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

Pancreatic Cancer Clinical Trial

Official title:

Phase I Study of Lonsurf in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Advanced Pancreatic Ductal Adenocarcinoma (PDAC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04046887
• Other study ID #: IUSCC-0664
• Status: Terminated
• Phase: Phase 1
• Start date: September 11, 2019
• Est. completion date: October 4, 2023

Study information

• Verified date: January 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: October 4, 2023
• Est. primary completion date: May 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Cancer
• Pancreatic Ductal Adenocarcinoma
• Pancreatic Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Indiana University Melvin & Bren Simon Cancer Center	Indianapolis	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
Patrick Joseph Loehrer Sr.	Indiana University, Taiho Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Dose Limiting Toxicities (DLTs)	Number of DLTs observed	28 days (Cycle 1)
Secondary	Frequency of adverse events in the safety evaluable population	safety and toxicity data will be assessed using NCI CTCAE v5.0	from start of treatment until 30 days after treatment discontinuation (i.e up to 2 years)
Secondary	Response rate to the combination of lonsurf, gemcitabine, and nab-paclitaxel in the efficacy evaluable population	Using RECIST 1.1	from start of treatment until treatment discontinuation (i.e. up to 2 years)
Secondary	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)
Secondary	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)
Secondary	Disease control rate (DCR)	Disease control rate (DCR) as defined by (complete response + partial response + stable disease)	8 weeks
Secondary	European Organization for Research and Treatment of Cancer quality of life questionnaire	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.	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)