Feasibility & Efficacy of Durvalumab+Tremelimumab+RT and Durvalumab+RT in Non-resect. Locally Advanced HPVnegativ HNSCC

NCT03624231 | Completed Phase 2 DMC

• 1 other identifier: DURTRE-RAD
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

Phase II trial evaluating to assess the feasibility and efficacy as first-line therapy for patients with non-resectable locally advanced HPV negative HNSCC of Durvalumab a PDL1-Inhibitor plus Tremelimumab a CTLA-4- Inhibitor in combination with radiotherapy and Durvalumab in combination with radiotherapy as first-line therapy. 2-arm, randomized, multicenter, phase II. Step 1 is Registration. All patients need to sign the informed consent form for registration. Tumor tissue then be send to the central lab for defining the HPV status. If the patient is HPV negative the site will be notified if they can further proceed to patient randomization. Step 2 is Randomization of all eligible patients with a centrally diagnosed, HPV negative tumor in one of the two arms (Durvalumab plus Tremelimumab + radiotherapy; Durvalumab + radiotherapy) after signing the informed consent form for step 2.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (2)

• Efficacy- 1-year progression free survival (PFS)

  1-year progression free survival (PFS) depicted as the 1-year in-field-progression-free survival and 1-year distant metastasis free survival

  1 year

• Feasibility - Number of treatment discontinuations due to toxicity

  number of treatment discontinuations due to toxicity

  During treatment

Secondary Outcomes (4)

• Overall Survival (OS)

  From date of randomization until the date of death, assessed up to 3 years

• Safety - Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  From date of randomization until the date of study assessed up to 3 years

• Chronic toxicity -Number of participants with treatment-related adverse Events Lasting longer than 3 months as assessed by CTCAE v4.03 and/or RTOG/EORTC Late Radiation Morbidity Scoring Schema

  From date of randomization until the date of study assessed up to 3 years

• Quality of life (QoL) - measured by EORTC QLQ-H&N35 and EORTC QLQ-C30)

  From date of randomization until the date of study assessed up to 3 years

Study Arms (2)

Arm 1 - stopped after interims analyses

EXPERIMENTAL

Patients in arm 1 will receive a single dose of durvalumab of 1500 mg administered on day 1, 14 days prior to initiation of the radiotherapy. Radiotherapy with 35 fractions over 7 weeks (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) will start on day 14. On week 5, 9, 13 and 17 patients will receive durvalumab (1500 mg) and tremelimumab (75 mg) for up to 4 doses/cycles and then continue 1500 mg durvalumab q4w starting on week 21 to complete a total of 12 months of therapy (overall 9 single doses durvalumab including the initial dose on day 1).

Drug: Durvalumab; Drug: Tremelimumab; Radiation: Radiotherapy

Arm 2

EXPERIMENTAL

Patients in arm 2 will receive durvalumab (1500 mg) q4w starting on day 1. Radiotherapy with 35 fractions over 7 weeks (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks) will start on day 14. Overall patients will receive treatment with durvalumab mono up to a total of 12 months (up to 13 doses in total).

Drug: Durvalumab; Radiation: Radiotherapy

Interventions

Durvalumab DRUG

Durvalumab (1500 mg) starting on week 1 to complete a total of 12 months

Also known as: MEDI4736

Arm 1 - stopped after interims analyses; Arm 2

Tremelimumab DRUG

Tremelimumab (75 mg) for up to 4 doses/cycles

Arm 1 - stopped after interims analyses

Radiotherapy RADIATION

Radiotherapy with 35 fractions (administered as daily fractions of 2 Gy given 5 days every week for 7 weeks)

Arm 1 - stopped after interims analyses; Arm 2

Eligibility Criteria

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

You may qualify if:

• Patients with locally advanced histopathologically confirmed HNSCC not candidate for primary surgical treatment
• No distant metastasis (M0)
• Tumor tissue available for central testing Patient with HPV/p16 negative disease (≤70% positively stained cells) as determined by central testing
• Adequate normal organ and marrow function
• Measurable tumor according to RECIST
• Patients must be expected to complete the treatment.
• Age \> 18 years at time of study entry
• Female patients must either be of non-reproductive potential or must have a negative serum pregnancy test upon study entry and be willing to use adequate contraceptive measurements as described in the protocol
• Non-sterilized males who are sexually active with a female partner of childbearing potential must be willing to use adequate contraceptive measurements as described in the protocol section 6.5.4

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 3 months
• Prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumor reductive surgery, neo-adjuvant chemotherapy, EGFR inhibitors or radiotherapy).
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone History of primary immunodeficiency
• History of allogeneic organ transplant
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• History of hypersensitivity to durvalumab and/or tremelimumab or any excipient

Sponsors & Collaborators

• Ulrich Keilholz: lead
• Charite University, Berlin, Germany: collaborator
• AstraZeneca: collaborator

Study Sites (3)

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Vivantes Klinikum Neukölln

Berlin, 12351, Germany

Location

Charité Comprehensive Cancer Center

Berlin, 13187, Germany

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

durvalumab; tremelimumab; 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)

Therapeutics

Study Officials

• Ulrich Keilholz, MD

  Charité Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of the Charité Comprehensive Cancer Center, Principal Investigator, Clinical Professor

Model Details: 2-arm, randomized, multicenter, phase II. Step 1 is Registration. All patients need to sign the informed consent form for registration. Tumor tissue then be send to the central lab for defining the HPV status. If the patient is HPV negative the site will be notified if they can further proceed to patient randomization. Step 2 is Randomization of all eligible patients with a centrally diagnosed, HPV negative tumor one of the two arms Durvalumab plus Tremelimumab + radiotherapy; Durvalumab + radiotherapy) after signing the informed consent form for step 2.

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: August 10, 2018
• Study Start: August 15, 2018
• Primary Completion: August 17, 2023
• Study Completion: August 17, 2023
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)