Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer

NCT01365910 | Terminated Phase 2 Results DMC

• 2 other identifiers: VICC GI 1058NCI-2011-00833
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well Linifanib works in treating patients with advanced, refractory colorectal cancer expressing k-Ras mutations. Linifanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15%

  Per Response Evaluation in Solid Tumors (RECIST) criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) \> 30% decrease in the sum of the longest diameter (LD) of target lesions, progressive disease (PD) \> 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions. Defined as the CR + PR recorded from the start of the treatment until disease progression/recurrence, the exact two-sided 95% confidence intervals will be reported.

  Baseline and every 8 weeks, up to 2 years

Secondary Outcomes (3)

• Progression-free Survival

  Every 3 months, up to 2 years

• Overall Survival

  Every 3 months, up to 2 years

• Number of Patients With Each Worst-Grade Toxicity

  date on-study up to 2 years following final dose of study

Study Arms (1)

Treatment (enzyme inhibitor)

EXPERIMENTAL

Patients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: linifanib

Interventions

linifanib DRUG

Given PO

Also known as: ABT-869, multitargeted receptor tyrosine kinase inhibitor ABT-869

Treatment (enzyme inhibitor)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed colorectal cancer refractory to at least 1 but no more than 3 systemic chemotherapy regimens
• Patients must have received one standard chemotherapy regimen in the metastatic setting
• Established Ras-mutant tumor status (archived specimens are okay and this test can have been performed at local laboratories)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• The subject must have adequate bone marrow and organ function, defined as follows:
• Hemoglobin ≥ 9g/dL
• Platelets \>100,000,
• Absolute neutrophil count (ANC) \> 1000/uL,
• Serum creatinine \< 1.5 x upper limit of normal,
• Total bilirubin \< 1.5 x the upper limit of normal,
• AST and ALT ≤ 2.0 x upper limit of normal (or ≤ 5 x ULN in the presence of liver metastases)
• Measurable disease, defined as at least 1 unidimensionally measurable lesion on a computed tomography (CT) scan or magnetic resonance imaging (MRI) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 7 days of study treatment; surgically sterile and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-child-bearing potential
• Female subjects of child-bearing potential and male subjects must agree to use adequate contraception prior to study entry, for the duration of study participation and up to two months after the last dose of ABT 869; adequate contraception methods should be used consistently and correctly and include the following:
• Total abstinence from sexual intercourse (minimum one complete menstrual cycle)

You may not qualify if:

• Untreated central nervous system (CNS) metastases; patients may have CNS metastases from any timeframe as long as they are treated and not progressing; brain imaging is not required if there is no clinical suspicion of brain metastases
• Pregnant or lactating females are excluded
• Uncontrolled hypertension defined as systolic blood pressure (BP) \> 140 and/or diastolic BP \> 90 initially evaluated on day of study eligibility determination (when laboratory parameters are assessed), but must be maintained on day of study initiation; (If a patient is found to have a value outside the range above, repeat BP may be assessed and if at subsequent readings x 2 (taken in clinic at least 15 minutes apart) criteria are met, the patient can then be eligible; initiation or modification of antihypertensives is allowed to achieve adequate BP for eligibility; finally, in the case that subsequent determinations are required, the BP assessment that counts towards eligibility is the reading on the day of study initiation); (note: a clinic BP reading without the patient having been at rest for 15 minutes or with the wrong cuff size can be repeated the same day for eligibility criteria to be determined
• Active bleeding or history of bleeding from cancer related events
• History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) or recent myocardial infarction (MI) (\< 6 months)
• Active ulcerative colitis, Crohn's disease or Celiac disease that could interfere with the absorption of the drug
• Current use of therapeutic anticoagulation; low dose anticoagulation for catheter prophylaxis is permitted; Lovenox is permitted for prophylaxis; (Note: patients who develop thrombosis and are placed on anticoagulation while on this trial may continue on study at the discretion of the investigator)
• The subject has had major surgery within 28 days of Study Day 1
• The subject has had radiation therapy within 14 days of Study Day 1
• The subject had prior bevacizumab within 28 days of study day 1
• No prior treatment with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors; prior treatment with other investigational agents is allowed
• The subject has a medical condition, which in the opinion of the study investigator, places them at unacceptably high risk for toxicities
• Other active malignancy for which the patient has been treated within the past one year
• Subjects with known human immunodeficiency virus (HIV) infection are excluded
• Subject has documented left ventricular ejection fraction (LVEF) \< 50%

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead

Study Sites (2)

Vanderbilt Cool Springs

Franklin, Tennessee, 37067, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

Related Links

• Vanderbilt-Ingram Cancer Center, Find a Clnical Trial

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

linifanib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Dr. Jordan Berlin
• Organization: Vanderbilt-Ingram Cancer Center

jordan.berlin@vanderbilt.edu

615-343-4128

Study Officials

• Jordan Berlin, MD

  Vanderbilt-Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine; Clinical Director, GI Oncology Program; Director, Phase I Program; Medical Director, Clinical Trials Shared Resources; Medical Oncologist

Study Record Dates

• First Submitted: June 1, 2011
• First Posted: June 3, 2011
• Study Start: June 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2013
• Last Updated: August 26, 2014
• Results First Posted: August 26, 2014

Record last verified: 2014-08

Locations

US (2)