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Metastatic Pancreatic AdenocarcinomaPhase 1NCT02231723

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

A Phase 1 study testing BBI608, Nab-paclitaxel and Gemcitabine in people with Metastatic Pancreatic Adenocarcinoma, run by Sumitomo Pharma America, Inc. at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Pancreatic Adenocarcinoma
What is being tested?
BBI608, Nab-paclitaxel and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
139 participants
Where
12 sitesUnited States
Study dates
Aug 2014to Jun 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Patients must have histologic or cytologic evidence of adenocarcinoma of the pancreas, such as a core tissue biopsy or a surgical resection specimen.
  • 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.
  • Patients must have measurable disease as defined by RECIST 1.1.
  • Patients with locally advanced unresectable pancreatic ductal adenocarcinoma are excluded.
  • 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.
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  • 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.
  • Patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel) are allowed to have prior mFOLFIRINOX in combination with BBI608 in the metastatic setting.
  • Patients enrolling onto Arm B (mFOLFIRINOX) are allowed to have prior Gemcitabine with nab-Paclitaxel in combination with BBI608 in the metastatic setting.
  • Prior treatment with radiotherapy is allowed.
  • 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.
  • ≥ 18 years of age.
  • Patients must have an ECOG Performance Status ≤ 1.
  • 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.
  • Females of childbearing potential have a negative serum pregnancy test (preceding 72 hours of first day of BBI608 treatment).
  • Patients with biliary or gastro-duodenal obstruction must have drainage or surgical bypass prior to starting chemotherapy.
  • Significant or symptomatic amount of ascites should be drained prior to first dose of BBI608.
  • 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.
  • Patients who switch to low molecular weight heparin may be enrolled and weekly INR labs are not mandated for these patients.
  • 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.
  • 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).
  • 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.
  • Hemoglobin (Hgb) ≥ 9 g/dl
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Acceptable coagulation studies as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (+/-15%).
  • Patient has no clinically significant abnormalities on urinalysis results.
  • Life expectancy estimated at ≥ 3 months.

Who cannot join

  • 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.
  • 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).
  • 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).
  • Patients with neuroendocrine neoplasms will be excluded.
  • 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.
  • Any brain metastases including leptomeningeal metastases, are excluded, even if treated and stable.
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  • History of posterior reversible encephalopathy syndrome.
  • Neurosensory neuropathy ≥ grade 2 at baseline.
  • Pregnant or breastfeeding.
  • 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).
  • Unable or unwilling to swallow BBI608 capsules daily.
  • Uncontrolled chronic diarrhea ≥ grade 2 at baseline.
  • 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.
  • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
  • History of other active malignancies.
  • Enrollment on any additional investigational agent study. Enrollment on concurrent observational study is allowed following consultation with the Sponsor.
  • Patients planning to take a vacation for 7 or more consecutive days during the course of the study.
  • For patients enrolling onto Arm A (Gemcitabine with nab-Paclitaxel)
  • 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.
  • 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.
  • 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.
  • History of active Peripheral Artery Disease (treated peripheral artery disease that is stable for at least 6 months is allowed).
  • For patients enrolling onto Arm B (mFOLFIRINOX) or Arm C (FOLFIRI)
  • Known hypersensitivity to 5-fluorouracil/leucovorin
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Known hypersensitivity to oxaliplatin or other platinum containing compounds
  • Known hypersensitivity to irinotecan
  • Uncontrolled seizure disorder, active neurological disease, or known CNS disease.
  • Known Gilbert's syndrome
  • 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.
  • For patients enrolling onto Arm D (MM-398 with 5-FU and leucovorin)
  • Prior irinotecan treatment
  • Arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) < 6 months prior to enrollment
  • Known hypersensitivity to any of the components of MM-398, other liposomal products, fluoropyrimidines or leucovorin
  • Known dihydropyrimidine dehydrogenase (DPD) deficiency

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Texas Oncology - Austin Midtown

    Austin, Texas, 78705

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • Indiana University Health Goshen Center for Cancer Care

    Goshen, Indiana, 46526

  • Comprehensive Cancer Centers of Nevada

    Henderson, Nevada, 89014

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • The University of Tennessee Medical Center

    Knoxville, Tennessee, 37920

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Texas Oncology - SAT&BC

    San Antonio, Texas, 78216

Other trials in United States

About this study

Official title: A Phase Ib Clinical Study of BBI608 in Combination With Standard Chemotherapies in Adult Patients With Metastatic Pancreatic Adenocarcinoma

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.

