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A Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Boston Biomedical, Inc
Sponsor:
Information provided by (Responsible Party):
Boston Biomedical, Inc
ClinicalTrials.gov Identifier:
NCT02231723
First received: August 30, 2014
Last updated: September 12, 2016
Last verified: September 2016
  Purpose
This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered in combination with Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin.

Condition Intervention Phase
Metastatic Pancreatic Adenocarcinoma
Drug: BBI608
Drug: Nab-paclitaxel
Drug: Gemcitabine
Drug: Oxaliplatin
Drug: Leucovorin
Drug: Irinotecan
Drug: Fluorouracil
Drug: MM-398
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Metastatic Pancreatic Adenocarcinoma

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: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing tumor assessments every 8 weeks [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing serum CA 19-9 level measurement [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies in adult patients with metastatic pancreatic adenocarcinoma by performing serum carbohydrate antigen 19-9 (CA 19-9) level measurement every 4 weeks

  • Assess pharmacokinetic profile of BBI608 when administered in combination with standard chemotherapies [ Time Frame: On Day 1 and Day 15 of the first cycle prior to dosing and 1, 2, 3, 3.5, 4, 5, 5.5, 7, 8, 9, 10, 11 and 24 hours after first dose ] [ Designated as safety issue: No ]
    Blood sampling to assess the pharmacokinetic profile (Area under the curve) of BBI608.

  • Assess pharmacodynamic activity of BBI608 when administered in combination with standard chemotherapies [ Time Frame: During the first 28 days of treatment ] [ Designated as safety issue: No ]
    Tumor Biopsy to provide information of the biomarkers by histopathology and Cancer Stem Cell assays.


Estimated Enrollment: 250
Study Start Date: August 2014
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: BBI608 in combination with Gemcitabine and nab-Paclitaxel Drug: BBI608
Administered continuously twice daily with doses separated by 12 hours
Other Names:
  • Napabucasin
  • BB608
  • BBI-608
Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle
Other Name: Abraxane, nanoparticle albumin-bound paclitaxel, paclitaxel, ABI-007
Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle
Other Name: Gemzar
Experimental: B: BBI608 in combination with modified FOLFIRINOX Drug: BBI608
Administered continuously twice daily with doses separated by 12 hours
Other Names:
  • Napabucasin
  • BB608
  • BBI-608
Drug: Oxaliplatin
Oxaliplatin 85 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Name: Eloxatin
Drug: Irinotecan
Arm B: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Name: Camptosar
Drug: Fluorouracil
Arm B, D: Fluorouracil 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Fluorouracil 400 mg/m^2 I.V. bolus followed by 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Names:
  • 5-FU
  • Carac
  • Efudex
  • Fluoroplex
  • Adrucil
Experimental: C: BBI608 in combination with FOLFIRI Drug: BBI608
Administered continuously twice daily with doses separated by 12 hours
Other Names:
  • Napabucasin
  • BB608
  • BBI-608
Drug: Leucovorin
Arm C, D: Leucovorin 400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Name: Folinic Acid
Drug: Irinotecan
Arm B: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Irinotecan 165 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Name: Camptosar
Drug: Fluorouracil
Arm B, D: Fluorouracil 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Fluorouracil 400 mg/m^2 I.V. bolus followed by 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Names:
  • 5-FU
  • Carac
  • Efudex
  • Fluoroplex
  • Adrucil
Experimental: D: BBI608 in combination with MM-398, 5-FU and leucovorin Drug: BBI608
Administered continuously twice daily with doses separated by 12 hours
Other Names:
  • Napabucasin
  • BB608
  • BBI-608
Drug: Leucovorin
Arm C, D: Leucovorin 400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Name: Folinic Acid
Drug: Fluorouracil
Arm B, D: Fluorouracil 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle, Arm C: Fluorouracil 400 mg/m^2 I.V. bolus followed by 2400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Names:
  • 5-FU
  • Carac
  • Efudex
  • Fluoroplex
  • Adrucil
Drug: MM-398
MM-398 70 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle
Other Name: Onivyde

Detailed Description:
This is an open label, multi-center, multi-arm, dose-escalation study of BBI608 administered in combination with either Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin. A study cycle will consist of daily and continuous oral administration of BBI608 for four weeks (28 days) in combination with Gemcitabine and nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin. Combination treatment will continue in 28 day cycles until disease progression, unacceptable toxicity or another discontinuation criterion is met. BBI608 may be continued post-progression if the patient is obtaining potential clinical benefit, in the opinion of the investigator. If administration of Gemcitabine and/or nab-Paclitaxel, mFOLFIRINOX, FOLFIRI, or MM-398 with 5-FU and leucovorin is discontinued due to chemotherapy backbone-related toxicities, the administration of BBI608 can be continued.
  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 Harmonisation (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 (HIPAA) prior to study-specific screening procedures.
  2. Patients must have histologic or cytologic evidence of adenocarcinoma of the pancreas, such as a core tissue biopsy or a surgical resection specimen.
  3. Patients must have metastatic disease. Baseline imaging of chest, abdomen and pelvis (CT or MRI) within 21 days prior to initiation of protocol therapy is required.

    1. Patients must have measurable disease as defined by RECIST 1.1.
    2. Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.
  4. Patients enrolling onto Arm A (Gemcitabine and nab-Paclitaxel) or Arm B (mFOLFIRINOX) are allowed to have up to two prior lines of systemic therapy, with adjuvant therapy counted as one line of therapy as long as disease recurrence occurred > 6 months of last dose of therapy. Prior systemic therapy in the metastatic setting is allowed for as long as the therapy contained BBI608 in combination with either Gemcitabine and nab-Paclitaxel or mFOLFIRINOX. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible.

    1. Patients who received Gemcitabine-based therapy in an adjuvant setting will be allowed to be enrolled on Arm A of the trial (Gemcitabine with nab-Paclitaxel) as long as their last Gemcitabine administration was at least 6 months prior to the first dose of BBI608.
    2. Patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel) are allowed to have prior mFOLFIRINOX in combination with BBI608 in the metastatic setting.
    3. Patients enrolling onto Arm B (mFOLFIRINOX) are allowed to have prior Gemcitabine with nab-Paclitaxel in combination with BBI608 in the metastatic setting.
    4. Prior treatment with radiotherapy is allowed.
  5. Patients enrolling onto Arm C (FOLFIRI) or Arm D (MM-398 with 5-FU and leucovorin) must have failed one prior line of gemcitabine-based therapy with or without BBI608 in the metastatic setting. No additional lines of therapy in the metastatic setting are allowed. Prior adjuvant therapy with gemcitabine is allowed as long as disease recurrence occurred > 6 months of last dose of therapy. Toxicities related to prior therapy must have completely resolved (except for alopecia and anemia), or be deemed irreversible. Prior treatment with radiotherapy is allowed.
  6. ≥ 18 years of age.
  7. Patients must have an ECOG Performance Status ≤ 1.
  8. Male or female patients of child-producing potential agree to use contraception or avoidance of pregnancy measures during the study and for 30 days after the last BBI608 dose.
  9. Females of childbearing potential have a negative serum pregnancy test (preceding 72 hours of first day of BBI608 treatment).
  10. Patients with biliary or gastro-duodenal obstruction must have drainage or surgical bypass prior to starting chemotherapy.
  11. Significant or symptomatic amount of ascites should be drained prior to first dose of BBI608.
  12. Patients on Warfarin/Dabigatran/Rivaroxaban anticoagulation may be enrolled for as long as they undergo weekly INR checks for the first 2 months of therapy.

    a. Patients who switch to low molecular weight heparin may be enrolled and weekly INR labs are not mandated for these patients.

