Adult Grade III Lymphomatoid GranulomatosisPhase 1NCT00101244
SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma
A Phase 1 study testing ispinesib, laboratory biomarker analysis and pharmacological study in people with Adult Grade III Lymphomatoid Granulomatosis and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of SB-715992 in treating patients with metastatic or unresectable solid tumors or Hodgkin's or non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Grade III Lymphomatoid Granulomatosis, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma
- What is being tested?
- ispinesib, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2004to Feb 2010
- 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 histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; patients with solid hematologic malignancies (Hodgkin's and non-Hodgkin's lymphomas) may be included as long as a bone marrow has been performed within 6 weeks of enrollment
- Prior chemotherapy is allowed; patients may not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have full recovery from the acute effects of any prior chemotherapy; patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to initiation of study treatment
- Prior radiation therapy is allowed; patients must have completed radiation at least 4 weeks prior to initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
- Prior treatment with EGFR inhibitors is allowed; prior experimental therapies (non FDA-approved agents) and immunotherapies are allowed; patients may not have received these therapies for 4 weeks prior to the initiation of study treatment and must have a full recovery from the acute effects of these therapies
- ECOG performance status =< 2 (Karnofsky >= 60%)
- Life expectancy of > 12 weeks
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- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Total bilirubin =< normal institutional limits
- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- Creatinine =< 1.5 X institutional upper limit of normal OR creatinine clearance (calculated) or measured clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- The effects of SB-715992 on the developing human fetus are unknown; for this reason and because mitotic inhibitors are known to be teratogenic, 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 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 acute AEs due to agents administered more than 4 weeks earlier
- Patients may not have received any other investigational agents within 28 days of study entry
- Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but potentially may have anticancer effect (i.e. megestrol acetate, bisphosphonates); these medications must have been started 1 month prior to enrollment on study; in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing- releasing hormone agonists
- Prohibited medications: SB-715992 is a moderate to significant in vitro inhibitor of CYP3A4; the following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may alter study drug exposure; the use of these medications/substances within 14 days (>= 6 months for amiodarone) prior to the administration of the first dose of SB-715992 through discontinuation from the study is prohibited;
- Inhibitors of CYP3A4
- Antibiotics: clarithromycin, erythromycin, troleandomycin
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- Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day), voriconazole
- Antidepressants: nefazodone, fluovoxamine
- Calcium channel blockers: verapamil, diltiazem
- Bitter Orange
- Miscellaneous: amiodarone*, grapefruit juice; *use of amiodarone within 6 months prior to the administration of the first dose of SB-715992 is prohibited; use of grapefruit juice within 7 days prior to administration of the first dose of SB-715992 is prohibited
- Inducers of CYP3A4
- Anticonvulsants: phenytoin, carbamazepine, phenobarbital
- Antibiotics: rifampin, rifabutin, rifapentine
- Miscellaneous: St. John's wort, modafinil, oxcarbazepine
- Patients with known, symptomatic or untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- 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 SB-715992 is a mitotic inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SB-715992, breastfeeding should be discontinued if the mother is treated with SB-715992
- Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with SB-715992; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- Patients are ineligible for participation in the Drug Interaction study, or can be deemed to be ineligible to receive certain drug probes, if they have:
- Sensitivity to sulfa drugs or adverse reactions to sulfonylureas
- Concurrent antifungal medications, or within the past 4 weeks
- Diabetes or other glucose imbalance
- Acidosis
- Concurrent alcohol use (based on the discretion of treating physician)
- Concurrent phenytoin or diazepam treatment, or within the past 4 weeks
- Previous intolerance to benzodiazepam therapies
- A patient maybe excluded from all or a portion of the Drug Interaction study based on the medical discretion of the investigator
- EVEN THOUGH PATIENTS MAY BE INELIGIBLE TO PARTICIPATE IN THE DRUG INTERACTION STUDY, THEY CAN STILL PARTICIPATE IN THE PHASE I CLINICAL TRIAL
Trial locations and contacts
1 site in 1 country.
United States1 site
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
About this study
Official title: A Phase I, Open-Label, Dose-Escalation Study of SB-715992 Administered Days 1-3 of a 21-Day Cycle in Patients With Solid Tumors
This phase I trial is studying the side effects and best dose of SB-715992 in treating patients with metastatic or unresectable solid tumors or Hodgkin's or non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as SB-715992, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability of SB-715992 administered as a 1-hr intravenous infusion on days 1-3 of a 21-day cycle in patients with solid tumors.
II. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of SB-715992 for this administration schedule.
SECONDARY OBJECTIVES:
- To observe clinical response of SB-715992 given days 1-3, every 21-days. II. To characterize the pharmacokinetics (PK) of SB-715992 for this administration schedule.
III. To explore drug metabolism, molecular and cellular predictors of efficacy (biomarkers) and toxicity and drug interaction potential.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive SB-715992 IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SB-715992 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. Up to 10 additional patients are treated at the MTD
Patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 18-31 patients will be accrued for this study within 11-19 months.
- Conditions
- Adult Grade III Lymphomatoid Granulomatosis, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma
- Being tested
- ispinesib, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ispinesibDrug
Also called CK0238273, SB-715992
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ispinesib) | Experimental | Patients receive SB-715992 IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SB-715992 until the 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. Up to 10 additional patients are treated at the MTD. Receives: Drug: ispinesib; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Measured: Up to 21 days
Secondary outcomes (4)
Clinical response (complete response [CR], partial response [PR], and response duration) based on the Response Evaluation Criteria in Solid Tumors (RECIST)
Both point and confidence interval estimates of response rate will be calculated for all eligible patients (the intention to treat population), and for response-evaluable patients (the per-protocol population). Response duration will be calculated using the standard Kaplan-Meier estimator for a censored time-to-event endpoint.
Measured: Up to 6 years
Plasma ispinesib concentration levels
Descriptive statistics will be computed, including both point and confidence interval estimates.
Measured: Up to day 24
Pre- and post-treatment intra-tumoral drug levels (from tumor-accessible, consenting patients only)
Descriptive statistics will be computed, including both point and confidence interval estimates.
Measured: Up to day 3
Cluster of differentiation (CD)34+ stem cell levels
Descriptive statistics will be computed, including both point and confidence interval estimates.
Measured: Pre-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2005 (estimated)
- Study startNov 2004
- Primary completionFeb 2010
Why it stopped: Administratively Complete.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Grade III Lymphomatoid GranulomatosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Patricia LoRusso, Principal investigator, Barbara Ann Karmanos Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00101244
- Sponsor's protocol ID
- NCI-2012-03193
- Other IDs
- C-2818, U01CA062487, CDR0000404369
- Status last verified
- Jan 2013
- First submitted
- 7 Jan 2005
- Last updated
- 14 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Label, Dose-Escalation Study of SB-715992 Administered Days 1-3 of a 21-Day Cycle in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT00101244
- Acronym / sponsor ID
- NCI-2012-03193
- Conditions
- Adult Grade III Lymphomatoid Granulomatosis, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administratively Complete.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2004
- Primary completion
- Feb 2010 (actual)
- First posted
- 10 Jan 2005 (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.
This phase I trial is studying the side effects and best dose of SB-715992 in treating patients with metastatic or unresectable solid tumors or Hodgkin's or non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as SB-715992, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability of SB-715992 administered as a 1-hr intravenous infusion on days 1-3 of a 21-day cycle in patients with solid tumors.
II. To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of SB-715992 for this administration schedule.
SECONDARY OBJECTIVES:
- To observe clinical response of SB-715992 given days 1-3, every 21-days. II. To characterize the pharmacokinetics (PK) of SB-715992 for this administration schedule.
III. To explore drug metabolism, molecular and cellular predictors of efficacy (biomarkers) and toxicity and drug interaction potential.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive SB-715992 IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SB-715992 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. Up to 10 additional patients are treated at the MTD
Patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 18-31 patients will be accrued for this study within 11-19 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ispinesib) | Experimental | Drug: ispinesib, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive SB-715992 IV over 1 hour on days 1-3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SB-715992 until the 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. Up to 10 additional patients are treated at the MTD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; patients with solid hematologic malignancies (Hodgkin's and non-Hodgkin's lymphomas) may be included as long as a bone marrow has been performed within 6 weeks of enrollment
- Prior chemotherapy is allowed; patients may not have received chemotherapy for 4 weeks prior to the initiation of study treatment and must have full recovery from the acute effects of any prior chemotherapy; patients must not have had nitrosoureas or mitomycin C for 6 weeks prior to initiation of study treatment
- Prior radiation therapy is allowed; patients must have completed radiation at least 4 weeks prior to initiation of study treatment; patients who have received prior radiation to 50% or more of their total marrow volume will be excluded
- Prior treatment with EGFR inhibitors is allowed; prior experimental therapies (non FDA-approved agents) and immunotherapies are allowed; patients may not have received these therapies for 4 weeks prior to the initiation of study treatment and must have a full recovery from the acute effects of these therapies
- ECOG performance status =< 2 (Karnofsky >= 60%)
Key exclusion criteria (29 listed)
- 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 acute AEs due to agents administered more than 4 weeks earlier
- Patients may not have received any other investigational agents within 28 days of study entry
- Patients may not receive any other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study except for medications that are prescribed for supportive care but potentially may have anticancer effect (i.e. megestrol acetate, bisphosphonates); these medications must have been started 1 month prior to enrollment on study; in addition, men receiving treatment for prostate cancer will be maintained at castrate levels of testosterone by continuation of luteinizing- releasing hormone agonists
- Prohibited medications: SB-715992 is a moderate to significant in vitro inhibitor of CYP3A4; the following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may alter study drug exposure; the use of these medications/substances within 14 days (>= 6 months for amiodarone) prior to the administration of the first dose of SB-715992 through discontinuation from the study is prohibited;
- Patients with known, symptomatic or untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
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 |
|---|---|---|
| ispinesibAlso: CK0238273, SB-715992Given IV | Drug | Treatment (ispinesib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (ispinesib) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (ispinesib) |
Primary outcome
Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time frame: Up to 21 days
4 secondary outcomes
Clinical response (complete response [CR], partial response [PR], and response duration) based on the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 6 years
Plasma ispinesib concentration levels
Time frame: Up to day 24
Pre- and post-treatment intra-tumoral drug levels (from tumor-accessible, consenting patients only)
Time frame: Up to day 3
Cluster of differentiation (CD)34+ stem cell levels
Time frame: Pre-treatment
Results and safety
The study was stopped early (reason given: Administratively Complete.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2013.
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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.
Patricia LoRusso principal investigator
Barbara Ann Karmanos Cancer Institute
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 ispinesib, laboratory biomarker analysis and pharmacological study in people with Adult Grade III Lymphomatoid Granulomatosis and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, 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 13 inclusion and 29 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 14 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?
Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 (time frame: Up to 21 days). 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 14 Jan 2013.