Clinical Trial - NCT01325441

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


Sponsor: Sumitomo Dainippon Pharma Oncology, Inc


Information provided by (Responsible party): Sponsor Identifier: NCT01325441

Protocol Info

Short Description: Phase IB/II of BBI608 and Paclitaxel in Advanced Malignancies
Long Description: A Phase Ib/II Clinical Study of BBI608 Administered with Paclitaxel in Adult Patients with Advanced Malignancies
MGH Status: Closed
Sponsor: Boston Biomedical, Inc.
Disease Program: Phase I

Next Steps

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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. Currently the study is only enrolling patients with thymic carcinoma.
Condition Title Intervention Phase
Cancer BBI608 Paclitaxel Phase 1/Phase 2
Study Type Interventional
Official Title A Phase Ib/II Clinical Study of BBI608 Administered With Paclitaxel in Adult Patients With Advanced Malignancies

Primary Outcome Measures

Safety by reporting the adverse events and serious adverse events [Time Frame: 6 months] [Designated as safety issue: ]

Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs) [Time Frame: 6 months] [Designated as safety issue: ]

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: ]

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: ]

Estimated Enrollment: 570
Study Start Date: April 2011
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: December 2020
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.


Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly 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)

Contacts and Locations

Please refer to this study by its identifier: NCT01325441


  • United States, California
    • USC - University of Southern California Norris Comprehensive Cancer Center Los Angeles, California, United States, 90033
  • United States, Colorado
    • Rocky Mountain Cancer Centers Denver, Colorado, United States, 80218
  • United States, Indiana
    • Indiana University Simon Cancer Center Indianapolis, Indiana, United States, 46202
  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02114
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
  • United States, Nevada
    • Comprehensive Cancer Centers of Nevada Las Vegas, Nevada, United States, 89169
  • United States, New York
    • New York Oncology Hematology, P.C. Albany, New York, United States, 12206
  • United States, Ohio
    • Ohio State University Wexner Medical Center Columbus, Ohio, United States, 43210
  • United States, Pennsylvania
    • Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104
  • United States, South Carolina
    • Prisma Health (formerly Institute for Translational Oncology Research) Greenville, South Carolina, United States, 29605
  • United States, Tennessee
    • University of Tennessee Medical Center Cancer Institute Knoxville, Tennessee, United States, 37920
  • United States, Texas
    • Texas Oncology- Baylor Charles A. Sammons Cancer Center Dallas, Texas, United States, 75246
    • Texas Oncology- Fort Worth Fort Worth, Texas, United States, 76104
    • Texas Oncology- Tyler Tyler, Texas, United States, 75702
  • United States, Virginia
    • Virginia Cancer Specialists, P.C. Fairfax, Virginia, United States, 22031
    • Virginia Oncology Associates Norfolk, Virginia, United States, 23502
  • United States, Washington
    • Compass Oncology- Northwest Cancer Specialists Vancouver, Washington, United States, 98684
  • Canada, British Columbia
    • British Columbia Cancer Agency Vancouver, British Columbia, Canada, V5Z 4E6
  • Canada, Ontario
    • Ottawa Hospital Cancer Centre Ottawa, Ontario, Canada, K1H 8L6
  • Canada, Quebec
    • Jewish General Hospital Montreal, Quebec, Canada, H3T 1E2
    • St. Mary's Hospital Montreal, Quebec, Canada, H3T 1M5
    • McGill University Health Center-Glenn Site Montreal, Quebec, Canada, H4A 3J1

Sponsors and Collaborators

Sumitomo Dainippon Pharma Oncology, Inc

More Information

No publications provided

Responsible Party: Sponsor Identifier: NCT01325441
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:

BBI608, thymic cancer

Additional relevant MeSH terms:



Next Steps

If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation. processed this data on September 03, 2020