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Trial record 4 of 15 for:    Kansas HCC sorafenib

A Study of BBI608 in Combination With Sorafenib, or BBI503 in Combination With Sorafenib in Adult Patients With Hepatocellular Carcinoma

This study is currently recruiting participants.
Verified August 2017 by Boston Biomedical, Inc
Sponsor:
ClinicalTrials.gov Identifier:
NCT02279719
First Posted: October 31, 2014
Last Update Posted: August 22, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Boston Biomedical, Inc
  Purpose
This is an open label, three-arm, phase 1 dose escalation study and phase 2 study of BBI608 in combination with sorafenib, or BBI503 in combination with sorafenib. The study population is adult patients with advanced hepatocellular carcinoma who have not received systemic chemotherapy.

Condition Intervention Phase
Hepatocellular Carcinoma Drug: BBI608 Drug: BBI503 Drug: Sorafenib Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib/II Clinical Study of BBI608 in Combination With Sorafenib, or BBI503 in Combination With Sorafenib in Adult Patients With Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Boston Biomedical, Inc:

Primary Outcome Measures:
  • Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) (Phase 1 portion) [ Time Frame: 6 weeks including 2-week Sorafenib run-in period prior to initiation of combination therapy ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Adverse events will be assessed at baseline, while the participant is taking drugs, and for 30 days after stopping therapy. The average length of this duration is expected to be approximately 7 months. ]
    Assessment of safety of either BBI608 or BBI503 given in combination with sorafenib to patients with hepatocellular carcinoma by reporting of adverse events and serious adverse events

  • Assessment of the preliminary anti-tumor activity by performing tumor assessments every 8 weeks (Phase 2 portion) [ Time Frame: 6 months ]
    The radiologic assessments will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST for patients with hepatocellular carcinoma.


Secondary Outcome Measures:
  • Pharmacokinetic profile of BBI608 or BBI503 when administered in combination with sorafenib as assessed by maximum plasma concentration and area under the curve [ Time Frame: On Day 15 and Day 16 of the first cycle and Day 15 of the second cycle, prior to dosing and every one hours to 11 hours and 24 hours after first dose ]
    Blood sampling to assess the pharmacokinetic profile (maximum plasma concentration and area under the curve) of either BBI608 or BBI503.

  • Pharmacodynamic activity of BBI608 or BBI503 when administered in combination with sorafenib as assessed by tumor biopsy and Cancer Stem Cell assays as well as the concentration of study drug in tumors [ Time Frame: On Day 15 of the 2nd cycle ]
    Tumor Biopsy to provide information of the biomarkers by histopathology and Cancer Stem Cell assays as well as the concentration of study drug in tumors.


Estimated Enrollment: 114
Study Start Date: December 2014
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BBI608 and Sorafenib Drug: BBI608
BBI608 will be administered in combination with sorafenib at the RP2D determined during the phase 1 dose-escalation portion of study.
Other Names:
  • Napabucasin
  • BBI-608
  • BB608
Drug: Sorafenib
Sorafenib will be administered at a fixed dose of 400 mg twice daily (800 mg total daily dose). Sorafenib should be taken on an empty stomach, one hour prior to or two hours after meals. Sorafenib should not be taken with study drug, and at least 2 hours should separate a dose of sorafenib from a dose of study drug.
Other Name: Nexavar
Experimental: BBI503 and Sorafenib Drug: BBI503
BBI503 will be administered in combination with sorafenib at the RP2D determined during the phase 1 dose-escalation portion of study.
Other Names:
  • Amcasertib
  • BBI-503
  • BB503
Drug: Sorafenib
Sorafenib will be administered at a fixed dose of 400 mg twice daily (800 mg total daily dose). Sorafenib should be taken on an empty stomach, one hour prior to or two hours after meals. Sorafenib should not be taken with study drug, and at least 2 hours should separate a dose of sorafenib from a dose of study drug.
Other Name: Nexavar
Active Comparator: Sorafenib Drug: Sorafenib
Sorafenib will be administered at a fixed dose of 400 mg twice daily (800 mg total daily dose). Sorafenib should be taken on an empty stomach, one hour prior to or two hours after meals. Sorafenib should not be taken with study drug, and at least 2 hours should separate a dose of sorafenib from a dose of study drug.
Other Name: Nexavar

Detailed Description:

This is an open label, three-arm, phase 1 dose escalation study and phase 2 study of BBI608 in combination with sorafenib, or BBI503 in combination with sorafenib. The study population is adult patients with advanced hepatocellular carcinoma (HCC) who have not received systemic chemotherapy.

The phase 1 portion will involve dose-escalation of BBI608 administered in combination with a fixed starting dose of sorafenib (Arm 1), and dose escalation of BBI503 administered in combination with a fixed starting dose of sorafenib (Arm 2). The fixed starting dose-level of sorafenib for both arms will be 400 mg twice daily (800 mg total daily dose). Eligible patients will be randomized to either Arm 1 or Arm 2.

The phase 2 portion will be an open-label, 3-arm, randomized trial of patients with advanced HCC who have not received prior systemic treatment. Patients will be randomized to receive either, Arm 1: sorafenib administered in combination with BBI608 (at the RP2D determined for BBI608 plus sorafenib during the phase 1 portion); Arm 2: sorafenib in combination with BBI503 (at the RP2D determined for BBI503 plus sorafenib during the phase 1 portion), or Arm 3: sorafenib alone at a starting dose of 400 mg twice daily. The starting dose for sorafenib is the same for all study arms.

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria

  1. Signed written informed consent must be obtained and documented according to International Conference on Harmonisation (ICH) and local regulatory requirements
  2. Histologically or cytologically confirmed hepatocellular carcinoma that is metastatic, unresectable, or recurrent.

    1. Patients must not be candidates for curative resection
    2. Patients who have recurrent disease after having had one or more prior resections may be eligible, provided that they are not candidates for further curative resection.
    3. Patients who have recurrent hepatocellular carcinoma following hepatic transplantation are excluded unless the following criteria are met:

    i. Transplantation was performed at least 6 months prior to the relapse of HCC. ii. Patients are on stable immune suppressive therapy with no clinical evidence of rejection.

    iii. Are receiving ≤ 2.5 mg everolimus daily. d. Patients with known HIV infection are excluded. e. Patients with Hepatitis B are eligible provided there is no active viral replication. Patients with Hepatitis C who are not on interferon are eligible.

  3. Patients who have a diagnosis of hepatocellular carcinoma made through radiologic imaging may be eligible, provided they meet the criteria according to the American Association for the Study of Liver Disease, AASLD (Bruix and Sherman, 2005; Bruix and Sherman, 2011)
  4. Patients must be candidates for sorafenib
  5. Must have had no previous systemic anti-cancer treatment, though previous loco-regional therapy is allowed:

    a. Prior treatment with any of the following is allowed: trans-arterial embolization, trans-arterial chemo-embolization, percutaneous ethanol injection, radio-embolization, radio-frequency ablation, or other ablation techniques.

  6. Must be Child-Pugh class A

    a. Patients with uncontrolled massive ascites or presence of hepatic encephalopathy are excluded

  7. Must have total serum bilirubin ≤ 3 mg/dl
  8. ≥ 18 years of age
  9. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  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 or BBI503 dose
  12. Females of childbearing potential must have a negative serum pregnancy test
  13. Aspartate Aminotransferase (AST) and Alanine transaminase (ALT) < 5.0x the upper limit of normal (ULN)
  14. Glomerular filtration rate (GFR) > 45 mL/min/1.73m^2 according to the Cockcroft-Gault estimation.

13. Hemoglobin ≥ 8.5 mg/dl 14. Absolute neutrophil count ≥ 1.5 x 10^9/L 15. Platelets ≥ 75 x 10^9/L 16. Life expectancy ≥ 3 months

Exclusion Criteria

  1. Previous treatment with sorafenib
  2. Patients with known hypersensitivity to sorafenib or any other component of sorafenib.
  3. Previous systemic anti-vascular endothelial growth factor (VEGF) or any prior systemic anti-cancer therapy, including prior treatment with systemic agents such as regorafenib, ramucirumab, pazopanib, or experimental agents such as brivanib.
  4. Have had a surgical procedure requiring general anesthesia or inpatient hospitalization for recovery less than 4 weeks prior to beginning protocol therapy.
  5. Have had a loco-regional procedure for the treatment of hepatocellular carcinoma (such as a percutaneous, trans-arterial, or radio-ablative procedure) less than 4 weeks prior to beginning protocol therapy. Protocol therapy may begin a minimum of 4 weeks after such a procedure provided the following criteria are met:

    1. There is progression of disease documented by RECIST 1.1
    2. All adverse events from the procedure have resolved or have been deemed irreversible and the patient meets inclusion criteria.
  6. Any known symptomatic or untreated brain metastases requiring increase of steroid dose within 2 weeks prior to starting on study. Patients with treated brain metastases must be stable for 4 weeks after completion of that treatment. 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.
  7. Pregnant or breastfeeding
  8. Significant gastrointestinal disorder(s), (e.g., Crohn's disease, ulcerative colitis, extensive gastric and small intestine resection) such that, in the opinion of the treating investigator, absorption of oral medications may be impaired.
  9. Unable or unwilling to swallow BBI608, BBI503, or sorafenib capsules or tablets
  10. Uncontrolled inter-current 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), or uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements (e.g. no reliable transportation).
  11. Subjects with a history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present that, in the opinion of the investigator, will not affect patient outcome in the setting of current hepatocellular carcinoma diagnosis.
  12. Abnormal ECGs which are clinically significant such as QT prolongation (QTc > 480 msec), clinically significant cardiac enlargement or hypertrophy, new bundle branch block, or signs of active ischemia. Patients with evidence of prior infarction who are New York Heart Association (NYHA) functional classes II, III, or IV are excluded, as are patients with marked arrhythmias such as Wolff Parkinson White pattern or complete atrioventricular (AV) dissociation.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02279719


Contacts
Contact: Boston Biomedical 617-674-6800

  Show 33 Study Locations
Sponsors and Collaborators
Boston Biomedical, Inc
  More Information

Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT02279719     History of Changes
Other Study ID Numbers: BBIHCC-103
BBI608-503-103HCC ( Other Identifier: Boston Biomedical, Inc. )
First Submitted: October 24, 2014
First Posted: October 31, 2014
Last Update Posted: August 22, 2017
Last Verified: August 2017

Additional relevant MeSH terms:
Sorafenib
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs