Efficacy Study of ABR-215050 to Treat Prostate Cancer

Phase II Randomized Double Blind Placebo-Controlled Study to Determine the Efficacy of ABR-215050 in Asymptomatic Patients With Metastatic Castrate-Resistant Prostate Cancer

To investigate ABR-215050 as a possible treatment for prostate cancer.

For asymptomatic patients with Castrate-Resistant Prostate Cancer (CRPC), a "window of opportunity" is present. During this "window of opportunity" an intervention with little or no toxicity and the potential for extending the "symptom-free" period would be of great value to keep metastatic patients in an asymptomatic stage and thus delay the introduction of chemotherapy. The purpose of this study is to evaluate the safety and efficacy of ABR-215050 as an interventional agent for this role.

Overall survival for patients participating in study 07TASQ08 will be evaluated retrospectively using a separate study protocol 11TASQ11.

Inclusion criteria:

• Histologically confirmed diagnosis of adenocarcinoma of the prostate

• Asymptomatic metastatic CRPC (VAS pain score less than or equal to 3). The patient may take non-opioid analgesics for non-cancer pain discomfort

• Evidence of metastatic disease from CT or Bone scan

• Evidence of progressive disease after castration levels of testosterone have been achieved defined by any of the following criteria:

  • Increased serum prostate-specific antigen (PSA) levels (Confirmed by 3 consecutive PSA measurements within 1 year with at least 14 days between each measurement)
  • Progression of bidimensionally measurable soft tissue (nodal) metastasis: (CT scan or MRI)
  • Progression of bone disease: (New bone lesions by bone scan within the past 12 weeks)

• Castrate levels of serum testosterone (less than or equal to 50 ng/dL or 1.7 nmol/L. Testosterone levels will not be required for patients who have had bilateral orchiectomy)

• Karnofsky score 70-100

• Laboratory values as follows:

  • Hb greater than or equal to 90g/L (greater than or equal to 9g/dL)
  • Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN)
  • Total bilirubin less than or equal to 1.5 x ULN
  • AST (SGOT) / ALT (SGPT) less than or equal to 2.5 x ULN
  • Serum amylase less than or equal to ULN. (If serum amylase is greater than ULN, pancreatic amylase and serum lipase should be analyzed. If both pancreatic amylase and serum lipase is greater than ULN, exclude patient)

• Patient if sexually active with partner of child bearing potential will agree to use adequate contraceptive methods (barrier contraceptive with spermicide or vasectomy) while on study drug

• No evidence (greater than or equal to 5 years) of prior malignancies (except successfully treated basal cell, squamous cell carcinoma of the skin)

• Ability to administer and retain oral medication

• Able to adhere to the study visit schedule and other protocol requirements

Exclusion criteria:

• Prior cytotoxic chemotherapy within 3 years
• Previous anti-cancer therapy using biologics or vaccines within the last 6 months. Previous treatment with bevacizumab is not allowed.
• Any treatment modalities, involving radiation and surgery, not discontinued at least 4 weeks prior to treatment in this study
• Myocardial infarction or any acute coronary syndrome within one year or current uncontrolled arrhythmias, symptomatic uncontrolled congestive heart failure, unstable angina pectoris, uncontrolled hypertension
• History of pancreatitis
• Any condition, including the presence of laboratory abnormalities, which confounds the ability to interpret data from the study or places the patient at unacceptable risk if he participates in the study
• Concurrent use of other anti-cancer agents or treatments [a stable dose of LHRH agonists, bicalutamide (e.g. Casodex) and/or other antiandrogens is allowed]
• Known brain metastases
• Simultaneous participation in any other study involving investigational drugs or having participated in a study less than 4 weeks prior to start of study treatment
• Concomitant systemic treatment with warfarin and/or corticosteroids corresponding to a prednisolone dose above 5 mg/day
• Exposure to ketoconazole or other strong CYP3A4 inhibitors or inducers intravenously or orally within 14 days prior to inclusion
• Known positive serology for HIV (patients with known history of HIV will be excluded because of potential for unforeseen toxicity and morbidity in an immunocompromised host)
• Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of a chronic virus hepatitis or known viral hepatitis carrier (patients recovered from hepatitis will be allowed to enter the study)