Enzastaurin and Bevacizumab in Treating Patients With Locally Advanced or Metastatic Cancer
Primary Purpose
Unspecified Adult Solid Tumor, Protocol Specific
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
enzastaurin hydrochloride
diagnostic laboratory biomarker analysis
pharmacological study
Sponsored by
About this trial
This is an interventional treatment trial for Unspecified Adult Solid Tumor, Protocol Specific focused on measuring unspecified adult solid tumor, protocol specific
Eligibility Criteria
DISEASE CHARACTERISTICS:
- Histologic or cytologic diagnosis of locally advanced or metastatic cancer for which no preferable therapy exists
- Measurable or nonmeasurable disease
- No CNS metastases or a primary CNS tumor
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 12 weeks
- WBC count ≥ 3.0 × 10^9/L
- Absolute neutrophil count ≥ 1.5 × 10^9/L
- Platelet count ≥ 100 × 10^9/L
- Hemoglobin ≥ 10 g/dL (6.21 mmol/L)
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver metastases are present)
- AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)
- Serum creatinine < 1.5 times ULN
No proteinuria at baseline, as demonstrated by either of the following:
- Urine protein:creatinine ratio < 1.0 at screening
- Urine dipstick for proteinuria < 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline must undergo a 24-hour urine collection that demonstrates ≤ 1 g of protein in 24 hours to be eligible for study participation)
- No second primary malignancy that could affect compliance with the study or interpretation of the study results
- No concurrent serious systemic disorder (e.g., active infection, including HIV) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the study
- No known hypersensitivity to bevacizumab or enzastaurin hydrochloride, or to a component of either drug
- No prior bevacizumab-related toxicity requiring discontinuation, such as a thromboembolic event, hemorrhage, or serious hypertension
No clinically significant cardiac disease, in the opinion of the investigator, including any of the following:
- Myocardial infarction within the past 6 months
- Symptomatic angina pectoris
- Congestive heart failure not controlled by medications
- ECG abnormalities indicative of clinically significant cardiac disease
- No evidence of bleeding diathesis or coagulopathy
- No nonhealing cutaneous wound or gastrointestinal ulcer
- No history of or risk for abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No hemoptysis requiring medical attention within the past 3 months
- No known history of cerebrovascular accidents or transient ischemic attacks
- No clinically significant vascular or peripheral vascular disease
- No hypertension not controlled by medical management
- No history of hypertensive crisis or hypertensive encephalopathy
- No significant traumatic injury within the past 28 days
- Able to comply with study or study procedures
- Able to swallow tablets
- Exhibits compliance and geographic proximity that allow adequate follow-up
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
PRIOR CONCURRENT THERAPY:
- Recovered from prior therapy
- No prior participation in this study or any other study involving enzastaurin hydrochloride
- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
At least 4 weeks since prior radiotherapy, anticancer hormone therapy, or other investigational therapy
- Patients with hormone-refractory prostate cancer receiving luteinizing hormone-releasing hormone analogue therapy (leuprolide or goserelin) prior to study enrollment should continue therapy during study participation
- At least 6 weeks since prior bicalutamide
- At least 4 weeks since prior flutamide or nilutamide
- More than 10 days since prior and no concurrent aspirin > 325 mg/day
- More than 28 days since prior major surgery or open biopsy
- More than 7 days since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device
- No concurrent carbamazepine, phenobarbital, or phenytoin
- No concurrent systemic anticoagulation
- No concurrent chronic use of other nonsteroidal anti-inflammatory drugs
- No concurrent routine use of colony-stimulating factors
- No concurrent major surgery
- No other concurrent chemotherapy, radiotherapy, immunotherapy, or experimental medications
- No other concurrent antitumor therapy
Sites / Locations
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Outcomes
Primary Outcome Measures
Recommended phase II doses of enzastaurin hydrochloride and bevacizumab
Safety
Time to disease progression
Overall response rate (complete and partial response)
Duration of response
Duration of stable disease
ECOG performance status over time
Pharmacokinetics
Biomarker (GSK3β) analysis
Secondary Outcome Measures
Full Information
NCT ID
NCT00550927
First Posted
October 22, 2007
Last Updated
May 14, 2013
Sponsor
Eli Lilly and Company
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00550927
Brief Title
Enzastaurin and Bevacizumab in Treating Patients With Locally Advanced or Metastatic Cancer
Official Title
A Phase 1 Safety Evaluation of Oral Enzastaurin in Combination With Bevacizumab in Patients With Advanced/Metastatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Eli Lilly and Company
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
RATIONALE: Enzastaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Enzastaurin and bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving enzastaurin together with bevacizumab may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of enzastaurin and bevacizumab in treating patients with locally advanced or metastatic cancer.
Detailed Description
OBJECTIVES:
To determine the recommended phase II doses of enzastaurin hydrochloride and bevacizumab that may be safely administered to patients with locally advanced or metastatic malignancies.
To characterize the toxicities of enzastaurin hydrochloride and bevacizumab in these patients.
To document the antitumor activity of enzastaurin hydrochloride and bevacizumab in these patients.
To evaluate the pharmacokinetics of enzastaurin hydrochloride and bevacizumab in these patients.
