Pacritinib to Inhibit JAK/STAT Signaling in Refractory Colorectal Cancer

NCT02277093 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 201412087
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Through completion of follow-up (median follow-up was 6.61 months)

Secondary Outcomes (4)

• Toxicity Profile and Tolerability as Measured by Reportable Adverse Events

  Up to 28 days following last day of study treatment

• Overall Response Rate (ORR)

  Through completion of follow-up (median follow-up was 6.61 months)

• 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)

Study Arms (1)

Pacritinib

EXPERIMENTAL

* 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

Drug: Pacritinib

Interventions

Pacritinib DRUG

Also known as: SB1518

Pacritinib

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• CTI BioPharma: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Please note that the study ended early due to the FDA issuing a clinical hold as pacritinib had increased side effects.

Results Point of Contact

• Title: Benjamin R. Tan
• Organization: Washington University School of Medicine

btan@wustl.edu

314-362-9915

Study Officials

• Benjamin R Tan, M.D.

  Washington University School of Medicine

  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: SPONSOR

Study Record Dates

• First Submitted: October 24, 2014
• First Posted: October 28, 2014
• Study Start: September 22, 2015
• Primary Completion: March 31, 2016
• Study Completion: October 27, 2016
• Last Updated: May 1, 2017
• Results First Posted: May 1, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)