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

Study Overview
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Brief Summary
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The primary objective of this study is to estimate the Progression Free Survival Rates (PFS) of patients with relapsed ovarian cancer after 9 months of continuous treatment with either BIBF 1120 or matching placebo.

Official Title
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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

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Drug: BIBF1120
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients with histologically confirmed advanced ovarian carcinoma, fallopian tube carcinoma or primary peritoneal cancer of serous type with recurrent disease and who responded to 2nd, 3rd or 4th line chemotherapy. Response is defined as either a confirmed decline in CA125 of at least 50% from the pre-treatment value or an Objective Response, i.e. a Partial Response (PR) or Complete Response (CR) according to the RECIST criteria in patients with measurable disease. Treatment-free interval of < 12 months since commencing prior treatment regimen for relapsed ovarian cancer. Full recovery from all therapy related toxicities of previous chemotherapy and or radiotherapy or recovery in as much as no further improvement may be expected by the investigator. Age > 18 years. Life expectancy of at least 3 months. ECOG Performance Score < 2. Adequate hepatic function: total bilirubin 26µmol/L, ALT and/or AST 1.5x upper limit of normal (ULN). INR, Prothrombin time (PT) and partial thromboplastin time (PTT): maximum 50% deviation from normal limits. Adequate renal function: serum creatinine 1.5 x ULN. Absolute neutrophil count (ANC) >1.5 x 109l, Platelets > 100 x 109/l, Haemoglobin > 9.0 g/dl. Written informed consent consistent with ICH-GCP guidelines. Minimum time elapsed since last chemotherapy (including hormonal treatment other than Hormone Replacement Therapy [HRT]) or immunotherapy and the first administration of BIBF 1120 must be more than 4 but less than 8 weeks. Exclusion Criteria: Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study. Major injuries and/or surgery within past 4 weeks with incomplete wound healing or bone fracture and planned surgical procedures during the study period. Hypersensitivity to BIBF 1120 or the excipients of the study drug. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure > NYHA II). History of haemorrhagic or thrombotic event in the past 12 months. Known inherited predisposition to bleeds or to thrombosis. Patients who require full-dose anticoagulation. Gastrointestinal disorders or abnormalities that would inhibit absorption of the study drug. Brain metastases or leptomeningeal disease. Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial. Chemo-, radio-, or immunotherapy within the past four weeks prior to treatment with the trial drug. Patients unable to comply with the protocol. Active alcohol or drug abuse. Other documented malignancy with the exception of non-melanomatous skin cancer within the past 5 years. Patients who are not clinically sterile.

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: Prevention
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBF1120<br> | Drug: BIBF1120<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS Rate at 36 Weeks (After 9 Months) | 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. | 36 weeks (after 9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS Rate at 12 Weeks (After 3 Months) and 24 Weeks ( After 6 Months) | 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. | 12 weeks (after 3 months) and 24 weeks ( after 6 months) | 
| Time to Tumour Progression | 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. | 9 months | 
| Time to Death | This end point was not determined as no patients died during the trial. | 9 months | 
| Incidence and Intensity of Adverse Events With Grading According CTCAE | Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0). | First drug administration until 28 days after last drug administration,up until 309 days | 
| Clinical Relevant Abnormalities for Laboratory Parameters | Clinical Relevant Abnormalities for laboratory parameters. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Events. | First drug administration until 28 days after last drug administration, up until 309 days |