- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00101244
SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma
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 Overview
Status
Conditions
- 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 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
- Splenic Marginal Zone Lymphoma
- Waldenström Macroglobulinemia
- Unspecified Adult Solid Tumor, Protocol Specific
- Recurrent Adult Grade III Lymphomatoid Granulomatosis
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Small Lymphocytic 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 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
- Adult Grade III Lymphomatoid Granulomatosis
- Stage IV Adult Immunoblastic Large Cell Lymphoma
- Stage IV Adult Lymphoblastic Lymphoma
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- Barbara Ann Karmanos Cancer Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (ispinesib)
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. |
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Up to 21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
|
Up to 6 years
|
Plasma ispinesib concentration levels
Time Frame: Up to day 24
|
Descriptive statistics will be computed, including both point and confidence interval estimates.
|
Up to day 24
|
Pre- and post-treatment intra-tumoral drug levels (from tumor-accessible, consenting patients only)
Time Frame: Up to day 3
|
Descriptive statistics will be computed, including both point and confidence interval estimates.
|
Up to day 3
|
Cluster of differentiation (CD)34+ stem cell levels
Time Frame: Pre-treatment
|
Descriptive statistics will be computed, including both point and confidence interval estimates.
|
Pre-treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Patricia LoRusso, Barbara Ann Karmanos Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Precancerous Conditions
- Leukemia, Lymphoid
- Leukemia
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Lymphoma, T-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Hodgkin Disease
- Recurrence
- Lymphoma, Non-Hodgkin
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphomatoid Granulomatosis
- Lymphoma, Extranodal NK-T-Cell
Other Study ID Numbers
- NCI-2012-03193
- U01CA062487 (U.S. NIH Grant/Contract)
- C-2818
- CDR0000404369 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAnn Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Ann Arbor Stage I Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Extranodal Marginal Zone LymphomaUnited States
-
University of WashingtonGenentech, Inc.RecruitingMarginal Zone Lymphoma | Non-Hodgkin Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular Lymphoma | Indolent B-Cell Non-Hodgkin Lymphoma | Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Refractory Extranodal Marginal Zone...United States
-
Narendranath EpperlaNot yet recruitingRecurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory Mantle Cell Lymphoma | Refractory Marginal Zone Lymphoma | Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid... and other conditionsUnited States
-
University of WashingtonMillennium Pharmaceuticals, Inc.Active, not recruitingFollicular Lymphoma | Waldenstrom Macroglobulinemia | Mantle Cell Lymphoma | Marginal Zone Lymphoma | Chronic Lymphocytic Leukemia | Lymphoplasmacytic Lymphoma | Small Lymphocytic Lymphoma | Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Refractory Extranodal Marginal...United States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Genentech, Inc.; Pharmacyclics LLC.RecruitingNon-Hodgkin's Lymphoma | Indolent Non-hodgkin Lymphoma | Ann Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Ann Arbor Stage II Follicular Lymphoma | Ann Arbor Stage II Nodal Marginal Zone Lymphoma | Ann Abor Stage III B-Cell Non-Hodgkin Lymphoma | Ann Arbor... and other conditionsUnited States
-
Yazeed SawalhaWithdrawnRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Grade 3a Follicular Lymphoma | Refractory Grade 1 Follicular... and other conditions
-
Robert LowskyNational Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Splenic Marginal Zone Lymphoma | Recurrent Small Lymphocytic...United States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Waldenstrom Macroglobulinemia | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma and other conditionsUnited States
-
Arbeitsgemeinschaft medikamentoese TumortherapieHoffmann-La Roche; LipomedCompletedLymphoma of Mucosa-Associated Lymphoid TissueAustria
-
National Cancer Institute (NCI)WithdrawnExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Splenic Marginal Zone LymphomaUnited States
Clinical Trials on laboratory biomarker analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States