search
Back to results

SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma

Primary Purpose

Adult Grade III Lymphomatoid Granulomatosis, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ispinesib
laboratory biomarker analysis
pharmacological study
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Grade III Lymphomatoid Granulomatosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 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 Exclusion Criteria: 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 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

Sites / Locations

  • Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (ispinesib)

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

Secondary Outcome Measures

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.
Plasma ispinesib concentration levels
Descriptive statistics will be computed, including both point and confidence interval estimates.
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.
Cluster of differentiation (CD)34+ stem cell levels
Descriptive statistics will be computed, including both point and confidence interval estimates.

Full Information

First Posted
January 7, 2005
Last Updated
January 11, 2013
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00101244
Brief Title
SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Why Stopped
Administratively Complete.
Study Start Date
November 2004 (undefined)
Primary Completion Date
February 2010 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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. 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: I. 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: I. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Splenic Marginal Zone Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (ispinesib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ispinesib
Other Intervention Name(s)
CK0238273, SB-715992
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Clinical response (complete response [CR], partial response [PR], and response duration) based on the Response Evaluation Criteria in Solid Tumors (RECIST)
Description
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.
Time Frame
Up to 6 years
Title
Plasma ispinesib concentration levels
Description
Descriptive statistics will be computed, including both point and confidence interval estimates.
Time Frame
Up to day 24
Title
Pre- and post-treatment intra-tumoral drug levels (from tumor-accessible, consenting patients only)
Description
Descriptive statistics will be computed, including both point and confidence interval estimates.
Time Frame
Up to day 3
Title
Cluster of differentiation (CD)34+ stem cell levels
Description
Descriptive statistics will be computed, including both point and confidence interval estimates.
Time Frame
Pre-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia LoRusso
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States

12. IPD Sharing Statement

Learn more about this trial

SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma

We'll reach out to this number within 24 hrs