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

Boehringer Ingelheim9 sites in 1 country87 target enrollmentMarch 2006

ConditionsProstatic Neoplasms

DrugsBIBF 1120 BIBW 2992 Sequential BIBF 1120 + BIBW 2992

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Prostatic Neoplasms
Sponsor: Boehringer Ingelheim
Enrollment: 87
Locations: 9
Primary Endpoint: Progression Free Rate (PFR) at 12 Weeks
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

March 2006

End Date

December 2008

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Male

Investigators

Sponsor

Boehringer Ingelheim

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 For a patient who has withdrawn from anti-androgen therapy less than 6 months prior to inclusion in trial one of the following criteria is also required: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.

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.

Outcomes

Primary Outcomes

Progression Free Rate (PFR) at 12 Weeks

Time Frame: 12 weeks

PFR is defined as a composite endpoint for disease progression. If patients met one of the following criteria they were counted as having progressive disease (PD): * Prostate serum antigen (PSA) progression according to Prostate-Specific Antigen Working Group (PSAWG) criteria * Bone metastasis progression- development of new lesions on bone scan or development of disease-related skeletal related events (SREs) * Disease progression according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0

Secondary Outcomes

Progression Free Rate at 24 and 48 Weeks(24 weeks and 48 weeks)
Incidence and Worst Intensity of Adverse Events With Grading According CTCAE(from first intake of treatment until 29 days after last intake of treatment (Up to 52 weeks))
Number of Patients Showing Prostate Serum Antigen (PSA) Response(End of trial visit, 29 ± 1 days after Day 1 of the last treatment cycle (Up to 48 weeks))
RECIST Tumour Progression Rate at 12, 24, 36, and 48 Weeks(12, 24, 36, and 48 weeks)
Duration of PSA Response(End of trial visit, 29 ± 1 days after Day 1 of the last treatment cycle (Up to 48 weeks))
Changes in Safety Laboratory Parameters(from first intake of treatment until 29 days after last intake of treatment (Up to 52 weeks))
Trough Plasma Concentrations for BIBF 1120 and BIBW 2992 for the Combination Therapy(Day7, Day 14)
Time to PSA Progression(Start of treatment until end of treatment (Up to 48 weeks))
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(12, 24, 36 and 48 weeks)
Duration of RECIST Response(Up to 48 weeks)
Overall Survival (Time to Death)(start of treatment until 28 days after end of treatment (Up to 52 weeks))
Time to Progression(start of treatment until end of the treatment (Up to 48 weeks))
Trough Plasma Concentrations for BIBF 1120 and BIBW 2992 for the Monotherapy(Day 15, Day 29 and Day 57)