HPPH Photodynamic Therapy for Patients With Esophageal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Esophageal Cancer

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Multiple Ascending Dose, Multiple groups, Multiple centers
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPPH 2.5 mg/m2<br>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<br>* 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.<br>|
| Experimental: HPPH 3 mg/m2<br>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<br>* 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.<br>|
| Experimental: HPPH 3.5 mg/m2<br>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<br>* 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.<br>|
| Experimental: HPPH 4 mg/m2<br>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<br>* 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.<br>|
| Experimental: HPPH 5 mg/m2<br>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<br>* 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.<br>|
| Experimental: HPPH 6 mg/m2<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PHHP, Esophageal cancer, Phase I study