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

NCT ID: NCT04046887

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-11
• Study Completion Date: 2023-10-04

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)

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

Conditions

Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination of lonsurf + gemcitabine + nab-paclitaxel

Group Type: EXPERIMENTAL

Lonsurf

Intervention Type: 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.

Gemcitabine

Intervention Type: 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.

Nab-Paclitaxel

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: collaborator

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: collaborator

Patrick Joseph Loehrer Sr.

OTHER

Sponsor Role: lead

Responsible Party

Patrick Joseph Loehrer Sr.

Distinguished Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Patrick J Loehrer, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

Indiana University Melvin & Bren Simon Cancer Center

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

IUSCC-0664

Identifier Type: -

Identifier Source: org_study_id