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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Advanced Cancer, Solid Tumors

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Trial Information

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


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.


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)
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 (βhCG)
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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose (MTD) of SSG in combination with IFN alpha2b

Outcome Description:

MTD defined as the highest dose at which no dose limiting toxicity (DLT) occurs. Continuous assessment with each 3 week cycle.

Outcome Time Frame:

3 weeks

Safety Issue:

Yes

Principal Investigator

Aung Naing, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2006-0354 IIa

NCT ID:

NCT01479309

Start Date:

September 2006

Completion Date:

February 2010

Related Keywords:

  • Advanced Cancer
  • Solid Tumors
  • Advanced Malignancies
  • Solid Tumors
  • Melanoma
  • Renal Cell Carcinoma
  • Phase I Studies
  • Sodium Stibogluconate
  • Interferon Alpha-2b
  • Intron A
  • SSG
  • Neoplasms

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