A Study of the Safety and PK of PCS6422 (Eniluracil) with Capecitabine in Patients with Advanced, Refractory GI Tract Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer; Refractory Cancer; Tumor Gastric
• Intervention / Treatment: Drug: PCS6422 and capecitabine

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Processa Clinical Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Processa Clinical Site
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Processa Clinical Site
  • New York
    • New York, New York, United States, 10467
      • Processa Clinical Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Processa Clinical Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Processa Clinical Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Has measurable disease in accordance with Respond Evaluation Criteria in Solid Tumors (RECIST) guidelines (Version 1.1).
3. Is aged ≥18 years
4. Has not received treatment with intravenous (IV) 5 FU or oral 5 FU analogs in the 4 weeks preceding enrollment
5. Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 at study entry

6. Has adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment:

   1. peripheral ANC of ≥1.5 × 109/L
   2. platelet count of ≥75 × 109/L without growth factor/transfusion
   3. hemoglobin ≥8.5 g/dL without growth factor/transfusion
   4. estimated glomerular filtration rate >50 mL/min
   5. 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
   6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN, with liver metastasis <5 × ULN
   7. international normalized ratio (INR) <1.5
7. Has a life expectancy of at least 12 weeks
8. 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
9. Females of childbearing potential must have a negative serum β human chorionic gonadotropin pregnancy test result
10. Willingly provides written, informed consent.
11. Has resolution or stabilization of acute toxicity from prior therapy to Grade <2 - except Grade 2 neuropathy
12. If patient has human immune deficiency virus (HIV) infection, it is controlled with undetectable viral load with antiretroviral treatment.
13. If patient has hepatitis C infection and received antiviral treatment, has a negative viral load at Screening
14. If patient has chronic hepatitis B infection and is receiving antiviral treatment, has a negative viral load at Screening.
15. Is willing and able to comply with all protocol required visits and assessments

Exclusion Criteria:

1. Is unable to take oral medication or malabsorption syndromes potentially interfering with medication absorption (e.g., short bowel syndrome or chronic, partial bowel obstruction)
2. Has history or presence of clinically significant abnormal 12 lead ECG results, in the investigator's opinion
3. Has current brain metastasis
4. Has prolonged QTc (with Fridericia's correction) of >480 msec in men and women performed at Screening
5. 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
6. Has congenital long QT syndrome or a family history of long QT syndrome
7. 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
8. Has an electrolyte disturbance, such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, or hypocalcemia. Patients can be enrolled following successful correction of an electrolyte disturbance.
9. Is currently using any drugs included in the prohibited medications list in the protocol (including those that can prolong QTc) that cannot be discontinued
10. Has known hypersensitivity to any of the components of study treatments
11. 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
12. Is a pregnant or lactating female
13. Had major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to the first dose of study treatment
14. Is receiving or has received any investigational treatment within 4 weeks prior to study entry, or participating in another clinical study
15. Has known DPD deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCS6422 + Capecitabine; Fixed dose of PCS6422 combined with various doses of Capecitabine administered in 14 day cycles	Drug: PCS6422 and capecitabine; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	~6 months
Maximum Plasma Concentration (Cmax) of capecitabine	To evaluate the Maximum Plasma Concentration (Cmax) of capecitabine	~14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QTc effect of PCS6422	To evaluate the effect of PCS6422 on QTc	~6 months
Maximum Plasma Concentration (Cmax) of PCS6422	To evaluate the Maximum Plasma Concentration (Cmax) of PCS6422	~14 days
Number of participants with Adverse Events of Special Interest (AESI)	Frequency, duration and severity of AESIs	~6 months

Collaborators and Investigators

• Sponsor: Processa Pharmaceuticals
• Investigators: Study Director: Sian Bigora, Pharm. D, Processa Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Actual): June 12, 2024
• Study Completion (Actual): September 9, 2024

Study Registration Dates

• First Submitted: April 23, 2021
• First Submitted That Met QC Criteria: April 23, 2021
• First Posted (Actual): April 27, 2021

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Capecitabine; Eniluracil
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: PCS6422-GI-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No