Malignant Melanoma
Conditions
Brief summary
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%).
Interventions
BIOLOGICALDacarbazine + Interferon alpha + Thymosin-alpha-1 1.6 mg
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.
BIOLOGICALDacarbazine + Interferon alpha + Thymosin-alpha-1 3.2 mg
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.
BIOLOGICALDacarbazine + Interferon alpha + Thymosin-alpha-1 6.4 mg
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.
BIOLOGICALDacarbazine + Thymosin-alpha-1 3.2 mg
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.
DRUGDacarbazine + Interferon alpha
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.
Sponsors
sigma-tau i.f.r. S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Tumor Response | 1 year | Tumor response is measured according to Response Evaluation Criteria In Solid Tumors (RECIST) computing number of Complete Response plus Partial Response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | 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. |
| Progression Free Survival | 2 years | Progression Free Survival is defined as the time from the randomization to progression or death |
Countries
France, Germany, Hungary, Italy, Poland, Portugal, Spain, Switzerland
Participant flow
Recruitment details
Recruitment started on August 2002 and has been completed on January 2006. All patients were recruited at medical clinic facilities (Oncology/Dermatology departments)
Pre-assignment details
Only patients who did not meet the entry selection criteria were excluded from study entry.
Participants by arm
| Arm | Count |
|---|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg Dacarbazin 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. | 97 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg Dacarbazin 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. | 97 |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg Dacarbazin 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 cycle up to 6 cycles or until progression or unacceptable toxicity develops. | 98 |
| Dacarbazin + Thymosin-alpha-1 3.2 mg Dacarbazin 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. | 99 |
| Dacarbazin + Interferon Alpha Dacarbazin 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. | 97 |
| Total | 488 |
Baseline characteristics
| Characteristic | Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | Dacarbazin + Thymosin-alpha-1 3.2 mg | Dacarbazin + Interferon Alpha | Total | Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0.0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 31 Participants | 26 Participants | 29 Participants | 142.0 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 69 Participants | 67 Participants | 73 Participants | 68 Participants | 346.0 Participants | 69 Participants |
| Age Continuous | 54 years STANDARD_DEVIATION 14 | 56 years STANDARD_DEVIATION 13 | 56 years STANDARD_DEVIATION 11 | 57 years STANDARD_DEVIATION 12 | 55 years STANDARD_DEVIATION 13 | 54 years STANDARD_DEVIATION 14 |
| Region of Enrollment France | 7 participants | 11 participants | 6 participants | 5 participants | 43.0 participants | 14 participants |
| Region of Enrollment Germany | 22 participants | 25 participants | 10 participants | 11 participants | 85.0 participants | 17 participants |
| Region of Enrollment Hungary | 4 participants | 1 participants | 2 participants | 9 participants | 19.0 participants | 3 participants |
| Region of Enrollment Italy | 34 participants | 27 participants | 31 participants | 28 participants | 153.0 participants | 33 participants |
| Region of Enrollment Poland | 28 participants | 32 participants | 36 participants | 37 participants | 159.0 participants | 26 participants |
| Region of Enrollment Portugal | 0 participants | 0 participants | 0 participants | 1 participants | 1.0 participants | 0 participants |
| Region of Enrollment Spain | 2 participants | 2 participants | 13 participants | 6 participants | 27.0 participants | 4 participants |
| Region of Enrollment Switzerland | 0 participants | 0 participants | 1 participants | 0 participants | 1.0 participants | 0 participants |
| Sex: Female, Male Female | 50 Participants | 45 Participants | 38 Participants | 55 Participants | 226.0 Participants | 38 Participants |
| Sex: Female, Male Male | 47 Participants | 53 Participants | 61 Participants | 42 Participants | 262.0 Participants | 59 Participants |
Outcome results
Primary
Overall Tumor Response
Tumor response is measured according to Response Evaluation Criteria In Solid Tumors (RECIST) computing number of Complete Response plus Partial Response
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg | Overall Tumor Response | 7 participants |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | Overall Tumor Response | 10 participants |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | Overall Tumor Response | 6 participants |
| Dacarbazin + Thymosin-alpha-1 3.2 mg | Overall Tumor Response | 12 participants |
| Dacarbazin + Interferon Alpha | Overall Tumor Response | 4 participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg | Overall Survival | 9.3 months |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | Overall Survival | 8.6 months |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | Overall Survival | 10.3 months |
| Dacarbazin + Thymosin-alpha-1 3.2 mg | Overall Survival | 9.3 months |
| Dacarbazin + Interferon Alpha | Overall Survival | 6.6 months |
Secondary
Progression Free Survival
Progression Free Survival is defined as the time from the randomization to progression or death
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 1.6 mg | Progression Free Survival | 1.9 months |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 3.2 mg | Progression Free Survival | 1.8 months |
| Dacarbazin + Interferon Alpha + Thymosin-alpha-1 6.4 mg | Progression Free Survival | 1.8 months |
| Dacarbazin + Thymosin-alpha-1 3.2 mg | Progression Free Survival | 2.0 months |
| Dacarbazin + Interferon Alpha | Progression Free Survival | 1.8 months |