Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00892385
Methoxyamine and Temozolomide in Treating Patients With Advanced Solid Tumors
A Phase 1 study testing Methoxyamine and Temozolomide in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- Methoxyamine and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2007to 8 Mar 2017
- 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
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106
About this study
Official title: A Phase I Study of Methoxyamine and Temozolomide in Patients With Advanced Solid Tumors
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.
Read the 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.
- Being tested
- Methoxyamine, Temozolomide
- Keywords
- unspecified adult solid tumor, protocol specific
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethoxyamineDrug
Also called NSC-3801, MX
For all cycles, TMZ will be given orally for 5 days every 28 days. MX will be given as a single one-hour IV infusion every 28 days. Temozolomide will be administered within 5 minutes following the initiation of methoxyamine.
TemozolomideDrug
Also called TMZ
Patients receive oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Non-CNS Disease | Experimental | A traditional 3 + 3 dose escalation design will be implemented. Successive cohorts of participants (3 participants/cohort) will be entered sequentially to each dose level. If 0/3 participants at a dose level experience dose limiting toxicity (DLT) new participants may be entered at the next higher dose level. If 1 participant has a DLT, 3 more will be enrolled at the same dose level. If the 1st participant in the expanded cohort (4th at the given DL), experiences no DLT, the remaining 2 participants can start treatment. If 2 or more experience DLT in the first cycle, no further participants are started at that dose and the MTD is the highest dose level in which <2 (of 6) participants develop DLT. If the final dose level is deemed the MTD, 6 participants will be treated at this dose level even if a DLT has not been observed. Receives: Drug: Methoxyamine; Drug: Temozolomide |
| CNS Disease | Experimental | A traditional 3 + 3 dose escalation design with successive cohorts of 3 participants will be entered sequentially to each dose level. If 0/3 participants experience DLT, new participants may be entered at the next higher dose level. If 1 participant has a DLT, 3 more will be enrolled at the same dose level. If the 1st participant in the expanded cohort (4th at the given DL), experiences no DLT, the remaining 2 participants can start treatment. If 1/3 participants experience a non-CNS DLT in Cohort B dose level 6, dose escalation will continue to dose level 7, as 3 subjects have already been treated in Cohort A dose level 6 and 7 subjects in Cohort A dose level 7, none of whom experienced non-CNS toxicities. If 2 or more experience DLT in cycle 1, no more participants are started at that dose and the MTD is the highest dose where <2/6 participants develop DLT. If the final dose level is deemed the MTD, 6 participants will be treated at this dose level even if no DLT has been observed. Receives: Drug: Methoxyamine; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of methoxyamine
A total of 38 patients were analyzed to determine the maximum tolerated dose of methoxyamine in this study and this was determined in the non-CNS arm. An initial 6 patients received treatment with continuous dosing of methoxyamine and based on an assessment of pharmacokinetics, in this group, the study was revised to administer methoxyamine as a bolus dose. Thirty-eight patients received this type of dosing.
Measured: Courses repeat every 28 days in the absence of unacceptable toxicity.
Dose limiting toxicities of the combination of methoxyamine and temozolomide
The 38 patients receiving bolus dosing of methoxyamine in this trial were used to determine any dose limiting toxicities.
Measured: Courses repeat every 28 days in the absence of unacceptable toxicity.
Pharmacokinetics methoxyamine and temozolomide, when given alone or in combination
Thirty-eight patients were analyzed per the schedule above (after an initial 6 patients treated per an alternative dosing schedule).
