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

NCT02901483 | Terminated Phase 1

• 1 other identifier: PEP503-HN-1002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Head and Neck

Outcome Measures

Primary Outcomes (3)

• 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

  24 months

• Phase 2: The rate of locoregional control at one year

  To evaluate the rate of locoregional control at one year after PEP503 intratumor injection

  24 months

• 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

  24 months

Secondary Outcomes (4)

• Phase 1: The body kinetic profile of PEP503

  24 months

• Phase 2: Evaluation of objective tumor response as per Response Evaluation Criteria in Solid Tumors (RECIST)

  24 months

• Phase 2: Pathological response (pR)

  24 months

• Phase 2: Evalution of progression free survival rate at 1 year

  24 months

Study Arms (1)

PEP503+Cisplatin+Radiotheraphy

EXPERIMENTAL

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.

Drug: PEP503; Drug: Cisplatin; Radiation: Radiotherapy

Interventions

PEP503 DRUG

PEP503 will be administered by intratumoral route as slow injection

Also known as: NBTXR3

PEP503+Cisplatin+Radiotheraphy

Cisplatin DRUG

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.

PEP503+Cisplatin+Radiotheraphy

Radiotherapy RADIATION

Patients will receive 70-72 Gy, 2-2.12 Gy/fraction over 7\~8 weeks.

PEP503+Cisplatin+Radiotheraphy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PharmaEngine: lead

Study Sites (1)

Keelung Chang Gung Memorial Hospital (Lovers Lake Branch)

Keelung, Taiwan

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Cheng-Hsu Wang, M.D.

  Keelung Chang Gung Memeorial Hospital (Lovers Lake Branch)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2016
• First Posted: September 15, 2016
• Study Start: October 11, 2016
• Primary Completion: August 17, 2020
• Study Completion: August 17, 2020
• Last Updated: January 11, 2022

Record last verified: 2021-12

Locations

TW (1)