Clinical trial NCT01325441: A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies
Official title: A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Keywords: BBI608, thymic cancer
Lead sponsor: Sumitomo Pharma America, Inc.
Sponsor class: INDUSTRY
First posted: 2011-03-29
Enrollment: 565
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open label, single arm phase 1 dose escalation study and phase 2 study of BBI608 in combination with paclitaxel in patients with advanced malignancies.

Detailed description: This is an open label, multi-center, single arm phase 1 dose escalation study and phase 2 study of BBI608 in combination with paclitaxel in patients with advanced solid tumors for whom weekly paclitaxel is an acceptable option.

Eligibility criteria: Inclusion Criteria:

1. 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
2. A histologically or cytologically confirmed ovarian, breast, non-small cell lung, melanoma, gastric/GEJ/esophageal or other type of advanced cancer that is metastatic, unresectable, or recurrent and for which weekly paclitaxel is an acceptable therapeutic option.
3. Patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer must also meet the following criteria: a. Must be either platinum-resistant or platinum-refractory according to the following definitions:(1)Platinum-resistant: a response to platinum therapy followed by progression within 6 months after completing therapy (2)Platinum-refractory: best response of stable disease or progression during platinum therapy; b. Must have had prior systemic treatment with a taxane; c. Must have received no more than 4 prior systemic cytotoxic regimens
4. Patients with melanoma must also meet the following criteria: a. If melanoma is BRAF wild-type or has BRAF mutations that are not amenable to BRAF inhibitor therapy, and the patient is a candidate for immunotherapy, must have received ipilimumab; b. If melanoma is positive for the V600E or V600K BRAF mutation, must have received at least one line of prior therapy with a BRAF-specific inhibitor; either alone or in combination.
5. Patients with triple negative breast cancer (estrogen receptor-negative (ER-), progesterone receptor-negative (PR-), and human epidermal growth factor receptor 2-negative (Her2-) must also meet the following criteria: a. Must have received at least one prior chemotherapy regimen for locally advanced or metastatic disease; b. Must have received prior taxane therapy.
6. Patients with NSCLC (adenocarcinoma, squamous, or adenosquamous histopathology) must also meet the following criteria: a. Must have disease that is stage IIIB, not curable by surgery or radiotherapy, or stage IV; b. Must have received at least one prior chemotherapy regimen for locally advanced or metastatic disease; c. EGFR-positive or ALK-positive patients must have received at least one line of EGFR-directed or ALK-directed therapy, respectively; d. Must have received prior taxane therapy.
7. Patients with adenocarcinoma arising from the esophagus, gastroesophageal junction, or stomach must also meet the following criteria: a. Must have received prior treatment with a platinum/fluoropyrimidine-based therapy with or without an anthracycline in the metastatic setting; or, in the adjuvant setting if recurrence occurred within 6 months of completing systemic adjuvant treatment; b. Patients with HER2 positive tumors must have had prior treatment with a Her2 inhibitor (e.g. trastuzumab or lapatinib); c. Patients who have received prior taxane therapy may be enrolled.
8. Patients with thymic carcinoma must have received at least one prior systemic chemotherapy regiment for metastatic, recurrent, locally advanced or otherwise unresectable disease.
9. ≥ 18 years of age
10. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1, see Section 9)
11. Karnofsky performance Status ≥ 70% (Section 15)
12. 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
13. Females of childbearing potential must have a negative serum pregnancy test
14. Aspartate transaminase (AST) and alanine transaminase (ALT) £1.5 × upper limit of normal (ULN), or ≤ 2.5 × ULN with metastatic liver disease
15. Hemoglobin (Hgb) ≥ 10 g/dl
16. Total bilirubin £ 1.5 × ULN
17. Creatinine £ 1.5 ´ ULN or creatinine clearance \> 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
18. Absolute neutrophil count ³ 1.5 x 109/L
19. Platelets ≥ 100 x 109/L
20. Life expectancy ≥ 3 months

Exclusion Criteria:

1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 7 days of first dose provided all treatment-related adverse events have resolved or have been deemed irreversible, with the exception for a single dose radiation up to 8 Gray (equal to 800 RAD) with palliative intent for pain control up to 7 days before beginning the administration of BBI608.
2. Surgery within 4 weeks prior to first dose
3. 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
4. Pregnant or breastfeeding
5. Significant gastrointestinal disorder(s), in the opinion of the Principal Investigator, (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection)
6. Unable or unwilling to swallow BBI608 capsules daily
7. 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
8. Known severe hypersensitivity to paclitaxel
9. Abnormal ECGs (ie, QT prolongation - QTc \> 480 msec, signs of cardiac enlargement or hypertrophy, bundle branch block, signs of ischemia or necrosis and Wolff Parkinson White patterns)

Primary outcomes:
measure: Number of Participants 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.
measure: Determination of the Recommended Phase 2 Dose by Assessing Dose-limiting Toxicities (DLTs)
timeFrame: 28 days
Secondary outcomes:
measure: Determination of the Maximum Observed Concentration (Cmax) and Area Under the Plasma Concentration vs. Time Curve (AUClast)
timeFrame: Blood samples drawn on days 16 and 17 of the first study cycle
measure: Preliminary Anti-tumor Activity of BBI608 When Administered in Combination With Paclitaxel in Patients With Advanced Malignancies
timeFrame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, for an anticipated average of six months
measure: The Objective Response Rate of Napabucasin Administered in Combination With Paclitaxel in Patients With Advanced Malignancies
timeFrame: From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 60 months
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 60 months.
measure: Progression Free Survival of Patients With Advanced Malignancies
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 60 months
measure: Overall Survival of Patients With Advanced Malignancies
timeFrame: 4 weeks after the patient has been off study treatment, every 3 months up to 18 months, then every 6 months thereafter until death, up to 118 months
measure: Pharmacodynamics
timeFrame: Day 17 of cycle 1
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC - University of Southern California Norris Comprehensive Cancer Center
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health (formerly Institute for Translational Oncology Research)
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Cancer Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology- Baylor Charles A. Sammons Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology- Fort Worth
state: Texas
city: Tyler
country: United States
facility: Texas Oncology- Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, P.C.
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Vancouver
country: United States
facility: Compass Oncology- Northwest Cancer Specialists
state: Washington
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Center-Glenn Site
state: Quebec
Study officials:
affiliation: Sumitomo Pharma America, Inc.
name: Claudia Lebedinsky, MD
role: STUDY_DIRECTOR
References: