- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02049593
PARP Inhibitor BMN-673 and Temozolomide or Irinotecan Hydrochloride in Treating Patients With Locally Advanced or Metastatic Solid Tumors
Phase I Trial of BMN 673 and Selected Cytotoxics in Patients With Advanced Solid Tumors
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. To assess the safety and tolerability and to estimate the maximum tolerated dose (MTD) of the following combinations in participants with advanced solid tumors: Arm A: BMN 673 (PARP inhibitor BMN-673) and temozolomide; Arm B: BMN 673 and irinotecan (irinotecan hydrochloride).
SECONDARY OBJECTIVES:
I. To evaluate the pharmacokinetics of BMN 673, temozolomide, and irinotecan when BMN 673 is given in combination with temozolomide (Arm A) or irinotecan (Arm B). To assess the effects of temozolomide and irinotecan in Arms A and B respectively on the pharmacokinetics of BMN 673.
II. To evaluate biomarkers that correlate with effect of BMN 673 in combination with temozolomide or irinotecan.
III. To document any anti-tumor activity.
OUTLINE: This is a dose-escalation study of PARP inhibitor BMN-673. Patients are assigned to 1 of 2 treatment arms.
ARM A: Patients receive PARP inhibitor BMN-673 orally (PO) once daily (QD) on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 12 months.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- Jonsson Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST, v1.1)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT may be =< 5 x ULN
- Total serum bilirubin =< 1.5 x ULN
- Calculated creatinine clearance of >= 40 ml/min; as per Cockcroft-Gault formula
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelet count >= 100,000/mm^3
- Able to take oral medications
- Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
- Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 30 days after the last dose of BMN 673
- Females of childbearing potential must have a negative serum pregnancy test at screening
Exclusion Criteria:
- Has not recovered (recovery is defined as National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE version (v)4.03] grade =< 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion requirements stated in the inclusion criterion
- Prior treatment with a PARP inhibitor
- Prior allergic reaction or severe intolerance to either irinotecan or temozolomide
- History of central nervous system (CNS) metastasis that are untreated or not stable
- Any antitumor systemic cytotoxic therapies within 28 days prior to enrollment (6 weeks for nitrosoureas or mitomycin-C); prior high-dose chemotherapy with bone marrow or stem cell transplant is excluded
- Is known to have human immunodeficiency virus (HIV) or has active hepatitis C virus (HCV), or active hepatitis B virus (HBV)
- Has had major surgery within 28 days prior to enrollment
- Active gastrointestinal tract disease with malabsorption syndrome
- Requirement for IV alimentation
- Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
- Symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication (atrial fibrillation is permitted)
- Use of any investigational product or investigational medical device within 28 days prior to enrollment
Concurrent disease or condition that would interfere with study participation or safety, such as:
- Active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 by NCI CTCAE (v 4.03) within 14 days prior to enrollment
- Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
- Non-healing wound, ulcer, or bone fracture
- Bone marrow disorder including myelodysplasia
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (PARP inhibitor BMN-673, temozolomide)
Patients receive PARP inhibitor BMN-673 PO QD on days 1-28 and temozolomide PO daily on days1-5.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Correlative studies
Other Names:
Given PO
Other Names:
Given PO
Other Names:
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Experimental: Arm B (PARP inhibitor BMN-673, irinotecan hydrochloride)
Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride IV on days 1 and 15.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Correlative studies
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose Limiting Toxicity graded using the NCI CTCAE v. 4.03
Time Frame: Up to 28 days
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Up to 28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events graded by NCI CTCAE v. 4.03
Time Frame: Up to 12 months
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Characterized by type, frequency, severity, timing, seriousness, and relationship to study therapy.
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Up to 12 months
|
Levels of PARP inhibitory BMN 673
Time Frame: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
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Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
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levels of temozolomide
Time Frame: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
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Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
|
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Levels of irinotecan hydrochloride
Time Frame: Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
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Baseline, at 30 and 60 minutes, at 1.5, 2, 3, 4, 6, and 8 hours of day 1 of courses 1 and 2
|
|
Biomarker levels in blood and tumor tissue
Time Frame: Baseline and Cycle1 Day 21 for participants undergoing biopsy (expansion phase only)
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Baseline and Cycle1 Day 21 for participants undergoing biopsy (expansion phase only)
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Incidence of laboratory abnormalities graded by NCI CTCAE v. 4.03
Time Frame: Up to 12 months
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Characterized by type, frequency, severity, timing, seriousness and relationship to study therapy.
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Up to 12 months
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Objective tumor response assessed using RECIST v. 1.1
Time Frame: Up to 12 months
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Sum of partial responses plus complete responses.
The proportion of ever achieving a clinical response will be estimated, and an exact one-sided 90% confidence interval will be constructed to identify the likely range for the underlying tumor response rate.
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Up to 12 months
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Duration of response
Time Frame: Time of initial response until documented tumor progression, assessed up to 12 months
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The log rank test will be used to examine association between categorical markers and time to disease progression.
Cox-proportional hazards regression models will be used to correlate quantitative markers with time to disease progression.
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Time of initial response until documented tumor progression, assessed up to 12 months
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Progression-free survival
Time Frame: Time from enrollment until objective tumor progression or death, assessed up to 12 months
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Time from enrollment until objective tumor progression or death, assessed up to 12 months
|
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Overall survival (OS)
Time Frame: Time from randomization until death from any cause, up to 12 months
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Time from randomization until death from any cause, up to 12 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Zev Wainberg, Jonsson Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Neoplastic Processes
- Neoplasm Metastasis
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Temozolomide
- Irinotecan
- Poly(ADP-ribose) Polymerase Inhibitors
- Talazoparib
Other Study ID Numbers
- 13-001857
- NCI-2014-00048 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- TRIO-US GI-07 (Other Identifier: Jonsson Comprehensive Cancer Center)
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.
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