Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Pacritinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The investigators propose to assess the efficacy, progression-free survival, and adverse
      events of pacritinib in patients with refractory colorectal cancer.
    

Eligibility criteria:

        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.