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

Sponsor
Sumitomo Pharma Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01325441
Collaborator
(none)
565
Enrollment
22
Locations
1
Arm
122
Duration (Months)
25.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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
Phase 1/Phase 2

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 Design

Study Type:
Interventional
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 :
Apr 1, 2011
Actual Primary Completion Date :
Jun 1, 2021
Actual Study Completion Date :
Jun 1, 2021

Arms and Interventions

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
    Other Names:
  • Abraxane

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Safety by reporting the 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 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.

    2. Determination of the Recommended Phase 2 Dose by assessing dose-limiting toxicities (DLTs) [6 months]

      Determination of the Recommended Phase 2 dose (RP2D) of napabucasin when administered with paclitaxel in patients with advanced malignancies.

    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 [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.

    2. Pharmacokinetic profile of BBI608 and paclitaxel assessed by area under the plasma concentration versus time curve [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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)

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • Sumitomo Pharma Oncology, Inc.

    Investigators

    • Study Director: Claudia Lebedinsky, MD, Sumitomo Pharma Oncology, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sumitomo Pharma Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT01325441
    Other Study ID Numbers:
    • BBI608-201
    First Posted:
    Mar 29, 2011
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Keywords provided by Sumitomo Pharma Oncology, Inc.
    BBI608, thymic cancer
    Additional relevant MeSH terms:
    Neoplasms
    Paclitaxel

    Study Results

    No Results Posted as of Apr 5, 2022