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

Sigma-Tau Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Malignant Melanoma

Treatments: Biological: Dacarbazine + Thymosin-alpha-1 3.2 mg; Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg; Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg; Drug: Dacarbazine + Interferon alpha; Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00911443

ST1472DM01012

Details and patient eligibility

About

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%).

Enrollment: 488 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

488 participants in 5 patient groups

Dacarbazine + Interferon alpha + thymosin-alpha-1 1.6 mg

Experimental group

Description:

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.

Treatment:

Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg

Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg

Experimental group

Description:

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.

Treatment:

Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg

Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg

Experimental group

Description:

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.

Treatment:

Biological: Dacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg

Dacarbazine + Thymosin-alpha-1 3.2 mg

Experimental group

Description:

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.

Treatment:

Biological: Dacarbazine + Thymosin-alpha-1 3.2 mg

Dacarbazine + Interferon alpha

Active Comparator group

Description:

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.

Treatment:

Drug: Dacarbazine + Interferon alpha