MG98 in Treating Patients With Advanced Solid Tumors

A Phase I Study of MG98 Given as a 2 Hour Twice Weekly IV Infusion in Patients With Advanced Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of MG98 in treating patients who have advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: MG 98

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of MG98 in patients with advanced solid tumors.
• Assess the safety, toxicity, and pharmacokinetics of this treatment regimen in this patient population.
• Evaluate the effectiveness of this treatment regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study.

Patients receive MG98 IV over 2 hours twice weekly for 3 weeks. Courses are repeated every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

The dose of MG98 is escalated in cohorts of 1-6 patients 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.

Patients are followed at week 4, then at least every 3 months until relapse of disease.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 10-12 months.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 1C4
      • Ottawa Regional Cancer Centre
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven advanced solid tumor unresponsive to existing therapy or for which no curative therapy exists
• Evidence of disease in addition to tumor marker elevation
• CNS metastases allowed, if adequately treated and symptoms controlled for greater than 4 months

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• PTT normal

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 3 times ULN (4 times ULN for liver metastases)

Renal:

• Creatinine no greater than 1.25 times ULN
• Proteinuria less than 2+ (no greater than 500 mg in a 24 hour urinalysis)

Other:

• No active infection
• No other serious systemic disease
• No known hypersensitivity to oligodeoxynucleotides
• Adequate venous access
• No known condition (e.g., psychological, geographical) that would prevent compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after the study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent colony stimulating factors unless evidence of neutropenic infection

Chemotherapy:

• No more than 3 prior chemotherapy regimens
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
• At least 1 year since prior high dose chemotherapy with bone marrow or stem cell support
• No concurrent chemotherapy

Endocrine therapy:

• Prior hormonal therapy allowed
• No concurrent hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• Concurrent palliative radiotherapy allowed

Surgery:

• At least 2 weeks since prior major surgery

Other:

• At least 3 weeks since prior investigational drug therapy
• No other concurrent investigational drug or anticancer therapy
• No concurrent coumadin or heparin therapy

Study Plan

How is the study designed?

Design Details

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

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Ross C. Donehower, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

General Publications

• Stewart DJ, Donehower RC, Eisenhauer EA, Wainman N, Shah AK, Bonfils C, MacLeod AR, Besterman JM, Reid GK. A phase I pharmacokinetic and pharmacodynamic study of the DNA methyltransferase 1 inhibitor MG98 administered twice weekly. Ann Oncol. 2003 May;14(5):766-74. doi: 10.1093/annonc/mdg216.

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 1999
• Primary Completion (Actual): September 27, 2001
• Study Completion (Actual): September 22, 2008

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: August 19, 2003
• First Posted (Estimate): August 20, 2003

Study Record Updates

• Last Update Posted (Actual): April 6, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Other Study ID Numbers: I125; CAN-NCIC-IND125 (Other Identifier: PDQ); METHYL-MG98-002 (Other Identifier: Methylgene Inc.); CDR0000067059 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No