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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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ClinicalTrials.gov Identifier: NCT02901483
Recruitment Status : Recruiting
First Posted : September 15, 2016
Last Update Posted : January 5, 2021
Sponsor:
Information provided by (Responsible Party):
PharmaEngine

Tracking Information
First Submitted Date  ICMJE August 31, 2016
First Posted Date  ICMJE September 15, 2016
Last Update Posted Date January 5, 2021
Actual Study Start Date  ICMJE October 11, 2016
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2016)
  • Phase 1: Determination of the Recommended doses and the Dose Limiting Toxicities (DLT) [ Time Frame: 24 months ]
    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 [ Time Frame: 24 months ]
    To evaluate the rate of locoregional control at one year after PEP503 intratumor injection
  • Phase1 and 2: Evaluation of Safety profile of PEP503 [ Time Frame: 24 months ]
    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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2016)
  • Phase 1: The body kinetic profile of PEP503 [ Time Frame: 24 months ]
    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) [ Time Frame: 24 months ]
    To evaluate the objective tumor rate by using RECIST v1.1 after intratumor injection schedule, activated by CCRT
  • Phase 2: Pathological response (pR) [ Time Frame: 24 months ]
    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 [ Time Frame: 24 months ]
    To evaluate the progression free survival rate at 1 year after the intratumor injection of PEP503
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of PEP503 With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer
Official Title  ICMJE A Phase 1b/2 Study of PEP503 (Radioenhancer) With Radiotherapy in Combination With Concurrent Chemotherapy for Patients With Head and Neck Cancer
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Squamous Cell Carcinoma
Intervention  ICMJE
  • Drug: PEP503
    PEP503 will be administered by intratumoral route as slow injection
    Other Name: NBTXR3
  • Drug: Cisplatin
    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.
  • Radiation: Radiotherapy
    Patients will receive 70-72 Gy, 2-2.12 Gy/fraction over 7~8 weeks.
Study Arms  ICMJE Experimental: PEP503+Cisplatin+Radiotheraphy

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.

Interventions:
  • Drug: PEP503
  • Drug: Cisplatin
  • Radiation: Radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 10, 2016)
42
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Weiche Yu +886 2 25158228 weiche.yu@pharmaengine.com
Contact: Erica Wang +886 2 25158228 ext 201 erica.wang@pharmaengine.com
Listed Location Countries  ICMJE Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02901483
Other Study ID Numbers  ICMJE PEP503-HN-1002
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PharmaEngine
Study Sponsor  ICMJE PharmaEngine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Cheng-Hsu Wang, M.D. Keelung Chang Gung Memeorial Hospital (Lovers Lake Branch)
PRS Account PharmaEngine
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP