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Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced (PDAC)

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. Read our disclaimer for details. Identifier: NCT04046887
Recruitment Status : Active, not recruiting
First Posted : August 6, 2019
Last Update Posted : April 14, 2022
Indiana University
Taiho Oncology, Inc.
Information provided by (Responsible Party):
Patrick Joseph Loehrer Sr., Indiana University

Brief Summary:
The purpose of this study is to determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel in Pancreatic ductal adenocarcinoma (PDAC)

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Pancreatic Ductal Adenocarcinoma Drug: Lonsurf Drug: Gemcitabine Drug: Nab-Paclitaxel Phase 1

Detailed Description:

This is a single-institution, prospective, phase I dose escalation trial of lonsurf combined with gemcitabine and nab-paclitaxel using the 3+3 design. This study will enroll 18 patients over 12-15 months.

Primary Objective To determine the recommended phase 2 dose (RP2D) of the combination of lonsurf, gemcitabine and nab-paclitaxel

Secondary Objectives

  1. Examine safety and toxicity of the combination
  2. Estimate response rate to the combination
  3. Estimate median overall survival (mOS) of the treated population
  4. Estimate median progression free survival (mPFS) of the treated population
  5. Estimate disease control rate (DCR) at 8 weeks
  6. Evaluate quality of life while receiving the combination therapy

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

Initially 3 patients will be enrolled to the starting cohort. If 1 of 3 patients experience a dose-limiting toxicity (DLT) in the first cycle, then an additional 3 evaluable patients will be accrued to that dose level. Dose reductions are not permitted during cycle 1. If 2 or more patients in a cohort experience a DLT, then the previous dose will be considered the recommended phase 2 dose (PR2D) and dose escalation will terminate. Dose escalation will proceed according to the scheme above only after all patients (3 or 6 evaluable patients, depending on the incidence of DLT) have been followed for at least 1 full cycle.

Once dose escalation has been completed, if only 2 dose levels were used to determine the RP2D and depending on how many patients were replaced, additional patients will be enrolled at the RP2D in order to obtain data for 18 patients total.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Pancreatic Ductal Adenocarcinoma (PDAC)
Actual Study Start Date : August 15, 2019
Actual Primary Completion Date : May 10, 2021
Estimated Study Completion Date : May 2025

Arm Intervention/treatment
Experimental: Combination of lonsurf + gemcitabine + nab-paclitaxel Drug: Lonsurf
Lonsurf will be administered orally twice a day on days 2-6 and 16-20 of every 28-day cycle at a dose of 25 mg/m2, 20 mg/m2 or 30 mg/m2 depending on cohort assignment.

Drug: Gemcitabine
Gemcitabine will be intravenously administered on Days 1 and 15 of every 28-day cycle at a dose of 800 mg/m2, 600 mg/m2 or 1000 mg/m2 depending on cohort assignment.

Drug: Nab-Paclitaxel
Nab-Paclitaxel will be intravenously administered on Days 1 and 15 of every 28-day cycle at a dose of 100 mg/m2, 75 mg/m2 or 125 mg/m2 depending on cohort assignment.

Primary Outcome Measures :
  1. Frequency of Dose Limiting Toxicities (DLTs) [ Time Frame: 28 days (Cycle 1) ]
    Number of DLTs observed

Secondary Outcome Measures :
  1. Frequency of adverse events in the safety evaluable population [ Time Frame: from start of treatment until 30 days after treatment discontinuation (i.e up to 2 years) ]
    safety and toxicity data will be assessed using NCI CTCAE v5.0

  2. Response rate to the combination of lonsurf, gemcitabine, and nab-paclitaxel in the efficacy evaluable population [ Time Frame: from start of treatment until treatment discontinuation (i.e. up to 2 years) ]
    Using RECIST 1.1

  3. Median Overall Survival (mOS) of the treated population [ Time Frame: from start of treatment until death or last known follow up (i.e up to 2 years) ]
  4. Median Progression-free Survival (mPFS) of the treated population [ Time Frame: from start of treatment until disease progression or last follow up (i.e. up to 2 years) ]
  5. Disease control rate (DCR) [ Time Frame: 8 weeks ]
    Disease control rate (DCR) as defined by (complete response + partial response + stable disease)

