Sodium Stibogluconate and IFNa-2b Followed By CDDP, VLB and DTIC Treating Pts.With Advanced Melanoma or Other Cancers

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00498979

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Sodium stibogluconate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers. Drugs used in chemotherapy, such as cisplatin, vinblastine, and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sodium stibogluconate and interferon alfa-2b together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of sodium stibogluconate when given together with interferon alfa-2b, cisplatin, vinblastine, and dacarbazine in treating patients with advanced melanoma or other cancer.

Condition or Disease	Intervention/Treatment	Phase
Stage IV Melanoma	Biological: recombinant interferon alfa-2b Drug: cisplatin Drug: sodium stibogluconate Drug: dacarbazine Drug: vinblastine	Phase 1

Detailed Description

OBJECTIVES:

Primary

To determine the safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy.
To confirm the activity of sodium stibogluconate in augmenting cytokine effects.

Secondary

To quantify the effects of sodium stibogluconate on interferon alfa-2b induced gene modulation and signal transduction pathways by measuring the serum soluble gene products.
To define the effectiveness of sodium stibogluconate in inhibiting the protein tyrosine phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes of patients receiving sodium stibogluconate in combination with interferon alfa-2b.
To define the pharmacokinetics of sodium stibogluconate in serum at escalating doses.
To assess clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy.

OUTLINE:

Course 1: Patients receive sodium stibogluconate IV over 15 minutes on day 1 and days 15-18; interferon alfa-2b subcutaneously (SC) on days 8-12 and 15-18; cisplatin IV over 30-60 minutes and vinblastine IV on days 19 and 20; and dacarbazine. After a 2-week rest period, patients proceed to course 2.
Course 2 and all subsequent courses: Patients receive sodium stibogluconate IV over 15 minutes and interferon alfa-2b SC on days 1-4; cisplatin IV over 30-60 minutes and vinblastine IV on days 5 and 6; dacarbazine. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.* NOTE: *Patients with stage IV disease who have no evidence of disease [NED} receive only 4 courses of therapy.

Cohorts of 6 patients receive escalating doses of sodium stibogluconate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which dose-limiting toxicity occurs (i.e., no more than 1 patient at a given dose experiences DLT).

Patients undergo blood sample collection periodically for immunological and pharmacokinetic studies. Samples are analyzed for serum soluble gene products and protein tyrosine phosphatase inhibition.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b Followed by Cisplatin, Vinblastine and Dacarbazine for Patients With Melanoma or Malignancies Potentially Responsive to SSG and/or Interferons

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: recombinant interferon alfa-2b recombinant interferon alfa-2b	Biological: recombinant interferon alfa-2b recombinant interferon alfa-2b Other Names: IFN 2b Drug: cisplatin recombinant interferon alfa-2b Other Names: CDDP Drug: sodium stibogluconate sodium stibogluconate Drug: dacarbazine dacarbazine Other Names: DTIC Drug: vinblastine vinblastine Other Names: VBL

Arm

Intervention/Treatment

Experimental: recombinant interferon alfa-2b

recombinant interferon alfa-2b

Biological: recombinant interferon alfa-2b

recombinant interferon alfa-2b

Other Names:

IFN 2b

Drug: cisplatin

recombinant interferon alfa-2b

Other Names:

CDDP

Drug: sodium stibogluconate

sodium stibogluconate

Drug: dacarbazine

dacarbazine

Other Names:

DTIC

Drug: vinblastine

vinblastine

Other Names:

VBL

Outcome Measures

Primary Outcome Measures

Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy [2 years]

