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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00086970

Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors

A Phase 1 study testing ifosfamide and O6-benzylguanine in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ifosfamide and O6-benzylguanine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
Jun 2004to Nov 2005
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed solid tumor
  • Unresectable, metastatic disease
  • No primary tumors
  • Eligible for high-dose ifosfamide-based therapy
  • No known brain metastases
  • Performance status - ECOG 0-1
Show all 38Show fewer
  • Performance status - Karnofsky 70-100%
  • More than 12 weeks
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal
  • Creatinine normal
  • Creatinine clearance ≥ 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 weeks after study participation
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
  • No concurrent uncontrolled illness
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study compliance
  • More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
  • No prior hematopoietic stem cell transplantation
  • No concurrent pegfilgrastim
  • No concurrent immunotherapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy
  • More than 4 weeks since prior radiotherapy and recovered
  • No concurrent therapeutic radiotherapy
  • More than 4 weeks since prior anticancer therapy
  • No more than 2 prior cytotoxic regimens
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies
  • No other concurrent investigational agents

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637-1470

Other trials in United States

About this study

Official title: A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors

This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors. Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining ifosfamide with O(6)-benzylguanine may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.

II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.

III. Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.

IV. Determine the safety and toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

  1. Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.

II. Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.

OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.

Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.

Course 2: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive high-dose ifosfamide as in course 1.

Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.

Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover. In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Being tested
ifosfamide, O6-benzylguanine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ifosfamideDrug

    Also called Cyfos, Holoxan, IFF, IFX

    Given IV

  • O6-benzylguanineDrug

    Also called BG

    Given IV

Study groups in NCT00086970
Study groupRoleWhat they receive
Arm I (ifosfamide)ExperimentalPatients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Receives: Drug: ifosfamide
Arm II (O6-benzylguanine, ifosfamide)ExperimentalPatients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Receives: Drug: ifosfamide; Drug: O6-benzylguanine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia

    Measured: Baseline up to 1 year

  2. Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity

    DLT is defined as any >= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.

    Measured: 21 days

Secondary outcomes (2)

  1. Pharmacodynamics including apoptosis and DNA damage

    Measured: Up to 1 year

  2. Pharmacokinetics of O6-benzylguanine

    Summarized using descriptive statistics (mean, median, standard deviation, and interquartile range). Estimated via nonlinear regression.

    Measured: Up to day 3 of course 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jul 2004 (estimated)
  2. Study startJun 2004
  3. Primary completionNov 2005

Why it stopped: Administratively complete.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00086970
Sponsor's protocol ID
NCI-2012-02601
Other IDs
12999B, U01CA069852, CDR0000371909
Status last verified
Jan 2013
First submitted
8 Jul 2004
Last updated
24 Jan 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ifosfamide and O6-benzylguanine in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Administratively complete.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia (time frame: Baseline up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00086970.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2013.

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