A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: TH-302
Intervention description: 480 mg/m2 by iv infusion over 30 - 60 min on Days 1, 8, and 15 of a 28-day cycle.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: TH-302; Advanced Melanoma; Metastatic; Biomarker; Mucosal Melanoma; Evofosfamide

Summary:

      The primary objective of this study is to determine the response rate, duration of
      response,progression-free survival and overall survival of subjects with advanced melanoma
      treated with TH-302.
    

Eligibility criteria:

        Inclusion Criteria:

          1. At least 18 years of age

          2. Ability to understand the purposes and risks of the study and has signed a written
             informed consent form approved by the investigator's Regional Ethics Board/Independent
             Ethics Committee (REB/IEC)

          3. Histologically documented cutaneous or mucosal malignant melanoma, which is recurrent
             or metastatic and is not curable by surgical or other means.

          4. Adequate tumour tissue (greater than 0.5cm3 preferred, 3 X core biopsy acceptable)
             available and agreement from subjects that this tissue from their primary and/or
             metastatic tumour be made available for assessment of potential biomarkers.

          5. Ability and availability to complete all prescribed biomarker studies (Screening and
             after Cycle 2).

          6. Recovered to Grade 1 from reversible toxicities of prior therapy

          7. Presence of clinically and/or radiologically documented disease. At least one site of
             disease (which will not be removed during the course of the study) must be
             uni-dimensionally measurable as per RECIST 1.1 or clinically quantifiable (such as in
             the case of skin disease)

          8. ECOG performance status of 0 - 1.

          9. Prior treatment with any number of immunotherapies (e.g., IL2, ipilimumab), targeted
             therapies (e.g., vemurafenib) are permitted but no more than one 1 prior chemotherapy

         10. Acceptable liver function

         11. Acceptable renal function

         12. Acceptable hematologic status (without growth factor support for neutropenia or
             transfusion dependency):

         13. Normal 12-lead ECG (clinically insignificant abnormalities permitted)

         14. Female subjects of childbearing age must have a negative urine HCG test unless prior
             hysterectomy or menopause (defined as age above 55 and twelve months without menstrual
             activity). Female subjects should not become pregnant or breast-feed while on this
             study. Sexually active male and female subjects should use effective birth control.

        Exclusion Criteria:

          1. Anticancer treatment with radiation therapy, targeted therapies, chemotherapy,
             immunotherapy, hormones or other antitumour therapies within 28 days prior to first
             dose of TH-302.

          2. Subjects who have received any other investigational drug or agent within 28 days of
             first dose of TH-302

          3. Current use of drugs with known cardiotoxicity

          4. Significant cardiac dysfunction:

          5. Seizure disorders requiring anticonvulsant therapy

          6. Progressing brain metastases (unless previously treated and stable disease for a
             period of greater than or equal to 3 months on repeat MRI following definitive
             treatment).

          7. History of other malignancies, except: adequately treated non-melanoma skin cancer,
             curatively treated in-situ cancer of the cervix, or other solid tumours curatively
             treated with no evidence of disease for greater than 2 years

          8. Severe chronic obstructive or other pulmonary disease with hypoxemia (requires
             supplementary oxygen, symptoms due to hypoxemia or oxygen saturation less than 90% by
             pulse oximetry after a 2 minute walk) or in the opinion of the investigator any
             physiological state likely to cause hypoxia of normal tissue.

          9. Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1,
             without complete recovery

         10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy

         11. Prior therapy with an hypoxic cytotoxin

         12. Known infection with HIV or active infection with hepatitis B or hepatitis C

         13. History of allergic reaction to a structural compound or biological agent similar to
             TH-302

         14. Pregnancy or breast-feeding

         15. Concomitant disease or condition that could interfere with the conduct of the study,
             or that would, in the opinion of the investigator, pose an unacceptable risk to the
             subject in this study

         16. Unwillingness or inability to comply with the study protocol for any reason.