Back to resultsYF476 and Type II Gastric Carcinoids
Primary Purpose
Zollinger-Ellison Syndrome
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
YF476
Sponsored by
About this trial
This is an interventional treatment trial for Zollinger-Ellison Syndrome focused on measuring YF476, netazepide, gastric carcinoids, Zollinger-Ellison syndrome
Eligibility Criteria
Inclusion criteria:
- Men; post-menopausal women; pre-menopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy; or pre-menopausal women using one of the allowed methods of contraception: condom and spermicide or intra-uterine device.
- Patients with serum gastrin >250 pg/mL.
- Hepatic function: AST and ALT ≤2.0 x ULN; total bilirubin ≤1.0 x ULN.
- Renal function: serum creatinine <1.0 x ULN.
- Haematologic function: Hb ≥10.0 g/dL; WBC ≥3.5 x 10e9 /L; ANC ≥1.5 x 10e9 /L; platelets ≥100 x 10e9 /L.
- Coagulation parameters: INR or PT ≤1.0 x ULN; PTT ≤1.0 x ULN.
- Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
- Willingness to give fully-informed, written consent.
Exclusion criteria:
- Patients under 18 years.
- Women who are pregnant, lactating or using a steroid contraceptive.
- Prior gastric resection or bypass.
- Planned gastrinoma resection during the study period.
- Patients on somatostatin analogues, except for those on therapy for >6 months with stable or worsening carcinoids.
- Inability to tolerate endoscopy, or refusal of endoscopy.
- Physical findings, ECG (especially prolonged QTc interval >450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
- Certain medicines and herbal remedies taken during the 7 days before visit 2.
- Participation in a trial of an IMP within the previous 28 days.
- Presence of drug or alcohol abuse.
History or baseline findings of:
- type 1 diabetes mellitus;
- pancreatitis (baseline amylase and/or >2.0 x ULN);
- hepatitis B, hepatitis C or HIV;
- malabsorption syndrome or inability to swallow or retain oral medicine;
- major surgery <28 days prior to enrolment;
- ECOG performance status >2; or
- another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in-situ.
- Also, any clinically significant and uncontrolled major morbidity including but not limited to; serious cardiac disease (unstable angina, s/p myocardial infarction <1 month); respiratory disease (advanced COPD or pulmonary fibrosis); uncontrolled hypertension; or active systemic infection.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Eligible patients
Arm Description
The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.
Outcomes
Primary Outcome Measures
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids. For each participant, three gastric carcinoids were identified and measured at baseline. The same gastric carcinoids were then measured at the Week 12 visit and the percentage difference in size from baseline calculated. The mean percentage change of the three gastric carcinoids per participant is recorded.
A Reduction of 25% in the Gastric ECL Cell Density.
A reduction of 25% in the gastric ECL cell density.
Secondary Outcome Measures
Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples
The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured.
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
Volume of aspirate (mL)
Acid in aspirate (mEq)
Acid output (mEq)
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR
Assessed by quantitative PCR.
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument
Assessed by the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) instrument. Patients assessed a total of 10 symptoms on a scale of 0-5 where: 0 = no symptoms; 1 = symptoms noticeable, but not bothersome; 2 = symptoms noticeable and bothersome, but not every day; 3 = symptoms bothersome everyday; 4 = symptoms affect daily activities; and 5 = symptoms are incapacitating (unable to do daily activities). The total score was summed and reported. The maximum obtainable total score was 50 and minimum obtainable total score was 0, with higher scores indicating a worse outcome and lower scores indicating a better outcome.
Safety and Tolerability
Assessed by monitoring adverse events reported by patients
Circulating Plasma Concentration of Gastrin
The level of gastrin biomarkers circulating in the blood was measured.
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
Volume of aspirate (mL)
Acid in aspirate (mEq)
Acid output (mEq)
Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
Volume of aspirate (mL)
Acid in aspirate (mEq)
Acid output (mEq)
Full Information
NCT ID
NCT02454075
First Posted
May 13, 2015
Last Updated
January 28, 2021
Sponsor
Trio Medicines Ltd.
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT02454075
Brief Title
YF476 and Type II Gastric Carcinoids
Official Title
A Pilot Trial of YF476, a Gastrin Antagonist, in Patients With Type II Gastric Carcinoids Associated With Zollinger-Ellison Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Poor recruitment
Study Start Date
April 11, 2011 (Actual)
Primary Completion Date
June 22, 2012 (Actual)
Study Completion Date
June 22, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trio Medicines Ltd.
Collaborators
National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate whether treatment with YF476 is safe and effective in reducing the size of type II gastric carcinoid tumours, or limiting the abnormal growth of gastric ECL cells, in patients with Zollinger-Ellison syndrome.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Zollinger-Ellison Syndrome
Keywords
YF476, netazepide, gastric carcinoids, Zollinger-Ellison syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Eligible patients
Arm Type
Experimental
Arm Description
The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia.
Intervention Type
Drug
Intervention Name(s)
YF476
Other Intervention Name(s)
Netazepide
Intervention Description
Gastrin receptor antagonist
Primary Outcome Measure Information:
Title
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Description
Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids. For each participant, three gastric carcinoids were identified and measured at baseline. The same gastric carcinoids were then measured at the Week 12 visit and the percentage difference in size from baseline calculated. The mean percentage change of the three gastric carcinoids per participant is recorded.
Time Frame
Week 12 visit
Title
A Reduction of 25% in the Gastric ECL Cell Density.
Description
A reduction of 25% in the gastric ECL cell density.
Time Frame
Week 12 visit
Secondary Outcome Measure Information:
Title
Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Description
Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.
Time Frame
Week 12 visit
Title
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples
Description
The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured.
Time Frame
Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Title
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate
Description
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
Volume of aspirate (mL)
Acid in aspirate (mEq)
Acid output (mEq)
Time Frame
Week 2 visit (baseline) and Week 6 visit
Title
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR
Description
Assessed by quantitative PCR.
Time Frame
Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Title
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument
Description
Assessed by the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) instrument. Patients assessed a total of 10 symptoms on a scale of 0-5 where: 0 = no symptoms; 1 = symptoms noticeable, but not bothersome; 2 = symptoms noticeable and bothersome, but not every day; 3 = symptoms bothersome everyday; 4 = symptoms affect daily activities; and 5 = symptoms are incapacitating (unable to do daily activities). The total score was summed and reported. The maximum obtainable total score was 50 and minimum obtainable total score was 0, with higher scores indicating a worse outcome and lower scores indicating a better outcome.
Time Frame
Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Title
Safety and Tolerability
Description
Assessed by monitoring adverse events reported by patients
Time Frame
Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Title
Circulating Plasma Concentration of Gastrin
Description
The level of gastrin biomarkers circulating in the blood was measured.
Time Frame
Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Title
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate
Description
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
Volume of aspirate (mL)
Acid in aspirate (mEq)
Acid output (mEq)
Time Frame
Week 2 visit (baseline) and Week 6 visit
Title
Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output
Description
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
Volume of aspirate (mL)
Acid in aspirate (mEq)
Acid output (mEq)
Time Frame
Week 2 visit (baseline) and Week 6 visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Men; post-menopausal women; pre-menopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy; or pre-menopausal women using one of the allowed methods of contraception: condom and spermicide or intra-uterine device.
Patients with serum gastrin >250 pg/mL.
Hepatic function: AST and ALT ≤2.0 x ULN; total bilirubin ≤1.0 x ULN.
Renal function: serum creatinine <1.0 x ULN.
Haematologic function: Hb ≥10.0 g/dL; WBC ≥3.5 x 10e9 /L; ANC ≥1.5 x 10e9 /L; platelets ≥100 x 10e9 /L.
Coagulation parameters: INR or PT ≤1.0 x ULN; PTT ≤1.0 x ULN.
Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
Willingness to give fully-informed, written consent.
Exclusion criteria:
Patients under 18 years.
Women who are pregnant, lactating or using a steroid contraceptive.
Prior gastric resection or bypass.
Planned gastrinoma resection during the study period.
Patients on somatostatin analogues, except for those on therapy for >6 months with stable or worsening carcinoids.
Inability to tolerate endoscopy, or refusal of endoscopy.
Physical findings, ECG (especially prolonged QTc interval >450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
Certain medicines and herbal remedies taken during the 7 days before visit 2.
Participation in a trial of an IMP within the previous 28 days.
Presence of drug or alcohol abuse.
History or baseline findings of:
type 1 diabetes mellitus;
pancreatitis (baseline amylase and/or >2.0 x ULN);
hepatitis B, hepatitis C or HIV;
malabsorption syndrome or inability to swallow or retain oral medicine;
major surgery <28 days prior to enrolment;
ECOG performance status >2; or
another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in-situ.
Also, any clinically significant and uncontrolled major morbidity including but not limited to; serious cardiac disease (unstable angina, s/p myocardial infarction <1 month); respiratory disease (advanced COPD or pulmonary fibrosis); uncontrolled hypertension; or active systemic infection.
12. IPD Sharing Statement
Learn more about this trial
YF476 and Type II Gastric Carcinoids
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