A Phase I/II Study of HE3235 in Patients With Prostate Cancer

• To evaluate the safety and tolerance of HE3235 when administered orally to prostate cancer patients in 28 day cycles. [ Time Frame: Treatment period ] [ Designated as safety issue: Yes ]
• To evaluate the pharmacokinetic profiles of HE3235 and major metabolites at different dose levels after 28 days of dosing. [ Time Frame: Treatment period ] [ Designated as safety issue: No ]
• To assess potential activity of HE3235 in prostate cancer patients. [ Time Frame: Treatment period and post-study follow-up period ] [ Designated as safety issue: No ]

• Explore circulating tumor cell (CTC) enumeration in response to treatment as a marker evaluating whether an investigational therapy is effective for tumor treatment [ Time Frame: Treatment period ] [ Designated as safety issue: No ]
• Evaluate the role of molecular profiling of CTC in predicting sensitivity to treatment and treatment response. [ Time Frame: Treament period and post-study follow-up ] [ Designated as safety issue: No ]

This is a phase I/II, open-label, dose escalation study of HE3235 administered orally to patients with advanced prostate cancer who have failed hormone therapy and at least one taxane based chemotherapy regimen.

Main Inclusion Criteria:

• Patient is male and at least 18 years of age, at the time of screening;
• Patient has metastatic disease (any T, any N, M1);
• Patient has failed at least 1 taxane regimen; or Patient has symptomatic or asymptomatic CRPC and is chemotherapy-naïve
• Patient has histologically or cytologically confirmed adenocarcinoma of the prostate;

• Patient has progression of disease despite adequate hormone therapy, demonstrated by one of the following:

  • PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions, at least 1 week apart.
  • Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria;
  • Progression of metastatic bone disease on bone scan with > 2 new lesions
• Patient has ECOG (Eastern Cooperative Oncology Group) performance status of 0-2;

Main Exclusion Criteria:

• Patient has symptomatic parenchymal brain metastases or active epidural disease requiring whole-brain irradiation Treated epidural disease is allowed
• Patient has active infection;
• Patient having a history of clinically significant cardiovascular disease (such as CHF), clinically significant hepatic, respiratory or renal abnormalities;
• Patient who has any clinically significant abnormalities in laboratory results at screening
• Patient who has a history of clinically significant neurological or psychiatric condition;

Additional criteria are applicable to expansion cohorts.