Read the 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.

Keywords
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
Medical subject headings
Digestive System Neoplasms, Endocrine Gland Neoplasms, Pancreatic Neoplasms, Pancreatic cancer, adult, Pancreatic Diseases, Adenoma, Islet Cell, Carcinoma, Islet Cell, Carcinoma, Pancreatic Ductal

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BBI608Drug

    Also called Napabucasin, BB608, BBI-608

    Administered continuously twice daily with doses separated by 12 hours

  • Nab-paclitaxelDrug

    Also called Abraxane, nanoparticle albumin-bound paclitaxel, paclitaxel, ABI-007

    Nab-paclitaxel 125 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine 1000 mg/m^2 I.V. infusion on Days 1, 8, and 15 of every 28-day cycle

  • OxaliplatinDrug

    Also called Eloxatin

    Oxaliplatin 85 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle

  • LeucovorinDrug

    Also called Folinic Acid

    Arm C, D: Leucovorin 400 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle

  • IrinotecanDrug

    Also called Camptosar

    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

  • FluorouracilDrug

    Also called 5-FU, Carac, Efudex, Fluoroplex

    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

  • MM-398Drug

    Also called Onivyde

    MM-398 70 mg/m^2 I.V. infusion on Days 1 and 15 of every 28-day cycle

Study groups in NCT02231723
Study groupRoleWhat they receive
A: BBI608 in combination with Gemcitabine and nab-PaclitaxelExperimentalNot described
Receives: Drug: BBI608; Drug: Nab-paclitaxel; Drug: Gemcitabine
B: BBI608 in combination with modified FOLFIRINOXExperimentalNot described
Receives: Drug: BBI608; Drug: Oxaliplatin; Drug: Irinotecan; Drug: Fluorouracil
C: BBI608 in combination with FOLFIRIExperimentalNot described
Receives: Drug: BBI608; Drug: Leucovorin; Drug: Irinotecan; Drug: Fluorouracil
D: BBI608 in combination with MM-398, 5-FU and leucovorinExperimentalNot described
Receives: Drug: BBI608; Drug: Leucovorin; Drug: Fluorouracil; Drug: MM-398

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety by reporting the adverse events and serious adverse events

    Measured: 6 months

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

    Measured: 3 months

Secondary outcomes (4)

  1. Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing tumor assessments every 8 weeks

    Measured: 6 months

  2. Assess the preliminary anti-tumor activity of BBI608 when administered in combination with standard chemotherapies by performing serum CA 19-9 level measurement

    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

    Measured: 6 months

  3. Assess pharmacokinetic profile of BBI608 when administered in combination with standard chemotherapies

    Blood sampling to assess the pharmacokinetic profile (Area under the curve) of BBI608.

    Measured: 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

  4. Assess pharmacodynamic activity of BBI608 when administered in combination with standard chemotherapies

    Tumor Biopsy to provide information of the biomarkers by histopathology and Cancer Stem Cell assays.

    Measured: During the first 28 days of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Sep 2014 (estimated)
  2. Study startAug 2014
  3. Primary completionJun 2020
  4. Study completionJun 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
139 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02231723
Sponsor's protocol ID
BBI608-118
Other IDs
BBI608-201PANC
Status last verified
Apr 2022
First submitted
30 Aug 2014
Last updated
18 Nov 2023
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BBI608, Nab-paclitaxel and Gemcitabine in people with Metastatic Pancreatic Adenocarcinoma, run by Sumitomo Pharma America, Inc. at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety by reporting the adverse events and serious adverse events (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02231723.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.

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