Colorectal Cancer
Conditions
Brief summary
The investigators propose to assess the efficacy, progression-free survival, and adverse events of pacritinib in patients with refractory colorectal cancer.
Interventions
DRUGPacritinib
Sponsors
CTI BioPharma
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | 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) | 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) | Through completion of follow-up (median follow-up was 6.61 months) | — |
| Overall Survival (OS) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Pacritinib |
|---|---|
| Age, Continuous | 63 years |
| Baseline c-reactive protein (CRP) | 12.1 mg/L |
| Primary Site of Cancer Left colon | 2 Participants |
| Primary Site of Cancer Rectal | 2 Participants |
| Primary Site of Cancer Right colon | 7 Participants |
| Prior lines of therapy for metastatic disease | 4 prior lines of therapy |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 11 |
| serious Total, serious adverse events | 4 / 11 |
Outcome results
Primary
Progression-free Survival (PFS)
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.
Time frame: Through completion of follow-up (median follow-up was 6.61 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pacritinib | Progression-free Survival (PFS) | 1.91 months |
Secondary
Overall Response Rate (ORR)
* 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 frame: Through completion of follow-up (median follow-up was 6.61 months)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pacritinib | Overall Response Rate (ORR) | Complete response | 0 Participants |
| Pacritinib | Overall Response Rate (ORR) | Partial response | 0 Participants |
| Pacritinib | Overall Response Rate (ORR) | Stable disease | 1 Participants |
| Pacritinib | Overall Response Rate (ORR) | Progressive disease | 6 Participants |
| Pacritinib | Overall Response Rate (ORR) | Not evaluable | 4 Participants |
Secondary
Overall Survival (OS)
-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.
Time frame: Through completion of follow-up (median follow-up was 6.61 months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pacritinib | Overall Survival (OS) | 6.61 months |
Secondary
Time to Progression (TTP)
Time frame: Through completion of follow-up (median follow-up was 6.61 months)
Population: Only patients who had their first measurement scans were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pacritinib | Time to Progression (TTP) | 1.73 months | Standard Deviation 0.26 |
Secondary
Toxicity Profile and Tolerability as Measured by Reportable Adverse Events
* 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.
Time frame: Up to 28 days following last day of study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Diarrhea | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Edema limbs | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Edema face | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Fatigue | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Localized edema | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Blood bilirubin increased | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Dyspnea | 1 adverse event |
| Pacritinib | Toxicity Profile and Tolerability as Measured by Reportable Adverse Events | Rash maculopapular | 1 adverse event |