To assess GSK3β as a biomarker relevant to enzastaurin hydrochloride and its correlation with clinical outcome in these patients.
OUTLINE: This is a dose-escalation study of enzastaurin hydrochloride and bevacizumab.
Patients receive oral enzastaurin hydrochloride once, twice, or three times daily on days 1-21 or days 1-28 and bevacizumab IV over 30-90 minutes on day 1 or days 1 and 15. Courses repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically during study for pharmacokinetic evaluation. Samples are also analyzed for biomarker (GSK3β) by ELISA.
After completion of study treatment, patients are followed for 30 days.
National Cancer Institute (NCI) registered this trial with Eli Lilly as sponsor. NCI did not update the record. In June 2012, NCI transferred the trial to Lilly's clinicaltrials.gov account and Lilly updated the record with the trial status and trial completion dates. This trial is not an applicable trial under Food and Drug Administration Amendments Act of 2007 (FDAAA).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unspecified Adult Solid Tumor, Protocol Specific
Keywords
unspecified adult solid tumor, protocol specific
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Type
Drug
Intervention Name(s)
enzastaurin hydrochloride
Intervention Type
Other
Intervention Name(s)
diagnostic laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Recommended phase II doses of enzastaurin hydrochloride and bevacizumab
Title
Safety
Title
Time to disease progression
Title
Overall response rate (complete and partial response)
Title
Duration of response
Title
Duration of stable disease
Title
ECOG performance status over time
Title
Pharmacokinetics
Title
Biomarker (GSK3β) analysis
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologic or cytologic diagnosis of locally advanced or metastatic cancer for which no preferable therapy exists
Measurable or nonmeasurable disease
No CNS metastases or a primary CNS tumor
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
WBC count ≥ 3.0 × 10^9/L
Absolute neutrophil count ≥ 1.5 × 10^9/L
Platelet count ≥ 100 × 10^9/L
Hemoglobin ≥ 10 g/dL (6.21 mmol/L)
Bilirubin ≤ 2 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 3 times ULN (5 times ULN if liver metastases are present)
AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)
Serum creatinine < 1.5 times ULN
No proteinuria at baseline, as demonstrated by either of the following:
Urine protein:creatinine ratio < 1.0 at screening
Urine dipstick for proteinuria < 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline must undergo a 24-hour urine collection that demonstrates ≤ 1 g of protein in 24 hours to be eligible for study participation)
No second primary malignancy that could affect compliance with the study or interpretation of the study results
No concurrent serious systemic disorder (e.g., active infection, including HIV) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the study
No known hypersensitivity to bevacizumab or enzastaurin hydrochloride, or to a component of either drug
No prior bevacizumab-related toxicity requiring discontinuation, such as a thromboembolic event, hemorrhage, or serious hypertension
No clinically significant cardiac disease, in the opinion of the investigator, including any of the following:
Myocardial infarction within the past 6 months
Symptomatic angina pectoris
Congestive heart failure not controlled by medications
ECG abnormalities indicative of clinically significant cardiac disease
No evidence of bleeding diathesis or coagulopathy
No nonhealing cutaneous wound or gastrointestinal ulcer
No history of or risk for abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No hemoptysis requiring medical attention within the past 3 months
No known history of cerebrovascular accidents or transient ischemic attacks
No clinically significant vascular or peripheral vascular disease
No hypertension not controlled by medical management
No history of hypertensive crisis or hypertensive encephalopathy
No significant traumatic injury within the past 28 days
Able to comply with study or study procedures
Able to swallow tablets
Exhibits compliance and geographic proximity that allow adequate follow-up
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
PRIOR CONCURRENT THERAPY:
Recovered from prior therapy
No prior participation in this study or any other study involving enzastaurin hydrochloride
At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
At least 4 weeks since prior radiotherapy, anticancer hormone therapy, or other investigational therapy
Patients with hormone-refractory prostate cancer receiving luteinizing hormone-releasing hormone analogue therapy (leuprolide or goserelin) prior to study enrollment should continue therapy during study participation
At least 6 weeks since prior bicalutamide
At least 4 weeks since prior flutamide or nilutamide
More than 10 days since prior and no concurrent aspirin > 325 mg/day
More than 28 days since prior major surgery or open biopsy
More than 7 days since prior core biopsy or other minor surgical procedure, excluding placement of a vascular access device
No concurrent carbamazepine, phenobarbital, or phenytoin
No concurrent systemic anticoagulation
No concurrent chronic use of other nonsteroidal anti-inflammatory drugs
No concurrent routine use of colony-stimulating factors
No concurrent major surgery
No other concurrent chemotherapy, radiotherapy, immunotherapy, or experimental medications
No other concurrent antitumor therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Connie Collins, BSN
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Facility Information:
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231-2410
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22766773
Citation
Nwankwo N, Zhang Z, Wang T, Collins C, Resta L, Ermisch S, Day J, Decker R, Kornberg L, Nicol S, Thornton D, Armstrong DK, Carducci MA. Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics. Invest New Drugs. 2013 Jun;31(3):653-60. doi: 10.1007/s10637-012-9850-6. Epub 2012 Jul 6.
Results Reference
derived
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Enzastaurin and Bevacizumab in Treating Patients With Locally Advanced or Metastatic Cancer
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