A Phase 2 Biomarker - Enriched Study of TH-302 in Subjects With Advanced Melanoma

• Status: Terminated
• Trial end date: 2015-09-01
• Target enrollment: 0
• Participant gender: All

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.

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

Details

• Lead Sponsor: Threshold Pharmaceuticals

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.