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

NCT ID: NCT00498979

Last Updated: 2020-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2012-01-31

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.

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.

Conditions

Stage IV Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

recombinant interferon alfa-2b

recombinant interferon alfa-2b

Group Type: EXPERIMENTAL

recombinant interferon alfa-2b

Intervention Type: BIOLOGICAL

recombinant interferon alfa-2b

cisplatin

Intervention Type: DRUG

recombinant interferon alfa-2b

sodium stibogluconate

Intervention Type: DRUG

sodium stibogluconate

dacarbazine

Intervention Type: DRUG

dacarbazine

vinblastine

Intervention Type: DRUG

vinblastine

Interventions

recombinant interferon alfa-2b

recombinant interferon alfa-2b

Intervention Type: BIOLOGICAL

cisplatin

recombinant interferon alfa-2b

Intervention Type: DRUG

sodium stibogluconate

sodium stibogluconate

Intervention Type: DRUG

dacarbazine

dacarbazine

Intervention Type: DRUG

vinblastine

vinblastine

Intervention Type: DRUG

Other Intervention Names

IFN 2b; CDDP; DTIC; VBL

Eligibility Criteria

Inclusion Criteria

• 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:

• 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%

• Prior interferon therapy is allowed if administered ≥ 4 months ago
• At least 3 weeks since prior major surgery, radiation therapy, or chemotherapy

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:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ernest C. Borden, MD

Role: PRINCIPAL_INVESTIGATOR

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Locations

Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CASE3Y06

Identifier Type: -

Identifier Source: org_study_id