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Recurrent Colon CancerPhase 2NCT01365910

Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer

A Phase 2 study testing linifanib in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by Vanderbilt-Ingram Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
linifanib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesUnited States
Study dates
Jun 2011to Jun 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • A vasectomized partner
  • Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
  • Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
  • The subject must be willing and able to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations
  • The subject must have given written informed consent prior to the initiation of any screening or study-specific procedures
  • Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study-specific procedures
  • Patients must be at least 14 days status post last day of prior chemotherapy (at least 28 days since last dose of bevacizumab) and have recovered to grade =< 1 from all chemotherapy-associated side effects
  • Patients must have the ability to swallow pills

Who cannot join

  • 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
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  • 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%
  • Subject has Proteinuria > grade 1 at baseline measured by urine dipstick (2+ or greater) and confirmed by 24 hour (hr) urine collection (> = 1g/24hrs)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Vanderbilt Cool Springs

    Franklin, Tennessee, 37067

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232-6838

Other trials in United States

About this study

Official title: An Investigator Initiated, Phase II Study of Linifanib in Patients With Advanced, Refractory Colorectal Cancer Expressing Mutated kRas

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To achieve an overall response rate of 15% or more.

SECONDARY OBJECTIVES:

  1. Determine progression free survival. II. Determine overall survival. III. Evaluate toxicity profile of ABT 869 (linifanib) in this patient population.

OUTLINE:

Patients receive Linifanib orally (PO) once daily (QD). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

Being tested
linifanib
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • linifanibDrug

    Also called ABT-869, multitargeted receptor tyrosine kinase inhibitor ABT-869

    Given PO

Study groups in NCT01365910
Study groupRoleWhat they receive
Treatment (enzyme inhibitor)ExperimentalPatients receive linifanib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: linifanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and every 8 weeks, up to 2 years

Secondary outcomes (3)

  1. Progression-free Survival

    Estimated probable duration of life without disease progression, from on-study date to earlier of progression date or date of death from any cause, using the Kaplan-Meier method with censoring. Disease progression is defined under RECIST v1.1 as >=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions.

    Measured: Every 3 months, up to 2 years

  2. Overall Survival

    Estimated probable duration of life from on-study date to date of death from any cause, using the Kaplan-Meier method with censoring.

    Measured: Every 3 months, up to 2 years

  3. Number of Patients With Each Worst-Grade Toxicity

    Count of patients according to the worst-grade toxicity experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: grade 1= mild; grade 2 = moderate; grade 3 = severe; grade 4 = life-threatening; grade 5 = death

    Assessed: days 1 \&15 of cycle 1; day 1 of each subsequent 28-day cycle; at 30-day follow-up for two years

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2011 (estimated)
  2. Study startJun 2011
  3. Primary completionMay 2012
  4. Study completionJun 2013

Why it stopped: Interim analysis determined the study did not meet criteria to proceed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01365910
Sponsor's protocol ID
VICC GI 1058
Other IDs
NCI-2011-00833
Status last verified
Aug 2014
First submitted
1 Jun 2011
Last updated
26 Aug 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing linifanib in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by Vanderbilt-Ingram Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15% (time frame: Baseline and every 8 weeks, up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01365910.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2014.

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