Clinical trial NCT00706628: A Multi-centre 3-arm Randomised Phase II Trial of BIBF 1120 Versus BIBW 2992 Versus Sequential Administration of BIBF 1120 and BIBW 2992 in Patients With Hormone-resistant Prostate Cancer
Official title: A Multi-centre 3-arm Randomised Phase II Trial of BIBF 1120 Versus BIBW 2992 Versus Sequential Administration of BIBF 1120 and BIBW 2992 in Patients With Hormone-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostatic Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-06-27
Enrollment: 87
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this trial is to estimate and compare the 12-week progression-free rate of BIBF 1120, BIBW 2992 or sequential administration of BIBF 1120 and BIBW 2992 in patients with HRPC as determined by radiographic, bone and PSA criteria.


Eligibility criteria: Inclusion Criteria:

* Age \>18 years.
* Signed informed consent.
* Able to comply with protocol requirements.
* Histologically, cytologically or biochemically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as documented by progression following at least one hormonal therapy, which must include orchidectomy or gonadotropin releasing hormone agonist (GnRHa).
* Progressive Disease (PD) is defined as a minimum of three consecutive serum PSA measurements obtained at least 7 days apart within the previous 3 months of start of trial, which document progressively increasing values. Patients with progression of measurable disease (RECIST) or progression of bone disease must also fit the criterion for PSA progression.
* Patients must have documented progression (as defined above) following anti-androgen withdrawal of 4 weeks duration for flutamide and 6 weeks for bicalutamide or nilutamide. For a patient who has withdrawn from anti-androgen therapy less than 6 months prior to inclusion in trial one of the following criteria is also required:
* Following the completion of the anti-androgen withdrawal period one PSA higher than the last pre-withdrawal PSA.
* Or Following the completion of the anti-androgen withdrawal period if the PSA value has decreased, he can still qualify if 2 increases in PSA are documented after the post- withdrawal nadir.
* PSA \> 5ng/mL.
* Life expectancy of at least 12 weeks.
* ECOG performance status 0-1 (see appendix 11.2).
* Stable analgesia requirements.
* Adequate hepatic function: total bilirubin \< 26µmol/L, ALT and/or AST \< 1.5x upper limit of normal (ULN).
* Adequate renal function: serum creatinine \< 1.5 x ULN.
* INR Prothrombin time (PT) and partial thromboplastin time (PTT) \<1.5 upper limit of normal.
* Absolute neutrophil count (ANC) \> 1.5 x 109l, Platelets \> 100 x 109/l.
* Haemoglobin \> 9.0 g/dl.
* LVEF \> 50 % on MUGA scan or echocardiogram.
* Castrate testosterone level \[\< 20ng/dl or \<0.69nM (nM/L x 28.8 = ng/dl)\], which must be maintained during the duration of the trial by orchidectomy or medical castration.
* Patient on oral or intravenous bisphosphonates are allowed to enter the trial as long as they have been on bisphosphonates for a minimum of 3 months.

Exclusion Criteria:

* Prior treatment with inhibitors of EGFR, HER 2 and/or VEGF receptors.
* Prior treatment with cytotoxic chemotherapy.
* Known hypersensitivity to the trial drugs or their excipients.
* Systemic corticosteroids 28 days before screening (inhaled corticosteroids prescribed for bronchospasm are allowed). Patients on long-term stable-dose steroids for concurrent illness are not excluded.
* Treatment with any investigational drug within 28 days of trial onset.
* History of other malignancies which could affect compliance with the protocol or interpretation of results within 5-years. Patients with adequately treated basal or squamous cell skin cancer are generally eligible.
* 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 trial participation or trial drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the trial.
* Major injuries and/or surgery within 4 weeks of trial onset or bone fracture and planned surgical procedures during the trial period.
* Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 9 months, congestive heart failure \> NYHA II) (see appendix 11.5).
* History of haemorrhagic or thrombotic event in the past 12 months. Known inherited predisposition to bleeds or to thrombosis.
* Patient with history or clinical evidence of CNS disease or brain metastases.
* Patients with symptoms of impending or established spinal cord compression.
* Gastrointestinal disorders or abnormalities that would inhibit absorption of the trial drug.
* Patients who require full-dose anticoagulation.
* 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.

Primary outcomes:
measure: Progression Free Rate (PFR) at 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Progression Free Rate at 24 and 48 Weeks
timeFrame: 24 weeks and 48 weeks
measure: Number of Patients Showing Prostate Serum Antigen (PSA) Response
timeFrame: End of trial visit, 29 ± 1 days after Day 1 of the last treatment cycle (Up to 48 weeks)
measure: Duration of PSA Response
timeFrame: End of trial visit, 29 ± 1 days after Day 1 of the last treatment cycle (Up to 48 weeks)
measure: Time to PSA Progression
timeFrame: Start of treatment until end of treatment (Up to 48 weeks)
measure: RECIST Tumour Progression Rate at 12, 24, 36, and 48 Weeks
timeFrame: 12, 24, 36, and 48 weeks
measure: Overall Objective Response by RECIST Criteria (Version 1.0) (Complete Response [CR] or Partial Response [PR]) for Patients With Measurable Disease at 12, 24, 36 and 48 Weeks
timeFrame: 12, 24, 36 and 48 weeks
measure: Duration of RECIST Response
timeFrame: Up to 48 weeks
measure: Time to Progression
timeFrame: start of treatment until end of the treatment (Up to 48 weeks)
measure: Overall Survival (Time to Death)
timeFrame: start of treatment until 28 days after end of treatment (Up to 52 weeks)
measure: Incidence and Worst Intensity of Adverse Events With Grading According CTCAE
timeFrame: from first intake of treatment until 29 days after last intake of treatment (Up to 52 weeks)
measure: Changes in Safety Laboratory Parameters
timeFrame: from first intake of treatment until 29 days after last intake of treatment (Up to 52 weeks)
measure: Trough Plasma Concentrations for BIBF 1120 and BIBW 2992 for the Monotherapy
timeFrame: Day 15, Day 29 and Day 57
measure: Trough Plasma Concentrations for BIBF 1120 and BIBW 2992 for the Combination Therapy
timeFrame: Day7, Day 14
Other outcomes:
Locations:
city: Belfast
country: United Kingdom
facility: 1239.3.4402 Boehringer Ingelheim Investigational Site
city: Bournemouth
country: United Kingdom
facility: 1239.3.4406 Boehringer Ingelheim Investigational Site
city: Brighton
country: United Kingdom
facility: 1239.3.4408 Boehringer Ingelheim Investigational Site
city: Cheltenham
country: United Kingdom
facility: 1239.3.4409 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 1239.3.4405 Boehringer Ingelheim Investigational Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: 1239.3.4403 Boehringer Ingelheim Investigational Site
city: Southampton
country: United Kingdom
facility: 1239.3.4411 Boehringer Ingelheim Investigational Site
city: Sutton
country: United Kingdom
facility: 1239.3.4401 Boehringer Ingelheim Investigational Site
city: Truro
country: United Kingdom
facility: 1239.3.4410 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: