Study to Evaluate Sodium Stibogluconate With Interferon Alpha-2b

Solid Tumors Clinical Trial

Official title:

A Phase IIa, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Sodium Stibogluconate in Combination With Interferon Alpha-2b for Patients With Advanced Malignancies

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01479309
• Other study ID #: 2006-0354 IIa
• Secondary ID: 2006-0354
• Status: Withdrawn
• Phase: Phase 2
• First received: November 21, 2011
• Last updated: November 23, 2011
• Start date: September 2006
• Est. completion date: February 2010

Study information

• Verified date: November 2011
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical research study is to expand the research following finding the highest tolerable dose of sodium stibogluconate combined with interferon alfa-2b in the treatment of patients with advanced cancer that has not responded to standard treatment or where there is no standard treatment for this type of cancer.

Description:

Primary objectives:

To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of SSG in combination with IFN alpha2b in patients with advanced malignancies.

Secondary objective:

• To correlate the AUC of SSG with clinical toxicity and efficacy;

• To quantify the effect of SSG on IFN alpha2b induced gene modulation and signal transduction pathways;

• To characterize the effects of SSG on PTPases SHP-1 and SHP-2.

To assess the safety, efficacy, and PK of SSG in combination with IFN alpha2b.

Treatment:

During Cycle 1, you will be given sodium stibogluconate once a day by vein during Days 1-5. On Days 8-12, you will be given sodium stibogluconate once a day by vein, and you will be given interferon alfa-2b for 3 days by injection just under the skin on Days 8, 10, and 12. For every cycle after Cycle 1, you will be given sodium stibogluconate once a day by vein during Days 1-5 and 8-12, and you will be given interferon alfa-2b for 3 days by injection just under the skin on Days 1, 3,5, 8, 10, and 12. Treatment cycles will last about 3 weeks (2 weeks on treatment, followed by 1 week off treatment). After Cycle 1, you will be scheduled to return to the clinic in 10 days to receive treatment for Cycle 2, which will follow in the same manner as Cycle 1.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients who sign a written informed consent document and are able to comply with the study protocol for the duration of the study.

2. Patients who have a histologically or cytologically confirmed diagnosis malignancy (patients with measurable or non-measurable disease) who have progressed following effective therapy or for which no effective therapy exists.

3. Patients who are greater than or equal to 18 years of age.

4. Patients who have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

5. Patients who have an estimated life expectancy of 3 months.

6. Patients who have a normal cardiac ejection fraction, >50% estimated by 2 D Echocardiogram or MUGA.

7. Patients who have adequate organ function as indicated by the following laboratory values obtained within 10 days prior to the first dose of SSG: Granulocytes>/=1,500 microliter, Platelets>/= 100,000 microliter, Hemoglobin >/=9.0 g/dL,Creatinine (Cr) </= 1.5 mg/dL, Bilirubin Normal limits, or <2.0 x ULN with liver metastases, Aspartate aminotransferase (AST) <2.5 * ULN or <5.0 * ULN with liver metastases, Alanine aminotransferase (ALT)<2.5 * ULN or <5.0 * ULN with liver metastases.

Exclusion Criteria:

1. Patients on concurrent immunotherapy, including IFN therapy (prior therapy is allowed if >/= 4 months since immunotherapy).

2. Patients who have received investigational drugs including immunotherapy, gene therapy, hormone therapy, biologic therapy, radiation therapy, chemotherapy, or had major surgery within 3 weeks of study enrollment

3. Patients who have not recovered from acute toxicity of previous therapy prior to enrollment.

4. Patients with medically uncontrolled cardiovascular illness, unstable angina, congestive heart failure, history of myocardial infarction, electrocardiogram (ECG) abnormalities suggestive of cardiac conduction delay (QTc >0.47 seconds), history of atrial fibrillation or flutter, or other serious clinically significant cardiac arrhythmia

5. Patients who have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant.

6. Pregnant or lactating women, and fertile women or men unless surgically sterile or using effective contraception; All female patients of childbearing potential or < 1 year postmenopausal must have a negative beta human chorionic gonadotropin (ßhCG) pregnancy test at baseline and be practicing a medically acceptable method of birth control (oral contraceptives for at least 3 months, implantation of an intrauterine device at least 2 months, or barrier methods [e.g. vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly]). These must be continued for 3 months after study initiation

7. Patients who use daily glucocorticoids except for physiological replacement.

8. Patients who are known to be positive for Hepatitis B surface antigen, Hepatitis C or human immunodeficiency virus (HIV).

9. Patients with prior history of solid organ allografts or allogeneic bone marrow transplant.

10. Patients who have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.

11. Patients who have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

12. Patient who have symptomatic or untreated central nervous system metastases.

13. Patients taking the following medications will not be eligible: Amiodarone (Cordarone); Disopyramide (Norpace); Dofetilide (Tikosyn); Procainamide (Procanbid, Pronestyl); Quinidine (Quinaglute); Sotalol (Betapace); Erythromycin; Azithromycin (Z-pack), cont'd

14. Clarithromycin (Biaxin); Pentamidine (Pentacarinat); Trimethoprim-sulfamethoxazole (Bactrim); Bepridil (Vascor); Phenothiazines-prochlorperazine (Compazine), promethazine (Phenergan), chlorpromazine (Thorazine) or any antipsychotic medication; Butyrophenones-Haloperidol (Haldol), cont'd

15. Risperidone (Risperdal); Tricyclic or tetracyclic antidepressants—imipramine (Tofranil), amitriptyline (Elavil), desipramine (Norpramin), nortriptyline (Pamelor); Monoamine oxidase inhibitors; High dose methadone; Arsenic trioxide; Dolasetron (Anzemet); Any herbal preparations; or • Chronic need for colony stimulating factors (i.e., GM-CSF), erythropoietin use is permitted.

16. Patients with a history of hypersensitivity to IFN a-2b or SSG or any of their components.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Cancer
• Solid Tumors

Intervention

Drug:
• Sodium Stibogluconate
400 mg/m^2 IV daily on days 1-5.
• Interferon Alpha-2b
3x10^6 units subcutaneously three times weekly

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	VioQuest Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of SSG in combination with IFN alpha2b	MTD defined as the highest dose at which no dose limiting toxicity (DLT) occurs. Continuous assessment with each 3 week cycle.	3 weeks	Yes

External Links

•   UT MD Anderson Cancer Center website