A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies

NCT ID: NCT01325441

Last Updated: 2023-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 565 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2021-06-01

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.

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BBI608 and Paclitaxel 200mg BID

Patients will receive BBI608 orally continuously at 200mg BID. A treatment cycle will be 4 weeks (28 days). BBI608 will be administered twice daily. On days 3, 10, and 17 of each 28 day cycle, patients will receive a 1 hour infusion of paclitaxel. Cycles will be repeated until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, adjustment is permitted.

Group Type: EXPERIMENTAL

BBI608

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

BBI608 and Paclitaxel 240mg BID

Patients will receive BBI608 orally continuously at 240mg BID. A treatment cycle will be 4 weeks (28 days). BBI608 will be administered twice daily. On days 3, 10, and 17 of each 28 day cycle, patients will receive a 1 hour infusion of paclitaxel. Cycles will be repeated until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, adjustment is permitted.

Group Type: EXPERIMENTAL

BBI608

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

BBI608 and Paclitaxel 400mg BID

Patients will receive BBI608 orally continuously at 400mg BID. A treatment cycle will be 4 weeks (28 days). BBI608 will be administered twice daily. On days 3, 10, and 17 of each 28 day cycle, patients will receive a 1 hour infusion of paclitaxel. Cycles will be repeated until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, adjustment is permitted.

Group Type: EXPERIMENTAL

BBI608

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

BBI608 and Paclitaxel 480mg BID

Patients will receive BBI608 orally continuously at 480mg BID. A treatment cycle will be 4 weeks (28 days). BBI608 will be administered twice daily. On days 3, 10, and 17 of each 28 day cycle, patients will receive a 1 hour infusion of paclitaxel. Cycles will be repeated until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, adjustment is permitted.

Group Type: EXPERIMENTAL

BBI608

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

BBI608 and Paclitaxel 500mg BID

Patients will receive BBI608 orally continuously at 500mg BID. A treatment cycle will be 4 weeks (28 days). BBI608 will be administered twice daily. On days 3, 10, and 17 of each 28 day cycle, patients will receive a 1 hour infusion of paclitaxel. Cycles will be repeated until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, adjustment is permitted.

Group Type: EXPERIMENTAL

BBI608

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Interventions

BBI608

Intervention Type: DRUG

Paclitaxel

Intervention Type: DRUG

Other Intervention Names

Napabucasin; BB608; BBI-608; Abraxane

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sumitomo Pharma America, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Claudia Lebedinsky, MD

Role: STUDY_DIRECTOR

Sumitomo Pharma America, Inc.

Locations

USC - University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

New York Oncology Hematology, P.C.

Albany, New York, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Prisma Health (formerly Institute for Translational Oncology Research)

Greenville, South Carolina, United States

University of Tennessee Medical Center Cancer Institute

Knoxville, Tennessee, United States

Texas Oncology- Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Texas Oncology- Fort Worth

Fort Worth, Texas, United States

Texas Oncology- Tyler

Tyler, Texas, United States

Virginia Cancer Specialists, P.C.

Fairfax, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Compass Oncology- Northwest Cancer Specialists

Vancouver, Washington, United States

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

St. Mary's Hospital

Montreal, Quebec, Canada

McGill University Health Center-Glenn Site

Montreal, Quebec, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

BBI608-201

Identifier Type: -

Identifier Source: org_study_id