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Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT02277093
Recruitment Status : Terminated (FDA issued a clinical hold as pacritinib had increased side effects)
First Posted : October 28, 2014
Results First Posted : May 1, 2017
Last Update Posted : May 1, 2017
Sponsor:
Collaborator:
CTI BioPharma
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE October 24, 2014
First Posted Date  ICMJE October 28, 2014
Results First Submitted Date  ICMJE March 16, 2017
Results First Posted Date  ICMJE May 1, 2017
Last Update Posted Date May 1, 2017
Actual Study Start Date  ICMJE September 22, 2015
Actual Primary Completion Date March 31, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2017)
Progression-free Survival (PFS) [ Time Frame: Through completion of follow-up (median follow-up was 6.61 months) ]
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression - at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Original Primary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
Progression-free Survival (PFS) [ Time Frame: 4 months ]
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression - at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2017)
  • Toxicity Profile and Tolerability as Measured by Reportable Adverse Events [ Time Frame: Up to 28 days following last day of study treatment ]
    • The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
    • Reportable adverse events will be tracked for 28 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events that are greater than or equal to grade 2 and are considered possibly, probably, or definitely related to study treatment.
  • Overall Response Rate (ORR) [ Time Frame: Through completion of follow-up (median follow-up was 6.61 months) ]
    • The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
    • Using RECIST 1.1
    • The follow-up time was calculated from the start of treatment until death or on the final collection date of data on 10/27/2016.
  • Time to Progression (TTP) [ Time Frame: Through completion of follow-up (median follow-up was 6.61 months) ]
  • Overall Survival (OS) [ Time Frame: Through completion of follow-up (median follow-up was 6.61 months) ]
    -The follow-up time for OS was calculated from the start of treatment until death or on the final collection date of data on 10/27/2016.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
  • Toxicity profile and tolerability [ Time Frame: 5 months (estimated median PFS of 4 months) ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting. Reportable adverse events will be tracked for 28 days following the last day of study treatment. For the purposes of this protocol, reportable adverse events are events that are greater than or equal to grade 2 and are considered possibly, probably, or definitely related to study treatment.
  • Overall Response Rate (ORR) [ Time Frame: 12 months (estimated as there is no limit to follow-up) ]
    The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Using RECIST 1.1
  • Time to Progression (TTP) [ Time Frame: 12 months (estimated as there is no limit to follow-up) ]
  • Overall Survival (OS) [ Time Frame: 12 months (estimated as there is no limit to follow-up) ]
  • Correlate cytokine levels (IL-6 & IL-8) with clinical outcomes [ Time Frame: 4 months (estimated median PFS of 4 months) ]
    Correlative studies will be drawn on Cycle 1 Day 1 and Day 28
  • Measure of inflammation (using serum C-reactive protein) [ Time Frame: 4 months (estimated median PFS of 4 months) ]
    Correlate serum C-reactive protein (CRP) as a measure of inflammation with clinical outcomes. Correlative studies will be drawn on Cycle 1 Day 1 and Day 28
  • Measure of inflammation (using modified Glasgow Prognostic Score) [ Time Frame: 4 months (estimated median PFS of 4 months) ]
    Correlate the modified Glasgow Prognostic Score (mGPS) as a measure of inflammation with clinical outcomes.
  • Correlate microRNA serum levels (miR221) with clinical outcomes [ Time Frame: 4 months (estimated median PFS of 4 months) ]
    Correlative studies will be drawn on Cycle 1 Day 1 and Day 28
  • Correlate tobacco smoking status with clinical outcomes [ Time Frame: 4 months (estimated median PFS of 4 months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer
Official Title  ICMJE Phase II Study With Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer
Brief Summary The investigators propose to assess the efficacy, progression-free survival, and adverse events of pacritinib in patients with refractory colorectal cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE Drug: Pacritinib
Other Name: SB1518
Study Arms  ICMJE Experimental: Pacritinib
  • Pacritinib is an oral drug which will be taken on an outpatient basis daily on a 28-day cycle at a dose of 200 mg twice a day (BID)
  • Pacritinib should be take at approximately the same times every day with a glass of water, with or without food
Intervention: Drug: Pacritinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 9, 2016)
11
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2014)
38
Actual Study Completion Date  ICMJE October 27, 2016
Actual Primary Completion Date March 31, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed refractory colorectal cancer
  • Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam.
  • Refractory to or intolerant of standard systemic therapy, including having received two or more standard available therapies known to prolong survival for which s/he was eligible, including FOLFOX or FOLFIRI with or without bevacizumab, aflibercept, cetuximab, or panitumumab
  • At least 18 years of age.
  • ECOG performance status < 2
  • Life expectancy ≥ 12 weeks.
  • Normal bone marrow and organ function as defined below:

    • Absolute neutrophil count ≥ 1,500/mcl
    • Platelets ≥ 50,000/mcl
    • Total bilirubin ≤ 2.0 x IULN
    • AST (SGOT) / ALT (SGPT) ≤ 3.0 x IULN
    • Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above 2.0 mg/dL
    • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
    • Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

  • Prior therapy with a JAK2 or FLT3 inhibitor.
  • A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
  • Received any chemotherapeutic or targeted agent for metastatic colorectal cancer within two weeks of initiation of study drug.
  • Currently receiving any other investigational agents.
  • Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
  • Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with pacritinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  • Use of potent cytochrome P450 3A4 (CYP3A4) inhibitor within one week of pacritinib initiation.
  • Patients with CTCAE grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety. Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade ≥ 3, corrected QT interval (QTc) prolongation >450ms, or other factors that increase the risk for QT interval prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome).
  • Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral medication such as ongoing grade 3 or higher diarrhea, constipation, nausea, or vomiting.
  • Active viral hepatitis.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02277093
Other Study ID Numbers  ICMJE 201412087
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE CTI BioPharma
Investigators  ICMJE
Principal Investigator: Benjamin R Tan, M.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP