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A Study of PEP503 With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer

Primary Purpose

Head and Neck Squamous Cell Carcinoma

Status
Terminated
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
PEP503
Cisplatin
Radiotherapy
Sponsored by
PharmaEngine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Squamous Cell Carcinoma focused on measuring Head and Neck

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed squamous cell carcinoma (SCC) of oral cavity, oropharynx, hypopharynx, or larynx
  • Locally advanced or recurrent disease of: Oral Cavity:T4b, N any, who are not candidates for surgical resection; or T3-4, N any, who decline surgery or medical inoperable; OR Oropharynx, hypopharynx, or larynx: T3-4, N any
  • No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan
  • ECOG Performance Status 0 or 1

  • Adequate function of bone marrow, kidney and liver:

    • White Blood Cell (WBC) ≥ 3.0 x 109/l
    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/l
    • Platelet count ≥ 100 x 109/l
    • Hemoglobin ≥ 9.0 g/dL
    • Creatinine within normal range, for dose level with tri-weekly cisplatin, estimated GFR ≥ 60 mL/min/1.73m2 or CrCl ≥ mL/min is also required
    • AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN and Alkaline phosphatase (ALP) ≤ 2.5 x ULN
    • Bilirubin ≤ 1.5 x ULN
  • 20 years of age or older
  • All female patients of childbearing potential must have negative urine pregnancy test within 7 days prior to study treatment with PEP503. Fertile patients must agree to use effective contraception during the study

Exclusion Criteria:

  • Tumor ulceration combined with vascular risks
  • Prior radiotherapy to any area within the planned radiotherapy field
  • Uncontrolled intercurrent illness
  • Concurrent treatment with any other anticancer therapy
  • Participation in any investigational drug study within 4 weeks
  • Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer, and any other cancer from which the subject has been cancer free for 5 years
  • Patients unable to comply with scheduled visits and other study procedures.
  • Preexisting neuropathy ≥ Grade 2 (CTCAE)
  • Pre-existing hearing impairment > Grade 2 (CTCAE) for patients receiving cisplatin 100 mg/m2
  • History of allergic reaction to platinum product

Sites / Locations

  • Keelung Chang Gung Memorial Hospital (Lovers Lake Branch)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PEP503+Cisplatin+Radiotheraphy

Arm Description

Phase 1b: There are 6 levels (L1- 5% + 40mg/m2 weekly cisplatin, L2- 10% + 40mg/m2 weekly cisplatin, L3- 15% + 40mg/m2 weekly cisplatin, L4-22% + 100mg/m2 tri-weekly cisplatin, L3a- 15% + 100mg/m2 tri-weekly cisplatin, and L5- 33% + 100mg/m2 tri-weekly cisplatin) in this phase 1b study. Only primary tumor will receive PEP503 implementation via intratumor injection. A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503. Phase 2: The recommended volume identified from phase 1b will be applied in phase 2 for both primary tumor and ≥ 3 cm lymph node lesions.

Outcomes

Primary Outcome Measures

Phase 1: Determination of the Recommended doses and the Dose Limiting Toxicities (DLT)
To determine the Recommended volumes and the Dose Limiting Toxicities (DLT) of PEP503 administered as intratumor injection, activated by CCRT
Phase 2: The rate of locoregional control at one year
To evaluate the rate of locoregional control at one year after PEP503 intratumor injection
Phase1 and 2: Evaluation of Safety profile of PEP503
Safety of PEP503, as intratumor injection schedule, activated by CCRT will be assessed in terms of incidence and severity of clinical and laboratory Adverse Events by NCI-CTCAE version 4.0

Secondary Outcome Measures

Phase 1: The body kinetic profile of PEP503
To characterize the body kinetics on Date of injection(DINJ) of PEP503 administered by intratumor injection before CCRT
Phase 2: Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST)
To evaluate the objective tumor rate by using RECIST v1.1 after intratumor injection schedule, activated by CCRT
Phase 2: Pathological response (pR)
If patients receive tumor and/or neck lymph node dissection after treatment, to assess according to the evidence of viable tumor cell
Phase 2: Evalution of progression free survival rate at 1 year
To evaluate the progression free survival rate at 1 year after the intratumor injection of PEP503

Full Information

First Posted
August 31, 2016
Last Updated
December 17, 2021
Sponsor
PharmaEngine
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1. Study Identification

Unique Protocol Identification Number
NCT02901483
Brief Title
A Study of PEP503 With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer
Official Title
A Phase 1b/2 Study of PEP503 (Radioenhancer) With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
bussiness reason
Study Start Date
October 11, 2016 (Actual)
Primary Completion Date
August 17, 2020 (Actual)
Study Completion Date
August 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PharmaEngine

4. Oversight

5. Study Description

Brief Summary
It's a prospective, open-label, single arm, nonrandomized study of PEP503 in head and neck squamous cell carcinoma (HNSCC) patients. Escalation portion (Phase 1b):A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503. Expansion portion (Phase 2): Following confirmation of the recommended volumes, 18 additional patients will be enrolled at the recommended volume level to evaluate for safety and efficacy.
Detailed Description
Primary Objectives: Phase 1b (dose escalation portion): To assess the safety profile and determine the Dose Limiting Toxicity (DLT) and to define the recommended volumes (doses) of PEP503. Phase 2 (expansion portion): To evaluate the anti-tumor activity in terms of the rate of locoregional control at one year and to evaluate the safety profile. Secondary Objectives: Phase 1b: To characterize the body kinetic profile of PEP503. Phase 2: Objective tumor response, progression free survival rate at 1 year and pathological response (pR). The target population is composed by patients who have pathologically confirmed squamous cell carcinoma of oral cavity with disease clinically staged as T4b who are not candidates for surgical resection or T3-4 who decline surgery or medical inoperable, or oropharynx, hypopharynx, or larynx with disease clinical staged as T3-4, without metastasis disease. ECOG performance status 0 or 1 and adequate bone marrow, renal, and hepatic function. Dose limiting toxicity (DLT) - The DLTs are related to PEP503, injection procedure, or concurrent chemo radiation therapy and occur in the DLT evaluation period. The DLT evaluation period starts from the intratumor injection of PEP503 to 4 weeks after the completion of radiation treatment. There are 6 levels (Level 1, Level 2, Level 3, Level 4, Level 3a and Level 5) in this phase 1b study. PEP503 will be given at the fixed concentration of 53.3g/L. The starting volume of PEP503 to be injected is 5% (Level 1) of the tumor volume confirmed by MRI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Squamous Cell Carcinoma
Keywords
Head and Neck

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PEP503+Cisplatin+Radiotheraphy
Arm Type
Experimental
Arm Description
Phase 1b: There are 6 levels (L1- 5% + 40mg/m2 weekly cisplatin, L2- 10% + 40mg/m2 weekly cisplatin, L3- 15% + 40mg/m2 weekly cisplatin, L4-22% + 100mg/m2 tri-weekly cisplatin, L3a- 15% + 100mg/m2 tri-weekly cisplatin, and L5- 33% + 100mg/m2 tri-weekly cisplatin) in this phase 1b study. Only primary tumor will receive PEP503 implementation via intratumor injection. A 3 + 3 dose escalation study design will be adopted in this phase to identify the recommended intratumor injection volumes of PEP503. Phase 2: The recommended volume identified from phase 1b will be applied in phase 2 for both primary tumor and ≥ 3 cm lymph node lesions.
Intervention Type
Drug
Intervention Name(s)
PEP503
Other Intervention Name(s)
NBTXR3
Intervention Description
PEP503 will be administered by intratumoral route as slow injection
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
The concurrent chemoradiotherapy. Weekly cisplatin 40 mg/m2 or tri-weekly 100 mg/m2, depending on which dose level patients are in, with a minimum of accumulated 200 mg/m2 during the 7~8 weeks' radiation period.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Patients will receive 70-72 Gy, 2-2.12 Gy/fraction over 7~8 weeks.
Primary Outcome Measure Information:
Title
Phase 1: Determination of the Recommended doses and the Dose Limiting Toxicities (DLT)
Description
To determine the Recommended volumes and the Dose Limiting Toxicities (DLT) of PEP503 administered as intratumor injection, activated by CCRT
Time Frame
24 months
Title
Phase 2: The rate of locoregional control at one year
Description
To evaluate the rate of locoregional control at one year after PEP503 intratumor injection
Time Frame
24 months
Title
Phase1 and 2: Evaluation of Safety profile of PEP503
Description
Safety of PEP503, as intratumor injection schedule, activated by CCRT will be assessed in terms of incidence and severity of clinical and laboratory Adverse Events by NCI-CTCAE version 4.0
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Phase 1: The body kinetic profile of PEP503
Description
To characterize the body kinetics on Date of injection(DINJ) of PEP503 administered by intratumor injection before CCRT
Time Frame
24 months
Title
Phase 2: Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST)
Description
To evaluate the objective tumor rate by using RECIST v1.1 after intratumor injection schedule, activated by CCRT
Time Frame
24 months
Title
Phase 2: Pathological response (pR)
Description
If patients receive tumor and/or neck lymph node dissection after treatment, to assess according to the evidence of viable tumor cell
Time Frame
24 months
Title
Phase 2: Evalution of progression free survival rate at 1 year
Description
To evaluate the progression free survival rate at 1 year after the intratumor injection of PEP503
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma (SCC) of oral cavity, oropharynx, hypopharynx, or larynx Locally advanced or recurrent disease of: Oral Cavity:T4b, N any, who are not candidates for surgical resection; or T3-4, N any, who decline surgery or medical inoperable; OR Oropharynx, hypopharynx, or larynx: T3-4, N any No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan ECOG Performance Status 0 or 1 Adequate function of bone marrow, kidney and liver: White Blood Cell (WBC) ≥ 3.0 x 109/l Absolute neutrophil count (ANC) ≥ 1.5 x 109/l Platelet count ≥ 100 x 109/l Hemoglobin ≥ 9.0 g/dL Creatinine within normal range, for dose level with tri-weekly cisplatin, estimated GFR ≥ 60 mL/min/1.73m2 or CrCl ≥ mL/min is also required AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN and Alkaline phosphatase (ALP) ≤ 2.5 x ULN Bilirubin ≤ 1.5 x ULN 20 years of age or older All female patients of childbearing potential must have negative urine pregnancy test within 7 days prior to study treatment with PEP503. Fertile patients must agree to use effective contraception during the study Exclusion Criteria: Tumor ulceration combined with vascular risks Prior radiotherapy to any area within the planned radiotherapy field Uncontrolled intercurrent illness Concurrent treatment with any other anticancer therapy Participation in any investigational drug study within 4 weeks Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer, and any other cancer from which the subject has been cancer free for 5 years Patients unable to comply with scheduled visits and other study procedures. Preexisting neuropathy ≥ Grade 2 (CTCAE) Pre-existing hearing impairment > Grade 2 (CTCAE) for patients receiving cisplatin 100 mg/m2 History of allergic reaction to platinum product
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cheng-Hsu Wang, M.D.
Organizational Affiliation
Keelung Chang Gung Memeorial Hospital (Lovers Lake Branch)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Keelung Chang Gung Memorial Hospital (Lovers Lake Branch)
City
Keelung
Country
Taiwan

12. IPD Sharing Statement

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A Study of PEP503 With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer

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