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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01325441
Recruitment Status : Active, not recruiting
First Posted : March 29, 2011
Last Update Posted : April 28, 2021
Information provided by (Responsible Party):
Sumitomo Dainippon Pharma Oncology, Inc

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.

Condition or disease Intervention/treatment Phase
Cancer Drug: BBI608 Drug: Paclitaxel Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 565 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies
Study Start Date : April 2011
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Paclitaxel

Arm Intervention/treatment
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

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

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01325441

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Sponsors and Collaborators
Sumitomo Dainippon Pharma Oncology, Inc
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Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc Identifier: NCT01325441    
Other Study ID Numbers: BBI608-201
First Posted: March 29, 2011    Key Record Dates
Last Update Posted: April 28, 2021
Last Verified: April 2021
Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:
BBI608, thymic cancer
Additional relevant MeSH terms:
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Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action