0.0 0.0
6.Secondary Outcome
Title Clinical Relevant Abnormalities for Laboratory Parameters
Hide Description Clinical Relevant Abnormalities for laboratory parameters. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Events.
Time Frame First drug administration until 28 days after last drug administration, up until 309 days
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description:
Patients were treated with 250mg nintedanib twice daily
Patients were treated with matching placebo twice daily
Overall Number of Participants Analyzed 43 40
Measure Type: Number
Unit of Measure: Percentage of participants
Alanine aminotransferase increased 37.2 7.5
Gamma-glutamyltransferase increased 30.2 2.5
Aspartate aminotransferase increased 25.6 2.5
Blood alkaline phosphatase increased 7.0 5.0
Blood lactate dehydrogenase increased 4.7 0.0
Blood alkaline phosphatase 0.0 2.5
Blood alkaline phosphatase abnormal 2.3 2.5
Lymphocyte count decreased 0.0 2.5
Vitamin B12 decreased 0.0 2.5
Alanine aminotransferase abnormal 2.3 0.0
Blood lactate dehydrogenase abnormal 2.3 0.0
Gamma-glutamyltransferase abnormal 2.3 0.0
Neutrophil count decreased 2.3 0.0
White blood cells urine positive 2.3 0.0
Blood pressure increased 0.0 2.5
Electrocardiogram T wave amplitude decreased 0.0 2.5
Liver function test abnormal 2.3 0.0
Time Frame First drug administration until 28 days after last drug administration, up until 309 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description Patients were treated with 250mg nintedanib twice daily. Patients were treated with matching placebo twice daily.
All-Cause Mortality
Nintedanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Nintedanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   14/43 (32.56%)   10/40 (25.00%) 
Blood and lymphatic system disorders     
Pancytopenia  1  0/43 (0.00%)  1/40 (2.50%) 
Gastrointestinal disorders     
Abdominal distension  1  1/43 (2.33%)  0/40 (0.00%) 
Abdominal pain  1  4/43 (9.30%)  2/40 (5.00%) 
Ascites  1  6/43 (13.95%)  5/40 (12.50%) 
Constipation  1  1/43 (2.33%)  0/40 (0.00%) 
Diarrhoea  1  3/43 (6.98%)  0/40 (0.00%) 
Intestinal obstruction  1  2/43 (4.65%)  1/40 (2.50%) 
Nausea  1  1/43 (2.33%)  0/40 (0.00%) 
Rectal haemorrhage  1  1/43 (2.33%)  0/40 (0.00%) 
Small intestinal obstruction  1  1/43 (2.33%)  1/40 (2.50%) 
Vomiting  1  10/43 (23.26%)  0/40 (0.00%) 
General disorders     
Pyrexia  1  1/43 (2.33%)  0/40 (0.00%) 
Infections and infestations     
Catheter related infection  1  0/43 (0.00%)  1/40 (2.50%) 
Lower respiratory tract infection  1  1/43 (2.33%)  0/40 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  1/43 (2.33%)  0/40 (0.00%) 
Aspartate aminotransferase increased  1  1/43 (2.33%)  0/40 (0.00%) 
Blood alkaline phosphatase increased  1  1/43 (2.33%)  0/40 (0.00%) 
Gamma-glutamyltransferase increased  1  1/43 (2.33%)  0/40 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  1/43 (2.33%)  0/40 (0.00%) 
Dehydration  1  0/43 (0.00%)  1/40 (2.50%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lung neoplasm  1  0/43 (0.00%)  1/40 (2.50%) 
Neuroendocrine tumour  1  0/43 (0.00%)  1/40 (2.50%) 
Psychiatric disorders     
Abnormal behaviour  1  1/43 (2.33%)  0/40 (0.00%) 
Agitation  1  1/43 (2.33%)  0/40 (0.00%) 
Confusional state  1  1/43 (2.33%)  0/40 (0.00%) 
Delusion  1  1/43 (2.33%)  0/40 (0.00%) 