Secondary Outcome Measures

Effects of sodium stibogluconate on interferon alfa-2b induced gene modulation and signal transduction pathways by measuring the serum soluble gene product [2 years]
Effectiveness of sodium stibogluconate in inhibiting the protein tyrosine phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes [2 years]
Pharmacokinetics of sodium stibogluconate in serum at escalating doses [2 years]
Clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed melanoma or other malignancies
Must be refractory or resistant to established treatments OR have metastatic disease for which no effective therapy has been established
Gliomas or controlled CNS metastasis allowed
A CT scan or MRI must confirm stable brain metastases within 28 days of study entry
Patients with primary CNS malignancies refractory to other therapies are eligible
Malignancy potentially responsive to sodium stibogluconate and/or interferon alfa-2b and combination chemotherapy
Patients must have measurable or evaluable disease
Evaluable disease can include clinically or radiographically nonmeasurable tumor, specific tumor markers, or stage IV patients with no evidence of disease (NED)

PATIENT CHARACTERISTICS:

Inclusion criteria:
ECOG performance status 0-2
Granulocytes > 1,500/μl
Platelets > 100,000/μl
Creatinine < 1.5 x upper limit of normal (ULN)
Bilirubin < 1.5 x ULN
AST and ALT < 1.5 x ULN (unless due to hepatic metastases)
Potassium ≤ 5.0 mmol/L
Magnesium ≤ 2.4 mg/dL
Creatinine clearance ≥ 60 cc/min
Ejection fraction ≥ 50%
Exclusion criteria:
Pregnant or lactating women and fertile women or men unless surgically sterile or using effective contraception
All female patients of childbearing potential or less than 1 year postmenopausal must have a negative β-HCG pregnancy test at baseline and practice a medically acceptable method of birth control (i.e., oral contraceptives for at least 3 months, implantation of an intrauterine device for at least 2 months, or barrier methods [e.g., vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly]) during and for 3 months after study initiation
History of atrial fibrillation, flutter, or other serious arrhythmia (excluding asymptomatic atrial or ventricular premature complexes) in the past 24 months
History of congestive heart failure currently requiring treatment; angina pectoris; or other severe cardiovascular disease (i.e., New York Heart Association class III or IV heart disease)
Baseline ECG abnormalities suggestive of cardiac conduction delay (i.e., first degree or greater atrio-ventricular block and/or complete or incomplete [QRS > 120 ms] bundle branch block)
Baseline ECG abnormalities suggestive of repolarization abnormalities (i.e., QTc ≥ 0.48 sec)
Culture positive acute infections requiring antibiotics within the past 14 days
Patients on long term suppressive antibiotic therapies are eligible
Known to be positive for HBsAg
Patients judged to not be psychologically prepared to understand informed consent or comply with an investigational study

PRIOR CONCURRENT THERAPY:

Inclusion criteria:
Prior interferon therapy is allowed if administered ≥ 4 months ago
At least 3 weeks since prior major surgery, radiation therapy, or chemotherapy
Exclusion criteria:
No prior treatment with interferon, sodium stibogluconate, cisplatin, vinblastine, or dacarbazine, except if given in an adjuvant setting
Patients with a prior history of solid organ allografts or allogeneic bone marrow transplant
Patients taking the following medications will not be eligible:
Amiodarone (Cordarone)
Disopyramide (Norpace)
Dofetilide (Tikosyn)
Procainamide (Procanbid or Pronestyl)
Quinidine (Quinaglute)
Sotalol (Betapace)
Erythromycin
Azithromycin (Z-pack)
Clarithromycin (Biaxin)
Pentamidine (Pentacarinat)
Trimethoprim-sulfamethoxazole (Bactrim)
Bepridil (Vascor)
Phenothiazines (e.g., prochlorperazine [Compazine], promethazine [Phenergan], or chlorpromazine [Thorazine])
Butyrophenones (e.g., Haloperidol [Haldol])
Risperidone (Risperdal)
Any other antipsychotic medication
Tricyclic or tetracyclic antidepressants (e.g., imipramine [Tofranil], amitriptyline [Elavil], desipramine [Norpramin], or nortriptyline [Pamelor])
Monoamine oxidase inhibitors
High-dose methadone
Arsenic trioxide
Dolasetron (Anzemet)
Any herbal preparations
Use of daily glucocorticoids except for physiological replacement