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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Boston Biomedical, Inc
Sponsor:
Information provided by (Responsible Party):
Boston Biomedical, Inc
ClinicalTrials.gov Identifier:
NCT01325441
First received: March 25, 2011
Last updated: July 5, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Cancer
Drug: BBI608
Drug: Paclitaxel
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by Boston Biomedical, Inc:

Primary Outcome Measures:
  • Safety by reporting the adverse events and serious adverse events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 390
Study Start Date: April 2011
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: BBI608
Other Names:
  • Napabucasin
  • BB608
  • BBI-608
Drug: Paclitaxel

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. ≥ 18 years of age
  9. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1, see Section 9)
  10. Karnofsky performance Status ≥ 70% (Section 15)
  11. 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
  12. Females of childbearing potential must have a negative serum pregnancy test
  13. Aspartate transaminase (AST) and alanine transaminase (ALT) £1.5 × upper limit of normal (ULN), or ≤ 2.5 × ULN with metastatic liver disease
  14. Hemoglobin (Hgb) ≥ 10 g/dl
  15. Total bilirubin £ 1.5 × ULN
  16. Creatinine £ 1.5 ´ ULN or creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  17. Absolute neutrophil count ³ 1.5 x 109/L
  18. Platelets ≥ 100 x 109/L
  19. 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01325441

Contacts
Contact: Boston Biomedical 617-674-6800

  Show 21 Study Locations
Sponsors and Collaborators
Boston Biomedical, Inc
  More Information

Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT01325441     History of Changes
Other Study ID Numbers: BBI608-201 
Study First Received: March 25, 2011
Last Updated: July 5, 2016
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by Boston Biomedical, Inc:
BBI608

Additional relevant MeSH terms:
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2016