Phase 2 Study of G-202 in Patients With Chemotherapy-Naïve Metastatic Castrate-Resistant Prostate Cancer

• Status: Withdrawn
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: Male

Summary

Prostate cancer that has returned after local treatment usually responds to hormone blocking treatment, but most patients eventually experience disease progression. Further chemotherapy does not normally lead to a cure or dramatic improvement in the disease and there is a need to identify new drugs that are beneficial for these patients without unacceptable side effects. Prodrug chemotherapy is an approach in which an inactive non-toxic agent is administered to the patient and gets activated within the body at specific locations, resulting in a higher concentration of the cytotoxic form at a tumour location whilst avoiding general side effects. G-202 is an example of prodrug chemotherapy. It does not have many general side effects because it is converted to a cell toxin only at the tumour or other specific locations in the body. G-202 is activated by Prostate Specific Memory Antigen (PSMA), a substance expressed by prostate cancer cells and in the blood vessels of most solid tumours, but not by normal cells or blood vessels in normal tissue. It is believed that activation of the prodrug G-202 will allow the drug to kill cancer cells, particularly prostate cancer cells. This study will evaluate the activity and safety of G-202 in men with castration-resistant prostate cancer (CRPC), which means the cancer has progressed after hormone blocking treatment, but who have not yet received chemotherapy and who have no or only a few symptoms from their CRPC. The study will evaluate clinical activity and safety of G-202 administered on three consecutive days of a 28-day cycle.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GenSpera, Inc.

Criteria

Inclusion Criteria:

• Confirmed prostate adenocarcinoma

• Asymptomatic or minimally symptomatic

• Radiographic metastatic or recurrent disease

• Chemically- or surgically-castrated with disease progression

• Castrate testosterone level <50 ng/dL

• Discontinued flutamide, bicalutamide and nilutamide

• Absence of known brain metastases

• Age ≥18 years

• Eastern Cooperative Oncology Group performance status ≤ 2

• Estimated life expectancy ≥ 6 months

• Adequate hematopoietic function as demonstrated by:

• hemoglobin of ≥ 9.0 g/dL without need for sustained blood transfusions

• platelet count ≥100,000 platelet/mm3 (100 x 109/L)

• White Blood Cell (WBC) count ≥ 2.0 x109/L and Absolute Neutrophil Count (ANC) ≥1.5 x109/L

• Adequate hepatobiliary function as demonstrated by:

• Total bilirubin level ≤1.5 times the upper limit of normal (ULN), unless the patient has Gilbert's syndrome in which case the patient must have a total bilirubin level ≤ 2.5 x ULN

• alanine aminotransferase (ALT) levels ≤ 2.5 x ULN

• Adequate renal function as demonstrated by creatinine level ≤1.5 x ULN or creatinine clearance (measured or calculated by Cockcroft-Gault formula) ≥ 50mL/min

• Acceptable coagulation profile (PT or INR, PTT < 1.5 x ULN)

• If of reproductive capacity, willing to use an effective double barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc) during the study and for 30 days after the last administration of G-202

Exclusion Criteria:

• Prior chemotherapy

• Other concurrent therapy for prostate cancer other than LHRH agonists or antagonists.

• Treatment with therapeutic radionucleotides within 12 weeks of study entry

• Radiation therapy < 4 weeks before study entry

• Documentation of keratosis follicularis

• Pre-existing cardiac condition:

• use of inhibitors or inducers of cytochrome (CYP3A4) iso-enzymes

• Chronic use of opioids for cancer-related pain

• Corrected QT interval > 470 msec

• Active uncontrolled infection, including known history of AIDS, hepatitis B or C

• Proteinuria level > +2 on urine analysis