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

NCT04046887 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: IUSCC-0664
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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)

Conditions

Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Keywords

Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer; Metastatic Pancreatic Cancer; Locally Advanced Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Frequency of Dose Limiting Toxicities (DLTs)

  Number of DLTs observed

  28 days (Cycle 1)

Secondary Outcomes (6)

• Frequency of adverse events in the safety evaluable population

  from start of treatment until 30 days after treatment discontinuation (i.e up to 2 years)

• Response rate to the combination of lonsurf, gemcitabine, and nab-paclitaxel in the efficacy evaluable population

  from start of treatment until treatment discontinuation (i.e. up to 2 years)

• Median Overall Survival (mOS) of the treated population

  from start of treatment until death or last known follow up (i.e up to 2 years)

• Median Progression-free Survival (mPFS) of the treated population

  from start of treatment until disease progression or last follow up (i.e. up to 2 years)

• Disease control rate (DCR)

  8 weeks

Study Arms (1)

Combination of lonsurf + gemcitabine + nab-paclitaxel

EXPERIMENTAL

Drug: Lonsurf; Drug: Gemcitabine; Drug: Nab-Paclitaxel

Interventions

Lonsurf DRUG

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.

Combination of lonsurf + gemcitabine + nab-paclitaxel

Gemcitabine DRUG

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.

Combination of lonsurf + gemcitabine + nab-paclitaxel

Nab-Paclitaxel DRUG

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.

Combination of lonsurf + gemcitabine + nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years old at the time of informed consent
• Ability to provide written informed consent and HIPAA authorization
• 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)
• Histologically or cytologically confirmed PDAC
• Confirmed PDAC that is measurable or evaluable per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Gastrointestinal symptoms (nausea, vomiting, and diarrhea) of Grade 1 or less
• Adequate organ function as defined by:
• Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x upper limits of normal (ULN)
• Total bilirubin level ≤ 1.5 x ULN
• 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).
• Hemoglobin (Hgb) ≥ 9 g/dl
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Acceptable coagulation studies as demonstrated by prothrombin time (PT) within normal limits (+/-15%) unless they are on anticoagulation therapy

You may not qualify if:

• Neuropathy \> Grade 1 at baseline
• Prior systemic chemotherapy for any other malignancy (aside from adjuvant therapy for PDAC) in the last 3 years
• 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)
• Prior exposure to nab-paclitaxel, paclitaxel, or other taxanes
• History of bowel obstruction in the preceding 3 months of therapy, including gastric outlet obstruction related to PDAC
• Large, uncontrolled ascites requiring paracentesis
• Major surgery, other than diagnostic or laparoscopic surgery, within 4 weeks prior to first dose. (Port placement would not be considered a surgery.)
• Any known untreated brain metastases including leptomeningeal metastases
• 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)
• Uncontrolled chronic diarrhea \> Grade 1 at baseline.
• 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.
• Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• History of posterior reversible encephalopathy syndrome
• Enrollment on any additional investigational agent study

Sponsors & Collaborators

• Patrick Joseph Loehrer Sr.: lead
• Indiana University: collaborator
• Taiho Oncology, Inc.: collaborator

Study Sites (1)

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

trifluridine tipiracil drug combination; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Patrick J Loehrer, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Distinguished Professor of Medicine

Model Details: 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.

Study Record Dates

• First Submitted: August 1, 2019
• First Posted: August 6, 2019
• Study Start: September 11, 2019
• Primary Completion: May 10, 2021
• Study Completion: October 4, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Locations

US (1)