A Study of the Safety and PK of PCS6422 (Eniluracil) With Capecitabine in Patients With Advanced, Refractory GI Tract Tumors
Primary Purpose
Advanced Cancer, Refractory Cancer, Tumor Gastric
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PCS6422 and capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Cancer focused on measuring Capecitabine, Eniluracil
Eligibility Criteria
Inclusion Criteria:
- Has advanced, metastatic or unresectable GI tract tumors that are refractory or intolerant to existing available therapies and for whom the investigator recommends fluoropyrimidine monotherapy.
- Has measurable disease in accordance with Respond Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1).
- Is aged ≥18 years
- Has not received treatment with intravenous (IV) 5 FU or oral 5 FU analogs in the 4 weeks preceding enrollment
- Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 at study entry
Has adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment:
- peripheral ANC of ≥1.5 × 109/L
- platelet count of ≥75 × 109/L without growth factor/transfusion
- hemoglobin ≥8.5 g/dL without growth factor/transfusion
- estimated glomerular filtration rate >50 mL/min
- total bilirubin <2 × upper limit of normal (ULN); <5 × ULN if patient has liver metastases, biliary tract cancer; or ≤3 × ULN if the patient has Gilbert's disease
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN, with liver metastasis <5 × ULN
- international normalized ratio (INR) <1.5
- Has a life expectancy of at least 12 weeks
- Female patients of childbearing potential and male patients with partners capable of reproduction must agree to use an effective contraceptive method from the time of Screening through 60 days after the last dose of capecitabine
- Females of childbearing potential must have a negative serum β human chorionic gonadotropin pregnancy test result
- Willingly provides written, informed consent.
- Has resolution or stabilization of acute toxicity from prior therapy to Grade <2 - except Grade 2 neuropathy
- If patient has human immune deficiency virus (HIV) infection, it is controlled with undetectable viral load with antiretroviral treatment.
- If patient has hepatitis C infection and received antiviral treatment, has a negative viral load at Screening
- If patient has chronic hepatitis B infection and is receiving antiviral treatment, has a negative viral load at Screening.
- Is willing and able to comply with all protocol required visits and assessments
Exclusion Criteria:
- Is unable to take oral medication or malabsorption syndromes potentially interfering with medication absorption (e.g., short bowel syndrome or chronic, partial bowel obstruction)
- Has history or presence of clinically significant abnormal 12 lead ECG results, in the investigator's opinion
- Has current brain metastasis
- Has prolonged QTc (with Fridericia's correction) of >480 msec in men and women performed at Screening
- Has a history of prolonged QTc interval, ventricular tachycardia/fibrillation or significant ventricular arrhythmia, or Torsades de Pointes, or a history of ventricular ablation for arrhythmia
- Has congenital long QT syndrome or a family history of long QT syndrome
- Has other clinically significant cardiac disease including, but not limited to, uncontrolled angina, myocardial ischemia or infarction within 6 months, congestive heart failure >Class II per the New York Heart Association, or history of myocarditis
- Has an electrolyte disturbance, such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, or hypocalcemia. Patients can be enrolled following successful correction of an electrolyte disturbance.
- Is currently using any drugs included in the prohibited medications list in the protocol (including those that can prolong QTc) that cannot be discontinued
- Has known hypersensitivity to any of the components of study treatments
- Has other primary cancer requiring treatment within the last 3 years, except for cervical intraepithelial neoplasia, ductal carcinoma in situ, or completely excised squamous or basal cell carcinoma
- Is a pregnant or lactating female
- Had major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to the first dose of study treatment
- Is receiving or has received any investigational treatment within 4 weeks prior to study entry, or participating in another clinical study
- Has known DPD deficiency
Sites / Locations
- Processa Clinical SiteRecruiting
- Processa Clinical SiteRecruiting
- Processa Clinical Site
- Processa Clinical SiteRecruiting
- Processa Clinical SiteRecruiting
- Processa Clinical SiteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PCS6422 + Capecitabine
Arm Description
Fixed dose of PCS6422 combined with various doses of Capecitabine administered in 14 day cycles
Outcomes
Primary Outcome Measures
Number of participants with dose limiting toxicities (DLT) and incidence of adverse events as assessed by CTCAE v5.0
Frequency, duration, and severity of DLTs and adverse events (AEs)
Maximum Plasma Concentration (Cmax) of capecitabine
To evaluate the Maximum Plasma Concentration (Cmax) of capecitabine
Secondary Outcome Measures
QTc effect of PCS6422
To evaluate the effect of PCS6422 on QTc
Maximum Plasma Concentration (Cmax) of PCS6422
To evaluate the Maximum Plasma Concentration (Cmax) of PCS6422
Number of participants with Adverse Events of Special Interest (AESI)
Frequency, duration and severity of AESIs
Full Information
NCT ID
NCT04861987
First Posted
April 23, 2021
Last Updated
August 10, 2023
Sponsor
Processa Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04861987
Brief Title
A Study of the Safety and PK of PCS6422 (Eniluracil) With Capecitabine in Patients With Advanced, Refractory GI Tract Tumors
Official Title
A Phase 1b Dose-escalation Study of the Safety and Pharmacokinetics of Fixed-dose PCS6422 With Escalating Doses of Capecitabine Administered Orally to Patients With Advanced, Refractory Gastrointestinal Tract Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 18, 2021 (Actual)
Primary Completion Date
September 20, 2023 (Anticipated)
Study Completion Date
March 10, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Processa Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is an open label, multicenter study in patients who have advanced, relapsed refractory GI cancer or are not relapsed/refractory but are intolerant to other therapies who, in the judgment of investigators, are candidates for fluoropyrimidine monotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Cancer, Refractory Cancer, Tumor Gastric
Keywords
Capecitabine, Eniluracil
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PCS6422 + Capecitabine
Arm Type
Experimental
Arm Description
Fixed dose of PCS6422 combined with various doses of Capecitabine administered in 14 day cycles
Intervention Type
Drug
Intervention Name(s)
PCS6422 and capecitabine
Intervention Description
PCS6422 is an experimental drug that, when combined with capecitabine, may make the immune response more active against cancer. Capecitabine is a commonly used oral fluoropyrimidine.
Primary Outcome Measure Information:
Title
Number of participants with dose limiting toxicities (DLT) and incidence of adverse events as assessed by CTCAE v5.0
Description
Frequency, duration, and severity of DLTs and adverse events (AEs)
Time Frame
~6 months
Title
Maximum Plasma Concentration (Cmax) of capecitabine
Description
To evaluate the Maximum Plasma Concentration (Cmax) of capecitabine
Time Frame
~14 days
Secondary Outcome Measure Information:
Title
QTc effect of PCS6422
Description
To evaluate the effect of PCS6422 on QTc
Time Frame
~6 months
Title
Maximum Plasma Concentration (Cmax) of PCS6422
Description
To evaluate the Maximum Plasma Concentration (Cmax) of PCS6422
Time Frame
~14 days
Title
Number of participants with Adverse Events of Special Interest (AESI)
Description
Frequency, duration and severity of AESIs
Time Frame
~6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has advanced, metastatic or unresectable GI tract tumors that are refractory or intolerant to existing available therapies and for whom the investigator recommends fluoropyrimidine monotherapy.
Has measurable disease in accordance with Respond Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1).
Is aged ≥18 years
Has not received treatment with intravenous (IV) 5 FU or oral 5 FU analogs in the 4 weeks preceding enrollment
Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 at study entry
Has adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment:
peripheral ANC of ≥1.5 × 109/L
platelet count of ≥75 × 109/L without growth factor/transfusion
hemoglobin ≥8.5 g/dL without growth factor/transfusion
estimated glomerular filtration rate >50 mL/min
total bilirubin <2 × upper limit of normal (ULN); <5 × ULN if patient has liver metastases, biliary tract cancer; or ≤3 × ULN if the patient has Gilbert's disease
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN, with liver metastasis <5 × ULN
international normalized ratio (INR) <1.5
Has a life expectancy of at least 12 weeks
Female patients of childbearing potential and male patients with partners capable of reproduction must agree to use an effective contraceptive method from the time of Screening through 60 days after the last dose of capecitabine
Females of childbearing potential must have a negative serum β human chorionic gonadotropin pregnancy test result
Willingly provides written, informed consent.
