SJG-136 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery

A Phase I Dose Escalation Study of Daily x 3 Intravenous SJG-136 in Patients With Advanced Solid Tumors

This phase I trial studies the side effects and best dose of SJG-136 in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: SJG-136

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and recommended phase II dose of SJG-136 in patients with metastatic or unresectable solid tumors.

II. Determine the safety and dose-limiting toxic effects of this drug in these patients.

III. Determine, preliminarily, the efficacy of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetic parameters of this drug and its metabolites in these patients.

II. Correlate pharmacokinetic parameters with clinical effects of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive SJG-136 intravenously (IV) over 20 minutes once daily on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 patients receive escalating doses of SJG-136 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

After completion of study treatment, patients are followed up for 30 days.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• Prior chemotherapy or immunotherapy allowed
• Time interval must be at least 4 weeks since prior chemotherapy or immunotherapy, 6 weeks if the last regimen included BCNU or mitomycin C
• Radiation therapy to < 25% of hematopoietic bone marrow is allowed
• ECOG performance status =<2 (Karnofsky >= 60%)
• Life expectancy of greater than three months
• Recovered from prior therapy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Bilirubin normal
• AST and ALT =< 2.5 times upper limit of normal
• Creatinine =< 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
• No unstable angina pectoris

Exclusion Criteria:

• Patients receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study
• Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SJG-136, breastfeeding should be discontinued if the mother is treated with SJG-136
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SJG-136
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with SJG-136
• With the exception of alopecia (and other situations in which the organ dysfunction or symptoms are considered clinically insignificant or irrelevant to this study), patients may not have baseline organ dysfunction or symptoms that qualify as Grade 2 or greater by CTC AE v. 3.0
• No other chemotherapy, immunotherapy, radiation therapy, surgery for cancer (including resection of any metastases), specific antitumor therapy, or experimental medications will be permitted while the patients are participating in this study
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Palliative radiation therapy is not allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (SJG-136); Patients receive SJG-136 IV over 20 minutes once daily on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: SJG-136; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity	21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Bivariate response variable (tumor response) evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST)	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Igor Puzanov, Vanderbilt-Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: July 19, 2005
• First Submitted That Met QC Criteria: July 19, 2005
• First Posted (Estimate): July 21, 2005

Study Record Updates

• Last Update Posted (Estimate): February 24, 2014
• Last Update Submitted That Met QC Criteria: February 21, 2014
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NCI-2009-00085 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA068485 (U.S. NIH Grant/Contract); U01CA099177 (U.S. NIH Grant/Contract); CDR0000653877; PHI 0453 (Other Identifier: Vanderbilt-Ingram Cancer Center); 6816 (Other Identifier: CTEP)