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

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ClinicalTrials.gov Identifier: NCT01325441
Recruitment Status : Completed
First Posted : March 29, 2011
Last Update Posted : July 14, 2021
Sponsor:
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

Tracking Information
First Submitted Date  ICMJE March 25, 2011
First Posted Date  ICMJE March 29, 2011
Last Update Posted Date July 14, 2021
Study Start Date  ICMJE April 2011
Actual Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
  • Safety by reporting the adverse events and serious adverse events [ Time Frame: The time from the date of first treatment, while the patient is taking napabucasin, and for 30 days after stopping therapy, an average of 6 months ]
    Assessment of safety of napabucasin given in combination with paclitaxel in patients with advanced malignancies by reporting of adverse events and serious adverse events.
  • Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 months ]
    Determination of the Recommended Phase 2 dose (RP2D) of napabucasin when administered with paclitaxel in patients with advanced malignancies.
Original Primary Outcome Measures  ICMJE
 (submitted: March 28, 2011)
  • Safety by reporting the adverse events and serious adverse events [ Time Frame: 6 months ]
  • Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2021)
  • Preliminary anti-tumor activity of BBI608 when administered in combination with paclitaxel in patients with advanced malignancies by performing tumor assessments every 8 weeks [ Time Frame: Anti-tumor activity is assessed every 8 weeks, from the first dose of BBI608 to 30 days after the last dose of BBI608, an expected average of 6 months ]
    To assess the preliminary anti-tumor activity of napabucasin administered in combination with paclitaxel.
  • Pharmacokinetic profile of BBI608 and paclitaxel assessed by area under the plasma concentration versus time curve [ Time Frame: On Day 3 and Day 17 of the first cycle prior to dosing and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 8.5, 9, 10, 11, 24 and 27 hours after first dose ]
    Blood sampling to assess the pharmacokinetic profile of BBI608 administered in combination with paclitaxel.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2011)
  • To assess the preliminary anti-tumor activity of BBI608 when administered in combination with paclitaxel in patients with advanced malignancies by performing tumor assessments every 8 weeks [ Time Frame: 6 months ]
  • Observe area under the plasma concentration versus time curve of BBI608 and paclitaxel [ Time Frame: On Day 3 and Day 17 of the first cycle prior to dosing and 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 8.5, 9, 10, 11, 24 and 27 hours after first dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies
Official Title  ICMJE A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE
  • Drug: BBI608
    Other Names:
    • Napabucasin
    • BB608
    • BBI-608
  • Drug: Paclitaxel
    Other Name: Abraxane
Study Arms  ICMJE Experimental: BBI608 and Paclitaxel
Patients will receive BBI608 orally continuously at dose levels specified for their respective dose cohorts. 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.
Interventions:
  • Drug: BBI608
  • Drug: Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 21, 2020)
565
Original Estimated Enrollment  ICMJE
 (submitted: March 28, 2011)
50
Actual Study Completion Date  ICMJE June 1, 2021
Actual Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01325441
Other Study ID Numbers  ICMJE BBI608-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sumitomo Dainippon Pharma Oncology, Inc
Study Sponsor  ICMJE Sumitomo Dainippon Pharma Oncology, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Claudia Lebedinsky, MD Sumitomo Dainippon Pharma Oncology, Inc
PRS Account Sumitomo Dainippon Pharma Oncology, Inc
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP