Durvalumab With or Without Tremelimumab in Resectable Locally Advanced Squamous Cell Carcinoma of the Oral Cavity

NCT03784066 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: ESR-16-121922017-000577-36
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, prospective, pilot phase I/II study with focus on translational research and on the evaluation of the biological changes that are observed in sequential tumor tissue acquisition in patients with newly diagnosed advanced (stage IV) oral cavity SCC. Patients are treated with Durvalumab (arm A) or Durvalumab + Tremelimumab (arm B) after biopsy-confirmed diagnosis of locally advanced resectable SCCHN of the oral cavity. After surgery, the standard of care treatment is radiotherapy, and, depending on risk assessment concurrent cisplatin. Patients will be treated with Durvalumab (arm A) or Durvalumab and Tremelimumab (arm B) during six additional cycles, starting from day one of the postoperative radiotherapy.

Conditions

Oral Cavity Squamous Cell Carcinoma

Keywords

squamous cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluation of biological response in tumor tissue by means of difference in CD8 lymfocyte infiltration density

  Difference in CD8 infiltration density will be evaluated on Formalin-Fixed Paraffin-Embedded sections. Measurements will be done both visually by trained pathologists and quantitative on immunofluorescence panel.

  The first biopsy will be harvested as part of the diagnostic screening procedures between day 28 and 14 before surgery. The second biopsy will be harvest from the resection specimen on day 0. IP will be given exactly 14 days before surgery.

Secondary Outcomes (5)

• Imaging

  After 14 days of treatment, prior to surgery

• 68Ga-CXCR-4 PET/MR (optional)

  After 14 days of treatment, prior to surgery

• Locoregional control in days

  Up to 2 years after surgery

• Time to treatment failure in days

  Up to 2 years after surgery

• Overall survival in days

  Up to 5 years after surgery

Study Arms (2)

A

ACTIVE COMPARATOR

Durvalumab

Drug: Durvalumab

B

ACTIVE COMPARATOR

Durvalumab + Tremelimumab

Combination Product: Durvalumab + Tremelimumab

Interventions

Durvalumab DRUG

All patients will be treated with postoperative radiotherapy (66 Gy in standard fractionation). In case of positive section margins or extracapsular extension, 3 cycles of cisplatin 100 mg/msq on days 1, 22, and 43 will be added to standard fractionation radiotherapy (66 Gy). Durvalumab monotherapy (1500 mg) will be administered via IV infusion day -14 and at the start of radiation therapy, with repeat administration every 4 weeks at fixed dose for a total of 6 cycles postoperative.

A

Durvalumab + Tremelimumab COMBINATION_PRODUCT

All patients will be treated with postoperative radiotherapy (66 Gy in standard fractionation). In case of positive section margins or extracapsular extension, 3 cycles of cisplatin 100 mg/msq on days 1, 22, and 43 will be added to standard fractionation radiotherapy (66 Gy). Durvalumab + Tremelimumab combination therapy: Tremelimumab (75 mg) will be administered via IV infusion day -14 and at the start of radiation therapy, with repeat administration every 4 weeks at fixed dose for a total of 3 cycles postoperative, Durvalumab (1500 mg) will be administered via IV infusion day -14 and at the start of radiation therapy, with repeat administration every 4 weeks at fixed dose for a total of 6 cycles postoperative.

B

Eligibility Criteria

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

You may qualify if:

• Resectable locally advanced oral cavity SCC stage IV
• Newly diagnosed disease
• Age ≥18 years at the time of screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
• No active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix
• No prior chemotherapy, radiotherapy or targeted therapy including PD-1, PD-L1 or CTLA-4 antibodies for SCCHN, including durvalumab or tremelimumab
• Availability of blood samples for Translational research
• Negative pregnancy test
• Normal organ function
• No participation in another interventional clinical trial in the preceding 30 days prior to randomization
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations
• Body weight \> 30 kg

You may not qualify if:

• Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck
• Receipt of other treatments for cancer within 30 days prior to first dose of study treatment
• Previous radiotherapy in the head and neck region
• Previous systemic therapy for SCCHN
• Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP.
• History of allogeneic organ transplantation
• Active or prior documented autoimmune or inflammatory
• Uncontrolled intercurrent illness
• Active relevant second malignancy during the last five years
• Mean QT interval corrected for heart rate ≥470 ms
• History of active primary immunodeficiency
• Active infection Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
• Female patients of childbearing potential who are pregnant or breast-
• Known allergy or hypersensitivity to IP or any IP excipient
• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• AstraZeneca: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• Vlaams Instituut voor Biotechnologie (VIB): collaborator

Study Sites (1)

UZ Leuven

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Paul Clement, Prof.

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The primary objective is to evaluate the biological response in the tumor upon treatment with Durvalumab, and in parallel, with combination of Durvalumab and Tremelimumab.

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: December 21, 2018
• Study Start: August 27, 2018
• Primary Completion: March 24, 2025
• Study Completion: March 24, 2026
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)