HPPH Photodynamic Therapy for Patients With Esophageal Cancer (HPPH)

Evalution of Safety, Tolerability and Pharmacokinetics of of HPPH in Ascending Dose for Cancer Patients in Phase I Clinical Trial

Phase I study was to investigate the safety and tolerability of the photosensitizer (PS) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) for injection in patients with Esophageal Cancer. It was to characterize the pharmacokinetics of HPPH and efficacy of HPPH.

Study Overview

• Status: Unknown
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: HPPH 2.5 mg/m2; Drug: HPPH 3 mg/m2; Drug: HPPH 3.5 mg/m2; Drug: HPPH 4 mg/m2; Drug: HPPH 5 mg/m2; Drug: HPPH 6 mg/m2

Detailed Description

The present study is phase I study to evaluate the safety, tolerability, and pharmacokinetics of multiple ascending injection doses of HPPH in Patients with Esophageal Cancer. Up to 30 patients are planned to be enrolled in 6 cohorts with each cohort consisting of 3-6 patients ( male and/or female patients). In each cohort, patients will receive HPPH and Lyophilized treatment. The dose escalation in Cohorts was from 2.5 to 3, 3.5, 4, 5, and 6mg/m2 of HPPH, respectively, administered intravenous drop infusion over 1 hour, once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Department of Oncology, General Hospital of Beijing Miitary Command of PLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or older, Male and female subjects with practicing a highly effective form of birth control, and a signed consent;
• Subjects who was diagnosed as Esophageal Cancer or carcinoma of gastric cardia by endoscopy and Biopsy pathology at T1-T3 stage.
• Subjects who could not be taken surgery or chemotherapy; with unsucessful surgery or failed chemotherapy; who had refused surgery and chemotherapy
• ECOG 0-2, Life expectancy would be more than 3-month

Exclusion Criteria:

• Subjects were diagnosed as Tracheoesophageal fistula or Esophageal mediatinal fistula, or more than 60 years old with having three kinds of Heart, Lung, Liver and Kidney commorbities;
• Hematopoietic WBC < 3×109/L; HGB <80g/L; PLT <80×109/L; PLT <1.5 times upper limit of normal (ULN)
• Hepatic TBIL>1.5ULN, ALT or AST >2.5 ULN
• Alkaline phosphatase > 3 times ULN
• Uncontrol Hypertension: Bp>160/100mmHg
• Uncomtrol Diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HPPH 2.5 mg/m2; HPPH 2.5 mg/m2, Freeze-dried powder injection, intravenous infusion once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.	Drug: HPPH 2.5 mg/m2; HPPH was administered as a single, 2.5 mg/m2, slow intravenous infusion over 1 hour , and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.
Experimental: HPPH 3 mg/m2; HPPH 3 mg/m2, Freeze-dried powder injection, intravenous infusion once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.	Drug: HPPH 3 mg/m2; HPPH was administered as a single, 3 mg/m2, slow intravenous infusion over 1 hour, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.
Experimental: HPPH 3.5 mg/m2; HPPH 3.5 mg/m2, Freeze-dried powder injection, intravenous infusion once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.	Drug: HPPH 3.5 mg/m2; HPPH was administered as a single, 3.5 mg/m2, slow intravenous infusion over 1 hour, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.
Experimental: HPPH 4 mg/m2; HPPH 4 mg/m2, Freeze-dried powder injection, intravenous infusion once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.	Drug: HPPH 4 mg/m2; HPPH was administered as a single, 4 mg/m2, slow intravenous infusion over 1 hour, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.
Experimental: HPPH 5 mg/m2; HPPH 5 mg/m2, Freeze-dried powder injection, intravenous infusion once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.	Drug: HPPH 5 mg/m2; HPPH was administered as a single, 5 mg/m2, slow intravenous infusion over 1 hour, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.
Experimental: HPPH 6 mg/m2; HPPH 6 mg/m2, Freeze-dried powder injection, intravenous infusion once daily, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.	Drug: HPPH 6 mg/m2; HPPH was administered as a single, 6 mg/m2, slow intravenous infusion over 1 hour, and a fixed light dose of 150 J/cm delivered 48 hours after infusion of HPPH.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of dose-limiting toxicity	Dose-limiting toxicity would be assesed by CTCAE4.0	Day 1 to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (Cmax)	PK measurement expressed as Cmax for HPPH	Day 1 to Day 84
Time to maximum concentration (tmax)	PK measurement expressed as Tmax for HPPH	Day 1 to Day 84
Apparent terminal elimination phase half (t1/2)	PK measurement expressed as t1/2 for HPPH	Day 1 to Day 84
Area under the concentration-time curve over the dosing interval (AUC0-t)	PK measurement expressed as AUC0-t for HPPH	Day 1 to Day 84
Area under the concentration-time curve from zero extrapolated to infinity (AUC0-∞)	PK measurement expressed as AUC0-∞ for HPPH	Day 1 to Day 84

Collaborators and Investigators

• Sponsor: Zhejiang Hisun Pharmaceutical Co. Ltd.
• Investigators: Principal Investigator: Huilong Liu, PhD, General Hospital of Beijing Miitary Command of PLA

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2015
• Primary Completion (Anticipated): January 20, 2019
• Study Completion (Anticipated): May 27, 2019

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2018
• Last Update Submitted That Met QC Criteria: November 27, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Phase I study; Esophageal cancer; PHHP
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: HISUN-HPPH-I-2014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No