Depression  1  0/43 (0.00%)  1/40 (2.50%) 
Mood altered  1  0/43 (0.00%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders     
Pleuritic pain  1  1/43 (2.33%)  0/40 (0.00%) 
Pulmonary embolism  1  0/43 (0.00%)  1/40 (2.50%) 
Vascular disorders     
Deep vein thrombosis  1  1/43 (2.33%)  0/40 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nintedanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   42/43 (97.67%)   37/40 (92.50%) 
Ear and labyrinth disorders     
Tinnitus  1  3/43 (6.98%)  1/40 (2.50%) 
Gastrointestinal disorders     
Abdominal distension  1  3/43 (6.98%)  1/40 (2.50%) 
Abdominal pain  1  23/43 (53.49%)  15/40 (37.50%) 
Constipation  1  9/43 (20.93%)  11/40 (27.50%) 
Diarrhoea  1  33/43 (76.74%)  14/40 (35.00%) 
Dyspepsia  1  3/43 (6.98%)  1/40 (2.50%) 
Flatulence  1  5/43 (11.63%)  4/40 (10.00%) 
Nausea  1  32/43 (74.42%)  13/40 (32.50%) 
Rectal haemorrhage  1  3/43 (6.98%)  1/40 (2.50%) 
Stomatitis  1  5/43 (11.63%)  1/40 (2.50%) 
Vomiting  1  23/43 (53.49%)  9/40 (22.50%) 
General disorders     
Fatigue  1  12/43 (27.91%)  11/40 (27.50%) 
Oedema peripheral  1  1/43 (2.33%)  3/40 (7.50%) 
Infections and infestations     
Infection  1  3/43 (6.98%)  1/40 (2.50%) 
Nasopharyngitis  1  6/43 (13.95%)  2/40 (5.00%) 
Upper respiratory tract infection  1  4/43 (9.30%)  3/40 (7.50%) 
Urinary tract infection  1  4/43 (9.30%)  4/40 (10.00%) 
Investigations     
Alanine aminotransferase increased  1  16/43 (37.21%)  3/40 (7.50%) 
Aspartate aminotransferase increased  1  10/43 (23.26%)  1/40 (2.50%) 
Gamma-glutamyltransferase increased  1  12/43 (27.91%)  1/40 (2.50%) 
Metabolism and nutrition disorders     
Anorexia  1  11/43 (25.58%)  6/40 (15.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/43 (11.63%)  6/40 (15.00%) 
Back pain  1  2/43 (4.65%)  8/40 (20.00%) 
Muscle spasms  1  2/43 (4.65%)  4/40 (10.00%) 
Pain in extremity  1  4/43 (9.30%)  2/40 (5.00%) 
Nervous system disorders     
Dizziness  1  4/43 (9.30%)  4/40 (10.00%) 
Headache  1  6/43 (13.95%)  4/40 (10.00%) 
Lethargy  1  4/43 (9.30%)  4/40 (10.00%) 
Neuropathy peripheral  1  0/43 (0.00%)  3/40 (7.50%) 
Paraesthesia  1  1/43 (2.33%)  4/40 (10.00%) 
Psychiatric disorders     
Anxiety  1  2/43 (4.65%)  4/40 (10.00%) 
Insomnia  1  0/43 (0.00%)  3/40 (7.50%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  6/43 (13.95%)  1/40 (2.50%) 
Dyspnoea  1  5/43 (11.63%)  3/40 (7.50%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  2/43 (4.65%)  4/40 (10.00%) 
Pruritus  1  0/43 (0.00%)  6/40 (15.00%) 
Rash  1  3/43 (6.98%)  5/40 (12.50%) 
Vascular disorders     
Hot flush  1  3/43 (6.98%)  3/40 (7.50%) 
Hypertension  1  5/43 (11.63%)  2/40 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 11.1
Data from all randomised patients collected upto NOV’08 were included in all above sections,unless stated otherwise.5 patients continued on BIBF1120 after database lock(DBL)-NOV’08 upto Mar’14,but due to limited data no further analyses were done.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI’s intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00710762     History of Changes
Obsolete Identifiers: NCT00370175
Other Study ID Numbers: 1199.9
EUDRACT2005-002427-14
First Submitted: July 3, 2008
First Posted: July 4, 2008
Results First Submitted: November 14, 2014
Results First Posted: December 4, 2014
Last Update Posted: August 15, 2016