  13. Aspartate transaminase (AST) level ≤ 2.5 x upper limit of normal (ULN) and alanine transaminase (ALT) ≤ 2.5 × upper limit of normal (ULN). For patients with liver metastases, AST ≤ 5 ULN, and AST ≤ 5 ULN may be enrolled if agreed upon by the investigator and medical monitor for the sponsor.
  14. Patients must have a total bilirubin level ≤ 1.5 x ULN (≤ 2 x ULN if it is non-rising for a period of 10 days prior to initiation of therapy).
  15. Creatinine level < 1.0 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above or below the institutional normal (as determined by Cockcroft-Gault equation). For patients with a Body Mass Index (BMI) > 30 kg/m^2, lean body weight should be used to calculate the GFR.
  16. Hemoglobin (Hgb) ≥ 9 g/dl
  17. Absolute neutrophil count ≥ 1.5 x 10^9/L
  18. Platelets ≥ 100 x 10^9/L
  19. Acceptable coagulation studies as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (+/-15%).
  20. Patient has no clinically significant abnormalities on urinalysis results.
  21. Life expectancy estimated at ≥ 3 months.

Exclusion Criteria:

  1. Anti-cancer chemotherapy, radiotherapy, immunotherapy, or investigational agents within 14 days of the first dose of BBI608, except for BBI608 for which a washout period is not required.

    1. Patients may begin BBI608 on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days since last receiving anti-cancer treatment which did not include BBI608, provided that all treatment-related adverse events have resolved or have been deemed irreversible (except for alopecia).
    2. Patients who previously received BBI608 for treatment of PDAC on the BBI608-118 (BBI608-201PANC) study may continue with BBI608 in monotherapy between discontinuation of the first chemotherapy backbone and start of the second chemotherapy backbone. Patients may begin chemotherapy backbone on a date determined by the investigator and medical monitor for the sponsor after a minimum of 14 days and a maximum of 30 days since last receiving anti-cancer treatment which included BBI608, provided that all treatment-related adverse events have resolved or have been deemed irreversible (except for alopecia).
  2. Patients with neuroendocrine neoplasms will be excluded.
  3. Major surgery, other than diagnostic surgery (e.g., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to first dose.
  4. Any brain metastases including leptomeningeal metastases, are excluded, even if treated and stable.
  5. History of posterior reversible encephalopathy syndrome.
  6. Neurosensory neuropathy ≥ grade 2 at baseline.
  7. Pregnant or breastfeeding.
  8. Significant gastrointestinal disorder(s) that would, in the opinion of the Principal Investigator, prevent absorption of an orally available agent (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection and small intestinal resection).
  9. Unable or unwilling to swallow BBI608 capsules daily.
  10. Uncontrolled chronic diarrhea ≥ grade 2 at baseline.
  11. Uncontrolled intercurrent illness including, but not limited to uncontrolled active infection (including bacterial, viral or fungal requiring systemic therapy), clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled 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.
  12. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
  13. History of other active malignancies.
  14. Enrollment on any additional investigational agent study. Enrollment on concurrent observational study is allowed following consultation with the Sponsor.
  15. Patients planning to take a vacation for 7 or more consecutive days during the course of the study.
  16. For patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel)

    a. Known hypersensitivity to Gemcitabine or taxanes. i. Patients with history of Gemcitabine toxicity in the adjuvant setting requiring more than 1 dose level reduction are excluded.

    b. Significant cardiac disease, including the following: unstable angina, New York Heart Association class III-IV congestive heart failure, myocardial infarction within six months prior to study enrollment.

    c. History of hemolytic-uremic syndrome. d. History of posterior reversible encephalopathy syndrome. e. Known infection with Human Immunodeficiency Virus (HIV), and/or active infection with hepatitis B, or hepatitis C.

    f. History of active Peripheral Artery Disease (treated peripheral artery disease that is stable for at least 6 months is allowed).

  17. For patients enrolling onto Arm B (mFOLFIRINOX) or Arm C (FOLFIRI)

    1. Known hypersensitivity to 5-fluorouracil/leucovorin
    2. Known dihydropyrimidine dehydrogenase (DPD) deficiency
    3. Known hypersensitivity to oxaliplatin or other platinum containing compounds
    4. Known hypersensitivity to irinotecan
    5. Uncontrolled seizure disorder, active neurological disease, or known CNS disease.
    6. Known Gilbert's syndrome
    7. Significant cardiac disease, including the following: unstable angina, New York Heart Association class II-IV congestive heart failure, myocardial infarction within six months prior to study enrollment.
  18. For patients enrolling onto Arm D (MM-398 with 5-FU and leucovorin)

    1. Prior irinotecan treatment
    2. Arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) < 6 months prior to enrollment
    3. Known hypersensitivity to any of the components of MM-398, other liposomal products, fluoropyrimidines or leucovorin
    4. Known dihydropyrimidine dehydrogenase (DPD) deficiency
  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: NCT02231723

Contacts
Contact: Boston Biomedical 617-674-6800

Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
United States, Indiana
Parkview Research Center Recruiting
Fort Wayne, Indiana, United States, 46845
Indiana University Health Goshen Center for Cancer Care Recruiting
Goshen, Indiana, United States, 46526
Contact: Vanessa DePue    574-364-2888    vdepue@goshenhealth.com   
Indiana University Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Janet Flynn, RN    317-274-0972    janflynn@iupui.edu   
Indiana University Health Arnett Hospital Recruiting
Lafayette, Indiana, United States, 47905
Indiana University Health Ball Memorial Hospital Recruiting
Muncie, Indiana, United States, 47303
Contact: Angie Patterson, RN    765-751-5849    apatterson2@iuhealth.org   
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Henderson, Nevada, United States, 89014
Contact: Crystal Speaks    281-863-4697    Crystal.Speaks@mckesson.com   
United States, Ohio
The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Hamida Umar    614-685-6406    Hamida.umar@osumc.edu   
United States, Tennessee
The University of Tennessee Medical Center Recruiting
Knoxville, Tennessee, United States, 37920
United States, Texas
Texas Oncology - Austin Midtown Recruiting
Austin, Texas, United States, 78705
Contact: Crystal Speaks    281-863-4697    Crystal.Speaks@mckesson.com   
Texas Oncology - Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Crystal Speaks    281-863-4697    Crystal.Speaks@mckesson.com   
Texas Oncology - SAT&BC Recruiting
San Antonio, Texas, United States, 78216
Contact: Crystal Speaks    281-863-4697    Crystal.Speaks@mckesson.com   
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Contact: Crystal Speaks    281-863-4697    Crystal.Speaks@mckesson.com   
United States, Washington
Yakima Valley Memorial Hospital / North Star Lodge Withdrawn
Yakima, Washington, United States, 98902
Sponsors and Collaborators
Boston Biomedical, Inc
  More Information

Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT02231723     History of Changes
Other Study ID Numbers: BBI608-118  BBI608-201PANC 
Study First Received: August 30, 2014
Last Updated: September 12, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Boston Biomedical, Inc:
Digestive System Neoplasms
Endocrine Gland Neoplasms
Pancreatic neoplasms
Pancreatic cancer, adult
Pancreatic cancer
Pancreas cancer
Pancreatic diseases
Adenoma, Islet Cell
Carcinoma, Islet Cell
Carcinoma, Pancreatic Ductal
Gemcitabine
Gemzar
Nab-paclitaxel
Paclitaxel
Abraxane
Oxaliplatin
Leucovorin
Irinotecan
Fluorouracil
5-FU
MM-398

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Irinotecan
Gemcitabine
Oxaliplatin
Albumin-Bound Paclitaxel
Fluorouracil
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on September 27, 2016