A Phase I/II Study of GMX1777 in Combination With Temozolomide for the Treatment of Metastatic Melanoma

Study Overview
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Brief Summary
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Obatoclax Mesylate (GMX1777) is a water-soluble, intravenously-administered pro-drug of GMX1778. GMX1777 is rapidly converted to GMX1778 in vivo. GMX1778 has potent anti-tumor activity against a variety of cell lines and models from different tumor origins.

Detailed Description
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GMX1777 will be administered as 3-Hour Infusions in Combination with Temozolomide taken orally for the treatment of Metastatic Melanoma. GMX1777 infusion will be given on either day 1, days 1 and 3, or days 1,3, and 5 every 4 weeks. Temozolomide will be administered on 5 consecutive days every 4 weeks. No investigational or commercial agents or therapies other than those described may be administered with the intent to treat the patient's malignancy.

Official Title
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A Multi-Center, Open-Label, Phase I/II Study of GEM1777 in Combination With Temozolomide Administered Every 4 Weeks to Patients With Metastatic Melanoma

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: Obatoclax Mesylate
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic melanoma Up to 1 prior chemotherapy regimen allowed; prior immunotherapy allowed Normal organ and marrow function Willing to submit to blood sampling for planned PK/PD analyses Ability of understand and willingness to sign a written informed consent Exclusion Criteria: No other investigational or commercial agents or therapies Prior exposure to GMX1777, GMX1778 or CHS828 Patients with uncontrolled, intercurrent illness Pregnant or breastfeeding women

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>40 mg/m2 GMX1777 with Temozolomide | Drug: Obatoclax Mesylate<br>* Obatoclax Mesylate (GMX1777) at various doses in combination with temozolomide<br>* Other names: GMX1777;Drug: Temozolomide<br> <br> |
| Experimental: 2<br>50 mg/m2 GMX1777 with Temozolomide | Drug: Obatoclax Mesylate<br>* Obatoclax Mesylate (GMX1777) at various doses in combination with temozolomide<br>* Other names: GMX1777;Drug: Temozolomide<br> <br> |
| Experimental: 3<br>62 mg/m2 GMX1777 with Temozolomide | Drug: Obatoclax Mesylate<br>* Obatoclax Mesylate (GMX1777) at various doses in combination with temozolomide<br>* Other names: GMX1777;Drug: Temozolomide<br> <br> |
| Experimental: 4<br>80 mg/m2 GMX1777 with Temozolomide | Drug: Obatoclax Mesylate<br>* Obatoclax Mesylate (GMX1777) at various doses in combination with temozolomide<br>* Other names: GMX1777;Drug: Temozolomide<br> <br> |
| Experimental: 5<br>100 mg/m2 GMX1777 with Temozolomide | Drug: Obatoclax Mesylate<br>* Obatoclax Mesylate (GMX1777) at various doses in combination with temozolomide<br>* Other names: GMX1777;Drug: Temozolomide<br> <br> |
| Experimental: 6<br>125 mg/m2 GMX1777 with Temozolomide | Drug: Obatoclax Mesylate<br>* Obatoclax Mesylate (GMX1777) at various doses in combination with temozolomide<br>* Other names: GMX1777;Drug: Temozolomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the recommended Phase II dose of GMX1777 in combination with temozolomide |  | 2 years | 
| Learn more about the side effects of taking GMX1777 in combination with temozolomide |  | Within the first 4 weeks | 
| Determine the disease response to treatment with GMX1777 in combination with temozolomide |  | Within the first 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Learn more about how the body processes GMX1777 |  | Within the fisrt 30 days |