Enzastaurin and Bevacizumab in Treating Patients With Locally Advanced or Metastatic Cancer

NCT00550927 | Completed Phase 1

• 5 other identifiers: 11182JHOC-J0688JHOC-NA_00004943CDR0000571514H6Q-MC-S029
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (9)

• 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

Interventions

bevacizumab BIOLOGICAL

enzastaurin hydrochloride DRUG

diagnostic laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Related Publications (1)

• 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.

  PMID: 22766773 DERIVED

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Connie Collins, BSN

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: October 22, 2007
• First Posted: October 30, 2007
• Study Start: November 1, 2006
• Primary Completion: March 1, 2010
• Study Completion: September 1, 2012
• Last Updated: May 15, 2013

Record last verified: 2012-06

Locations

US (1)