Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer

NCT00604721 | Completed Phase 2 Results

• 10 other identifiers: NCI-2009-0024707-097377782MCC-07-0973VU-VICC-GI-0726GCRC-2625-ORCMCC-15260CDR0000571751N01CM62207N01CM62208
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 6

Brief Summary

This phase II trial is studying selumetinib to see how well it works in treating patients with locally advanced or metastatic liver cancer. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth.

Conditions

Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Radiographic Objective Response (OR)

  To ascertain the objective response rate (Complete Response + Partial Response \[CR+PR\]) of patients with the single-agent AZD6244. Our study utilized Response Evaluation Criteria in Solid Tumors (RECIST) to evaluate response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  33 weeks

Secondary Outcomes (2)

• Median Progression Free Survival (PFS)

  33 weeks

• Median Overall Survival (OS)

  33 weeks

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

Patients receive a single dose of selumetinib on day 1 and undergo blood collection for PK sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Drug: selumetinib; Other: pharmacological study

Interventions

selumetinib DRUG

Given orally

Also known as: ARRY-142886, AZD6244

Treatment (enzyme inhibitor therapy)

pharmacological study OTHER

Also known as: pharmacological studies

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

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

You may qualify if:

• Meets 1 of the following criteria:
• Histologically or cytologically confirmed hepatocellular carcinoma
• Serum alpha fetoprotein \> 1000ng/dL with characteristic imaging findings coupled with the appropriate clinical scenario (i.e., chronic hepatitis and/or cirrhosis)
• Child's A or B cirrhosis allowed
• If Child's B cirrhosis is present, the patient may not have significant encephalopathy or ascites that requires paracentesis and must meet laboratory criteria (i.e., well-compensated Child's B)
• Metastatic disease (including any proven lymph node metastases) or localized disease not amenable to potentially curative transplant/locoregional/surgical therapy as determined by a qualified surgeon or tumor board
• Measurable disease, defined as at least one unidimensionally measurable ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• No known brain metastases
• ECOG performance status ≤ 2
• Life expectancy \> 3 months
• Leukocytes ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelets ≥ 75,000/mm³
• Total bilirubin \< 2 times upper limit of normal (ULN)
• AST/ALT \< 5 times ULN

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (6)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

The study was stopped at the interim analysis due to lack of radiographic response.

Results Point of Contact

• Title: Bert. H. O'Neil, Associate Professor, Clinical Research
• Organization: UNC Lineberger Comprehensive Cancer Center

bert_oneil@med.unc.edu

919-966-4431

Study Officials

• Bert O'Neil

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 30, 2008
• Study Start: November 1, 2007
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: May 28, 2014
• Results First Posted: September 6, 2012

Record last verified: 2013-05

Locations

US (6)