Measured: Blood sampling during cycles 1 and 2 depending upon the PK data from initial subjects.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2009 (estimated)
- Study start16 Aug 2007
- Primary completion8 Mar 2017
- Study completion8 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jennifer Eads, MD, Principal investigator, University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00892385
- Sponsor's protocol ID
- CASE1Y05
- Other IDs
- P30CA043703, CASE1Y05, WIRB-20070151, NCI-2009-01286
- Status last verified
- Feb 2019
- First submitted
- 1 May 2009
- Last updated
- 22 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Methoxyamine and Temozolomide in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00892385
- Acronym / sponsor ID
- CASE1Y05
- Keywords
- unspecified adult solid tumor, protocol specific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 16 Aug 2007 (actual)
- Primary completion
- 8 Mar 2017 (actual)
- Study completion
- 8 Mar 2017 (actual)
- First posted
- 4 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-CNS Disease | Experimental | Drug: Methoxyamine, Drug: TemozolomideA traditional 3 + 3 dose escalation design will be implemented. Successive cohorts of participants (3 participants/cohort) will be entered sequentially to each dose level. If 0/3 participants at a dose level experience dose limiting toxicity (DLT) new participants may be entered at the next higher dose level. If 1 participant has a DLT, 3 more will be enrolled at the same dose level. If the 1st participant in the expanded cohort (4th at the given DL), experiences no DLT, the remaining 2 participants can start treatment. If 2 or more experience DLT in the first cycle, no further participants are started at that dose and the MTD is the highest dose level in which <2 (of 6) participants develop DLT. If the final dose level is deemed the MTD, 6 participants will be treated at this dose level even if a DLT has not been observed. |
| CNS Disease | Experimental | Drug: Methoxyamine, Drug: TemozolomideA traditional 3 + 3 dose escalation design with successive cohorts of 3 participants will be entered sequentially to each dose level. If 0/3 participants experience DLT, new participants may be entered at the next higher dose level. If 1 participant has a DLT, 3 more will be enrolled at the same dose level. If the 1st participant in the expanded cohort (4th at the given DL), experiences no DLT, the remaining 2 participants can start treatment. If 1/3 participants experience a non-CNS DLT in Cohort B dose level 6, dose escalation will continue to dose level 7, as 3 subjects have already been treated in Cohort A dose level 6 and 7 subjects in Cohort A dose level 7, none of whom experienced non-CNS toxicities. If 2 or more experience DLT in cycle 1, no more participants are started at that dose and the MTD is the highest dose where <2/6 participants develop DLT. If the final dose level is deemed the MTD, 6 participants will be treated at this dose level even if no DLT has been observed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethoxyamineAlso: NSC-3801, MXFor all cycles, TMZ will be given orally for 5 days every 28 days. MX will be given as a single one-hour IV infusion every 28 days. Temozolomide will be administered within 5 minutes following the initiation of methoxyamine. | Drug | CNS Disease, Non-CNS Disease |
| TemozolomideAlso: TMZPatients receive oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug | CNS Disease, Non-CNS Disease |
Primary outcome
Maximum tolerated dose of methoxyamine
Time frame: Courses repeat every 28 days in the absence of unacceptable toxicity.
A total of 38 patients were analyzed to determine the maximum tolerated dose of methoxyamine in this study and this was determined in the non-CNS arm. An initial 6 patients received treatment with continuous dosing of methoxyamine and based on an assessment of pharmacokinetics, in this group, the study was revised to administer methoxyamine as a bolus dose. Thirty-eight patients received this type of dosing.
Dose limiting toxicities of the combination of methoxyamine and temozolomide
Time frame: Courses repeat every 28 days in the absence of unacceptable toxicity.
The 38 patients receiving bolus dosing of methoxyamine in this trial were used to determine any dose limiting toxicities.
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.
Thirty-eight patients were analyzed per the schedule above (after an initial 6 patients treated per an alternative dosing schedule).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Eads, MD principal investigator
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methoxyamine and Temozolomide in people with Unspecified Adult Solid Tumor, Protocol Specific, run by Case Comprehensive Cancer Center 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 14 inclusion and 7 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: finished, as of the sponsor's last update on 22 Feb 2019. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose of methoxyamine (time frame: Courses repeat every 28 days in the absence of unacceptable toxicity.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Feb 2019.