Trial of an Intratumoral Injections of INXN-3001 in Subjects With Stage III or IV Melanoma

• Status: Completed
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the safety of an investigational combination drug/immunotherapy for the treatment of Stage III/IV melanoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ziopharm

Criteria

Inclusion Criteria:

1. Males or females of all races ≥ 18 years of age and ≤ 75 years of age;

2. Unresectable Stage III C (in transit) or Stage IV melanoma (M1a, M1b, M1c with LDH ≤ 2x ULN), arising from primary cutaneous, mucosal, or subungual melanoma of any tumor thickness or from an unknown primary site;

3. A minimum of 2-3 accessible nonvisceral lesions (longest diameter ≤3 cm) or palpable tumor-involved lymph nodes (longest diameter ≤5 cm) for intratumoral injections (INXN-3001) and biopsies;

4. ECOG performance status of 0 or 1;

5. Patients without visible brain metastases as assessed by contrast-enhanced MRI scan within 6 weeks prior to receiving study treatment;

6. Adequate baseline hematological and organ function, assessed by laboratory values within 42 days (6 weeks) prior to study entry and prior to repeat treatment cycles with INXN-1001 as follows: hemoglobin ≥ 10 g/L, granulocytes > 2500/mm3, lymphocytes > 1000/ mm3, platelets > 100,000/ mm3, serum creatinine < 1.5 x ULN, AST, ALT, alkaline phosphatase < 2.5 x ULN, LDH ≤ 2 x ULN, serum bilirubin < 1.5 x ULN, absolute neutrophils > 500/ mm3;

7. An expected survival of at least approximately 6 months in the opinion of the investigator (as assessed mainly by performance status);

8. Females must be post-menopausal or surgically sterile or practice effective contraception; Men who are not surgically sterile and whose partners are not post-menopausal or surgically sterile must practice effective contraception;

9. Normal coagulation parameters as measured by PT/PTT;

10. Signed, IRB-approved voluntary written informed consent.

Exclusion Criteria:

1. Active, acute viral, bacterial, or fungal infections requiring specific therapy;

2. HIV-infection due to concerns about ability to mount an effective immune response;

3. Active autoimmune disease requiring steroids (>10 mg prednisolone or comparable) or other immunosuppressive therapy;

4. Patients with detectable brain metastases at the time of screening (or within 6 weeks prior to receiving study treatment), as assessed by contrast-enhanced MRI scans;

5. Patients with one or more lesion(s) > 3cm (LD) or palpable, tumor-involved lymph node(s) >5 cm (LD);

6. Patients with a hemoglobin of < 10 g/L;

7. Presence of Stage IV visceral metastases or other distant metastases if LDH >2 x ULN;

8. Patients who have previously been treated with INXN-3001 and INXN-1001;

9. Recipients of organ allografts;

10. Other concurrent, clinically active malignant disease, with the exception of other cancers of the skin;

11. Less than 30 days (before the first dose of study medication) have elapsed since the completion of prior chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any first line therapy;

12. Clinically significant cerebrovascular disease;

13. History of or concurrent severe cardiac insufficiency (New York Heart Association Class III or IV) or coronary artery disease;

14. QTc interval of >470 ms on screening;

15. Inability to measure the QT interval due to conduction abnormalities such as Bundle Branch Block (left or right) or persistent cardiac arrhythmia e.g. atrial fibrillation, or cardiac pacemaker;

16. Long QT syndrome or family history of sudden cardiac death in young family members;

17. Concomitant use of medication known to affect ventricular repolarization;

18. Cardiac comorbidity such as a left ventricular ejection fraction <45%, myocardial infarction, persistent angina, or cardiac surgery within 3 months prior to enrollment;

19. Uncontrollable hypertension (>150 mm Hg systolic or >100 mm Hg diastolic);

20. Acute medical conditions such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk;

21. History of or current bleeding or uncorrected clotting disorders;

22. Concurrent immunosuppressive therapy such as corticosteroids (>10mg prednisolone or comparable) and cyclosporin A;

23. Concurrent investigational treatments, or treatment with any investigational treatment within the past 30 days (prior to the first dose of study medication);

24. Concurrent medications that are metabolized by the CYP 3A4 pathway;

25. Females who are lactating or pregnant;

26. A Body Mass Index (BMI) greater than or equal to 40 kg/m2; aa. Patients who have a history of hypersensitivity that may relate to any component of the product, e.g. to benzoic acid that might be related to INXN-1001, which contains two benzene rings; bb. Any medical or psychiatric condition which, in the opinion of the investigator, would unacceptably reduce the safety or delivery of the proposed treatment, or would preclude obtaining voluntary informed consent.