Clinical trial NCT01776307: A Study of BBI608 in Adult Patients With Advanced Colorectal Cancer
Official title: A Phase II Clinical Study of BBI608 in Adult Patients With Advanced Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: BBI608
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2013-01-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, multi-center, Phase 2 study of BBI608 in combination with cetuximab, panitumumab or capecitabine in patients with advanced colorectal cancer.

Detailed description: This is an open label, multi-center, Phase 2 study of BBI608 administered in combination with either cetuximab, or panitumumab, or capecitabine. A cycle will consist of daily and continuous oral administration of BBI608 for four weeks in combination with either cetuximab, or panitumumab, or capecitabine.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent must be obtained and documented according to International Conference on Harmonization (ICH), Good Clinical Practice(GCP), the local regulatory requirements, and permission to use private health information in accordance with the Health Insurance Portability and Accountability Act (HIPPA) prior to study-specific screening procedures.
* A histologically or cytologically confirmed colorectal cancer that is metastatic, unresectable, or recurrent.
* Patients must have received at least 2 regimens containing 5-Fluorouracil,oxaliplatin, or irinotecan.
* Patients to be enrolled in the Cetuximab or Panitumumab combination arms must have colorectal cancer which is K-Ras wild-type.
* ≥ 18 years of age.
* Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
* Karnofsky performance Status ≥ 70%
* Male or female patients of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose.
* Females of childbearing potential must have a negative serum pregnancy test.
* Aspartate transaminase (AST) and alanine transaminase (ALT) ≤1.5 × upper limit of normal(ULN), or ≤ 2.5 × ULN with metastatic liver disease.
* Hemoglobin (Hgb) ≥ 10 g/dl.
* Total bilirubin ≤ 1.5 × ULN.
* Creatinine ≤ 1.5 × ULN or creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
* Absolute neutrophil count ≥ 1.5 x 10\^9/L.
* Platelets ≥ 100 x 10\^9/L.
* Life expectancy ≥ 3 months.

Exclusion Criteria:

* Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within four weeks of first dose with the exception for a single dose radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 14 days before beginning the administration of BBI608.
* Surgery within 4 weeks prior to first dose.
* Any known symptomatic brain metastases requiring steroids. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment, with image documentation required. Patients must have no clinical symptoms from brain metastases and must be either off steroids or on a stable dose of steroids for at least 2 weeks prior to protocol enrollment. Patients with known leptomeningeal metastases are excluded, even if treated.
* Pregnant or breastfeeding
* Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection)
* Unable or unwilling to swallow BBI608 capsules daily.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.

Primary outcomes:
measure: Disease Control Rate
timeFrame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 24 months
measure: Overall Survival
timeFrame: 4 weeks after the patient has been off study treatment, every 3 months thereafter until death, up to 60 months.
measure: Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of the First Study Cycle
timeFrame: Blood samples drawn on day 5 during the first study cycle
measure: Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle
timeFrame: Blood samples drawn on day 21 during the first study cycle
measure: Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of the First Study Cycle
timeFrame: Blood samples drawn on day 21 during the first study cycle
measure: Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of the First Study Cycle
timeFrame: Blood samples drawn on day 5 during the first study cycle
measure: Determination of the Maximum Observed Concentration (Cmax) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle
timeFrame: Blood samples drawn on day 21 during the first study cycle
measure: Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 5 of the First Study Cycle
timeFrame: Blood samples drawn on day 5 during the first study cycle
measure: Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 480mg, Twice Daily, on Day 21 of the First Study Cycle
timeFrame: Blood samples drawn on day 21 during the first study cycle
measure: Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 240mg, Twice Daily, on Day 21 of the First Study Cycle
timeFrame: Blood samples drawn on day 21 during the first study cycle
measure: Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 5 of the First Study Cycle
timeFrame: Blood samples drawn on day 5 during the first study cycle
measure: Area Under the Plasma Concentration vs. Time Curve (AUClast) of Napabucasin When Administered 500mg, Twice Daily, on Day 21 of the First Study Cycle
timeFrame: Blood samples drawn on day 21 during the first study cycle
measure: Pharmacodynamics
timeFrame: During the first 28 days of the study cycle
measure: Number of Patients With Adverse Events and Serious Adverse Events
timeFrame: The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 4 months.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Denver
country: United States
facility: USOR - Rocky Mountain Cancer Center
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Minneapolis
country: United States
facility: USOR - Minnesota Oncology Hematology
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Portland
country: United States
facility: USOR - Northwest Cancer Specialists
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Institute for Translational Oncology Research, Greenville Hospital System
state: South Carolina
city: Dallas
country: United States
facility: USOR - Texas Oncology Dallas
state: Texas
city: The Woodlands
country: United States
facility: US Oncology Research
state: Texas
city: Tyler
country: United States
facility: USOR - Texas Oncology Tyler
state: Texas
city: Fairfax
country: United States
facility: USOR - Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: Institute for Translational Oncology Research, Greenville Hospital System
name: William J. Edenfield, MD
role: PRINCIPAL_INVESTIGATOR
References: