Thymosin Alpha 1, Interferon Alpha, or Both, in Combination With Dacarbazine in Patients With Malignant Melanoma

Study Overview
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Brief Summary
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The purpose of the study is to test safety and efficacy of different doses of thymosin alpha 1 (1.6 mg, 3.2 mg, and 6.4 mg) in combination with dacarbazine and with or without Interferon alpha in treating patients affected by stage IV melanoma. Primary end-point is Tumor Response evaluated according to Response Evaluation Criteria In Solid Tumors (RECIST). Secondary end-points are Overall Survival and Progression Free Survival. Ninety-five patients are allocated to each arm to test the hypothesis that P0 <= 0.05 vs the alternative hypothesis that P1 >= 0.15 (alpha = 5%, within-group statistical analysis beta = 95%).

Official Title
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A Phase II, Multicentre, Open, Randomised, Dose Ranging Study to Investigate the Efficacy of Combination Therapy Containing Dacarbazine (DTIC) Plus Low Dose Interferon Alpha (aIFN) Plus Thymosin a1 Versus Both DTIC Plus Thymosin a1 and DTIC Plus aIFN in Patients With Advanced -Stage Metastatic Malignant Melanoma

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg
* Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg
* Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg
* Biological: Dacarbazine + Thymosin-alpha-1 3.2 mg
* Drug: Dacarbazine + Interferon alpha


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have read and signed the informed consent form 18 years <=Age<= 75 years Adequate contraception practice (fertile female patient) Confirmed diagnosis of metastatic melanoma (stage IV) with unresectable metastases and >= 1 measurable lesion Adequate renal function as demonstrated by serum creatinine level < 1.5 mg/deciliter (dl) Absolute Neutrophil Count (ANC) >= 1.5 x 10000000000/L ; platelets >= 100 x 10000000000/Liter (L) Good performance status: PS <= 1 (ZUBROD-ECOG-WHO scale) At least 12 week life expectancy Exclusion Criteria: Clinical diagnosis of autoimmune disease Transplant recipient Pregnancy documented by a urine pregnancy test or lactation Previous treatment with thymosin alpha 1 Previous treatment with chemotherapy Presence of Central Nervous System (CNS) metastases Concomitant or prior history of malignancy other than melanoma Participation in another investigational trial within 30 days of study entry Active infectious process that is not of self-limiting nature

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dacarbazine + Interferon alpha + thymosin-alpha-1 1.6 mg<br>Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 1.6 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops. | Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg<br>* Dacarbazine 800 mg/m2 IV on day 1;Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 1.6 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.<br>* Other names: Roferon;|
| Experimental: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg<br>Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops. | Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg<br>* Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.<br>* Other names: Roferon;|
| Experimental: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg<br>Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18; Thymosin-alpha-1 6.4 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops. | Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg<br>* Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18 Thymosin-alpha-1 6.4 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.<br>* Other names: Roferon;|
| Experimental: Dacarbazine + Thymosin-alpha-1 3.2 mg<br>Dacarbazine 800 mg/m2 IV on day 1; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops. | Biological: Dacarbazine + Thymosin-alpha-1 3.2 mg<br>* Dacarbazine 800 mg/m2 IV on day 1; Thymosin-alpha-1 3.2 mg SC from day 8 to 11 and from day 15 to 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.<br>* Other names: Deticene;|
| Active Comparator: Dacarbazine + Interferon alpha<br>Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops. | Drug: Dacarbazine + Interferon alpha<br>* Dacarbazine 800 mg/m2 IV on day 1; Interferon alpha 3MIU SC on day 11 and 18 of each 28 day cycle up to 6 cycles or until progression or unacceptable toxicity develops.<br>* Other names: Roferon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response | Tumor response is measured according to Response Evaluation Criteria In Solid Tumors (RECIST) computing number of Complete Response plus Partial Response | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The survival time for each patient is defined as the time between randomization and death. Patients lost to follow-up or still alive at the date of last evaluation have been censored. | 2 years | 
| Progression Free Survival | Progression Free Survival is defined as the time from the randomization to progression or death | 2 years |