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
Condition: Prostatic Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: BIBF 1120; BIBW 2992; Sequential BIBF 1120 + BIBW 2992
Intervention MeSH terms: Nintedanib; Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Enrollment: 87.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

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 For a patient who has withdrawn from anti-androgen therapy less than 6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.