Methoxyamine and Temozolomide in Treating Patients With Advanced Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00892385
First received: May 1, 2009
Last updated: October 23, 2014
Last verified: October 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as methoxyamine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving methoxyamine together with temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of methoxyamine when given together with temozolomide in treating patients with advanced solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: methoxyamine
Drug: temozolomide
Genetic: DNA analysis
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Methoxyamine and Temozolomide in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of methoxyamine [ Time Frame: Courses repeat every 28 days in the absence of unacceptable toxicity. ] [ Designated as safety issue: Yes ]
  • Dose limiting toxicities of the combination of methoxyamine and temozolomide [ Time Frame: Courses repeat every 28 days in the absence of unacceptable toxicity. ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics methoxyamine and temozolomide, when given alone or in combination [ Time Frame: Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects. ] [ Designated as safety issue: No ]
  • Pharmacokinetic profile of methoxyamine after single one-hour IV administration [ Time Frame: PK data during and following single one-hour MX infusion may be obtained in all subsequent cycles (cycles 3 and beyond) as necessary. ] [ Designated as safety issue: No ]
  • Biological activity, evidenced by a 40% drop in detectable apurinic/apyrimidinic sites in blood mononuclear cells [ Time Frame: Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects. ] [ Designated as safety issue: No ]
  • DNA strand breaks in blood mononuclear cells as assessed by comet assay [ Time Frame: Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects. ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: August 2007
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: methoxyamine and temozolomide Drug: methoxyamine
Methoxyamine IV over 1 hour every 28 days. Methoxyamine IV administration will follow, within 5 minutes, initial administration of TMZ on day 1.
Drug: temozolomide
Patients receive oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Genetic: DNA analysis
Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects. Samples are analyzed for DNA strand break determination by comet assay.
Other: laboratory biomarker analysis
Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects. Samples are analyzed for apurinic/apyrimidinic sites.
Other: pharmacological study
Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects. Samples are analyzed for methoxyamine and temozolomide pharmacokinetics.

Detailed Description:

OBJECTIVES:

  • To determine the maximum tolerated dose of methoxyamine given in conjunction with temozolomide in patients with and without CNS disease.
  • To determine the dose limiting toxicities of the combination of methoxyamine and temozolomide in patients with and without CNS disease.
  • To determine the pharmacokinetics of these two agents when given alone or in combination, as well as the pharmacokinetic profile of methoxyamine after single one-hour IV administration.
  • To determine relative DNA damage, as single or double strand breaks by comet assay in blood mononuclear cells which will serve as a surrogate for tumor response to the drug combination.

OUTLINE: This is a dose escalation study of methoxyamine.

Patients receive oral temozolomide for 5 days every 28 days and methoxyamine IV over 1 hour every 28 days. Methoxyamine IV administration will follow, within 5 minutes, initial administration of TMZ on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for correlative studies. Samples are analyzed for methoxyamine and temozolomide pharmacokinetics, apurinic/apyrimidinic sites, and DNA strand break determination by comet assay.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a histologically confirmed solid tumor that is considered incurable and is not amenable to conventional surgical, radiation therapy or chemotherapy treatment programs.
  • Prior chemotherapy and/or radiation are allowed. At least 3 weeks must have elapsed since prior large-field radiation therapy; patients must have been off previous anti-cancer therapy for at least 3 weeks (6 weeks for mitomycin-C and nitrosoureas); and recovered from all treatment related toxicity to < grade 1 according to NCI CTCAE version 3.0 (with the exception of alopecia and radiation-induced taste changes). Prior temozolomide treatment is not restricted.
  • ECOG performance status (PS) 0-2 (Karnofsky PS 50-100%)
  • Life expectancy ≥ 12 weeks
  • Patients must have normal organ and marrow function as defined below:

    • Absolute neutrophil count ≥ 1,500/μL
    • Platelet count ≥ 100,000/μL
    • Hemoglobin ≥ 10.0 g/dL
    • Total bilirubin ≤ 1.5 mg/dL
    • AST ≤ 2.5 times upper limit of normal
    • Creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 60 mL/min
  • Patients with known primary or metastatic CNS disease, are eligible for participation in cohort B, but not in cohort A.
  • 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients may not be receiving any other investigational agents or have received other investigational agents for at least 3 weeks.
  • 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 and lactating women are excluded from this study because the methoxyamine and temozolomide combination is likely to be teratogenic.
  • NYHA classification III or IV heart disease
  • Patients with known primary or metastatic CNS disease (cohort B) are not eligible if they have a mini mental status exam score < 15 or evidence of leptomeningeal disease.
  • Patients with pre-existing neurologic toxicity > grade1 (as per CTCAE, version 3.0) are not eligible for participation in cohort A.
  • Patients screened for participation in cohort B with pre-existing neurologic toxicity > grade 2 (as per CTCAE, version 3.0) are not eligible, unless pre-existing neurologic toxicity is documented in detail and patient's participation in the trial has been approved by the neuro-oncology team at participating institutions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892385

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jennifer Eads, MD    216-844-6003    jennifer.eads@uhhospitals.org   
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Jennifer Eads, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00892385     History of Changes
Other Study ID Numbers: CASE1Y05, P30CA043703, CASE1Y05, WIRB-20070151, NCI-2009-01286
Study First Received: May 1, 2009
Last Updated: October 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014