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

Cancer Clinical Trial

Official title:

A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01325441
• Other study ID #: BBI608-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2011
• Est. completion date: June 1, 2021

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 565
• Est. completion date: June 1, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cancer
• Neoplasms

Intervention

Drug:
• BBI608

• Paclitaxel

Locations

Country	Name	City	State
Canada	Jewish General Hospital	Montreal	Quebec
Canada	McGill University Health Center-Glenn Site	Montreal	Quebec
Canada	St. Mary's Hospital	Montreal	Quebec
Canada	Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Texas Oncology- Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Rocky Mountain Cancer Centers	Denver	Colorado
United States	Virginia Cancer Specialists, P.C.	Fairfax	Virginia
United States	Texas Oncology- Fort Worth	Fort Worth	Texas
United States	Prisma Health (formerly Institute for Translational Oncology Research)	Greenville	South Carolina
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	University of Tennessee Medical Center Cancer Institute	Knoxville	Tennessee
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	USC - University of Southern California Norris Comprehensive Cancer Center	Los Angeles	California
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	Texas Oncology- Tyler	Tyler	Texas
United States	Compass Oncology- Northwest Cancer Specialists	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events and Serious Adverse Events	Assessment of safety of napabucasin administered in participants with advanced malignancies for whom weekly paclitaxel was an acceptable option by reporting of adverse events and serious adverse events	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.
Primary	Determination of the Recommended Phase 2 Dose by Assessing Dose-limiting Toxicities (DLTs)	Determination of the Recommended Phase 2 dose (RP2D) of napabucasin when administered with paclitaxel in patients with advanced malignancies.	28 days
Secondary	Determination of the Maximum Observed Concentration (Cmax) and Area Under the Plasma Concentration vs. Time Curve (AUClast)	To determine the maximum concentration of napabucasin and the area under the plasma concentration vs. time curve of napabucasin when administered in combination with weekly paclitaxel	Blood samples drawn on days 16 and 17 of the first study cycle
Secondary	Preliminary Anti-tumor Activity of BBI608 When Administered in Combination With Paclitaxel in Patients With Advanced Malignancies	To assess the preliminary anti-tumor activity, specifically the objective response rate (ORR) of napabucasin administered in combination with paclitaxel. The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response who have measurable disease at baseline imaging.	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
Secondary	The Objective Response Rate of Napabucasin Administered in Combination With Paclitaxel in Patients With Advanced Malignancies	Assessment of the objective response rate (ORR) of napabucasin administered in combination with paclitaxel in patients with advanced malignancies.; Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; The Objective Response Rate (ORR) is the proportion of participants with a complete response or partial response.	From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 60 months
Secondary	Disease Control Rate	To determine the disease control rate (CDR) of napabucasin administered in combination with paclitaxel in patients with advanced malignancies.; Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. The Disease Control Rate (DCR) is the proportion of patients whose best overall response is CR, PR or SD.	From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 60 months.
Secondary	Progression Free Survival of Patients With Advanced Malignancies	The effect of napabucasin given in combination with paclitaxel on Progression Free Survival (PFS) of patients with advanced malignancies.; Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	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
Secondary	Overall Survival of Patients With Advanced Malignancies	The effect of napabucasin given in combination with paclitaxel on Overall Survival (OS) of patients with advanced malignancies	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
Secondary	Pharmacodynamics	To determine the response (increase or decrease) of biomarkers from biopsied tumors following the administration of napabucasin	Day 17 of cycle 1