Has resolution or stabilization of acute toxicity from prior therapy to Grade <2 - except Grade 2 neuropathy
If patient has human immune deficiency virus (HIV) infection, it is controlled with undetectable viral load with antiretroviral treatment.
If patient has hepatitis C infection and received antiviral treatment, has a negative viral load at Screening
If patient has chronic hepatitis B infection and is receiving antiviral treatment, has a negative viral load at Screening.
Is willing and able to comply with all protocol required visits and assessments
Exclusion Criteria:
Is unable to take oral medication or malabsorption syndromes potentially interfering with medication absorption (e.g., short bowel syndrome or chronic, partial bowel obstruction)
Has history or presence of clinically significant abnormal 12 lead ECG results, in the investigator's opinion
Has current brain metastasis
Has prolonged QTc (with Fridericia's correction) of >480 msec in men and women performed at Screening
Has a history of prolonged QTc interval, ventricular tachycardia/fibrillation or significant ventricular arrhythmia, or Torsades de Pointes, or a history of ventricular ablation for arrhythmia
Has congenital long QT syndrome or a family history of long QT syndrome
Has other clinically significant cardiac disease including, but not limited to, uncontrolled angina, myocardial ischemia or infarction within 6 months, congestive heart failure >Class II per the New York Heart Association, or history of myocarditis
Has an electrolyte disturbance, such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, or hypocalcemia. Patients can be enrolled following successful correction of an electrolyte disturbance.
Is currently using any drugs included in the prohibited medications list in the protocol (including those that can prolong QTc) that cannot be discontinued
Has known hypersensitivity to any of the components of study treatments
Has other primary cancer requiring treatment within the last 3 years, except for cervical intraepithelial neoplasia, ductal carcinoma in situ, or completely excised squamous or basal cell carcinoma
Is a pregnant or lactating female
Had major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to the first dose of study treatment
Is receiving or has received any investigational treatment within 4 weeks prior to study entry, or participating in another clinical study
Has known DPD deficiency
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mary Nyberg
Phone
443-776-3133
Email
mnyberg@processapharmaceuticals.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sian Bigora, Pharm. D
Organizational Affiliation
Processa Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Processa Clinical Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debbie Vidlak
Phone
402-559-7507
Email
dvidlak@unmc.edu
First Name & Middle Initial & Last Name & Degree
Jean Grem, MD
Facility Name
Processa Clinical Site
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ahsan Khan
Phone
732-235-3458
Email
ark140@cinj.rutgers.edu
First Name & Middle Initial & Last Name & Degree
Patrick Boland, MD
Facility Name
Processa Clinical Site
City
Santa Fe
State/Province
New Mexico
ZIP/Postal Code
87505
Country
United States
Individual Site Status
Completed
Facility Name
Processa Clinical Site
City
New York
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohammed Ghalib
Phone
718-405-8527
Email
mhghalib@montefiore.org
First Name & Middle Initial & Last Name & Degree
Eric Feldman, MD
Facility Name
Processa Clinical Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celestine Slapnicker
Phone
216-286-3369
Email
celestine.slapnicker@UHhospitals.org
First Name & Middle Initial & Last Name & Degree
Amit Mahipal, MD
Facility Name
Processa Clinical Site
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharon Goldberg
Email
sharon.goldberg@usoncology.com
First Name & Middle Initial & Last Name & Degree
Alexander Spira, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of the Safety and PK of PCS6422 (Eniluracil) With Capecitabine in Patients With Advanced, Refractory GI Tract Tumors
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