  6. European Organization for Research and Treatment of Cancer quality of life questionnaire [ Time Frame: Day 1 of each cycle(each cycle is 28 days),from start of treatment until disease progression or discontinuation of treatment (i.e. up to 2 years) ]
    Scale scores were calculated by averaging items within scales and transforming average scores linearly. All of the scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. ≥ 18 years old at the time of informed consent
  2. Ability to provide written informed consent and HIPAA authorization
  3. Untreated locally advanced Pancreatic Ductal Adenocarcinoma (PDAC) as defined by National Comprehensive Cancer Network (NCCN) guidelines or, untreated metastatic PDAC (prior adjuvant therapy is permitted if it's been greater than 6 months since completion)
  4. Histologically or cytologically confirmed PDAC
  5. Confirmed PDAC that is measurable or evaluable per RECIST 1.1
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  7. Gastrointestinal symptoms (nausea, vomiting, and diarrhea) of Grade 1 or less
  8. Adequate organ function as defined by:

    1. Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x upper limits of normal (ULN)
    2. Total bilirubin level ≤ 1.5 x ULN
    3. Creatinine level < 1.0 x ULN or creatinine clearance > 60 mL/min/1.73 m2 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/m2, lean body weight should be used to calculate the glomerular filtration rate (GFR).
    4. Hemoglobin (Hgb) ≥ 9 g/dl
    5. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    6. Platelets ≥ 100 x 109/L
    7. Acceptable coagulation studies as demonstrated by prothrombin time (PT) within normal limits (+/-15%) unless they are on anticoagulation therapy
  9. Life expectancy estimated at ≥ 3 months
  10. Women of childbearing potential definition (WOCBP) must have a negative serum or urine pregnancy test performed within 14 days prior to initiation of study treatment.

    Any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) is classified as WOCBP if she meets the following criteria:

    1. Has not undergone a hysterectomy or bilateral oophorectomy; or
    2. Has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months).
  11. WOCBP and men must agree to use adequate contraception prior, to study entry, for the duration of study participation, and 8 weeks after the end of treatment.

Exclusion Criteria:

  1. Neuropathy > Grade 1 at baseline
  2. Prior systemic chemotherapy for any other malignancy (aside from adjuvant therapy for PDAC) in the last 3 years
  3. Active malignancy other than PDAC (other than adequately treated cervical or vulvar carcinoma in situ, treated basal cell or squamous carcinoma of the skin, superficial bladder tumors (Ta, Tis & T1), ductal carcinoma in situ (DCIS) of the breast and low grade prostate cancer. Any cancer curatively treated >3 years prior to entry with no clinical evidence of recurrence is permitted)
  4. Prior exposure to nab-paclitaxel, paclitaxel, or other taxanes
  5. History of bowel obstruction in the preceding 3 months of therapy, including gastric outlet obstruction related to PDAC
  6. Large, uncontrolled ascites requiring paracentesis
  7. Major surgery, other than diagnostic or laparoscopic surgery, within 4 weeks prior to first dose. (Port placement would not be considered a surgery.)
  8. Any known untreated brain metastases including leptomeningeal metastases
  9. Pregnant or breastfeeding
  10. 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)
  11. Uncontrolled chronic diarrhea > Grade 1 at baseline.
  12. Uncontrolled intercurrent illness including, but not limited to uncontrolled active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, significant pulmonary disease, uncontrolled infection, or psychiatric illness/social situations that would limit compliance with study requirements.
  13. Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  14. History of posterior reversible encephalopathy syndrome
  15. Enrollment on any additional investigational agent study
  16. Known hypersensitivity to gemcitabine or taxanes
  17. Significant cardiac disease including the following: unstable angina, New York Heart Association class III-IV congestive heart failure, myocardial infarction < 6 months prior to study enrollment
  18. History of hemolytic-uremic syndrome
  19. Known infection with Human Immunodeficiency Virus (HIV) and/or active infection with hepatitis B or hepatitis C

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 identifier (NCT number): NCT04046887

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United States, Indiana
Indiana University Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Patrick Joseph Loehrer Sr.
Indiana University
Taiho Oncology, Inc.
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Principal Investigator: Patrick J Loehrer, MD Indiana University
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Responsible Party: Patrick Joseph Loehrer Sr., Distinguished Professor of Medicine, Indiana University Identifier: NCT04046887    
Other Study ID Numbers: IUSCC-0664
First Posted: August 6, 2019    Key Record Dates
Last Update Posted: April 14, 2022
Last Verified: April 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Patrick Joseph Loehrer Sr., Indiana University:
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Metastatic Pancreatic Cancer
Locally Advanced Pancreatic Cancer
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs