A Study of Intravenous INO-1001 Plus Oral Temozolomide to Evaluate Tolerability, Safety, and Pharmacokinetics in Patients With Melanoma

Study Overview
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Brief Summary
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This is a prospective, open-label, non-randomized, multicenter study in adults, aged eighteen (18) or older, with newly-diagnosed or recurrent unresectable Stage III or Stage IV melanoma. A maximum of 18 subjects will be enrolled in Stage 1 of this study. (Stage 1 completed enrollment in June 2006.) A maximum of 39 subjects will be enrolled in Stage 2 of this study.

Official Title
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A Phase Ib, Open-Label, Multicenter Trial of Intravenous INO-1001 Plus Oral Temozolomide to Evaluate the Tolerability, Safety, and Pharmacokinetics in Subjects With Newly-Diagnosed or Recurrent Unresectable Stage III or Stage IV Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: INO-1001
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven malignant melanoma with metastasis that is unresectable Stage III or Stage IV. Subjects with recurrent melanoma that is unresectable are also eligible Measurable indicator metastases Age 18 years or older ECOG status 0-2 An interval at the time of enrollment of at least: a) 2 weeks since surgical resection (if conducted); b) 4 weeks since prior radiotherapy or chemotherapy, and c) 6 weeks since chemotherapy with a nitrosourea Hematocrit > 29%, ANC > 1500 cells/ul, platelets > 100,000 cells/ul Serum creatinine within the laboratory's upper limit of normal Serum AST and ALT ≤ 1.5 x the laboratory's upper limit of normal Subject signed informed consent prior to subject entry Exclusion Criteria: Female patients who are pregnant or breast-feeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to administration of each cycle of the study drug regimen. Subjects of childbearing potential who are not willing or able to use an effective method of contraception, consisting of at least one-barrier method (e.g., condom and diaphragm), for the duration of the study and for at least 3 months after completing the treatment. Subjects previously treated with DTIC or TMZ Symptomatic central nervous metastases Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study. Confirmed diagnosis of hepatitis or HIV infection Any medical, psychiatric, or social problem that might interfere with the performance, completion, and/or interpretation of the trial Patients who have had any surgery within two weeks prior to enrollment in this study, or who have not recovered from the side effects of this or any other therapy Patients unwilling to comply with the protocol or who in the judgment of the Principal Investigator are unable to abide by the rules of the protocol Subjects who have received a potent CYP3A4 inhibitor or inducer orally or parenterally within approximately 14 days prior to enrollment Subjects who have received amiodarone within 30 days of study drug administration History of hypersensitivity reaction to more than three (3) drugs or to mannitol Patients who have received any investigational study agent within 30 days of Day 1 of Cycle 1

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: INO-1001<br>* Intravenous repeating dose<br>Drug: temozolomide<br>* Oral repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) or recommended Phase II dose of INO-1001 to be used in combination with TMZ |  | Length of study | 
| Pharmacokinetic (PK) profile of intravenous INO-1001 |  | Length of study | 
| Safety and tolerability of combined therapy with oral temozolomide (TMZ) and intravenous INO-1001 |  | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of repeat dosing |  | Length of study | 
| Pharmacodynamic (PD) activity of intravenous INO-1001 |  | Length of study | 
| Response |  | Length of study | 
| Progression-free survival |  | Length of study | 
| Overall survival |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INO4136g, inotek, Parp, Temodar