Trial evaluating the tolerance and safety of durvalumab - radiotherapy combination for treatment of cancers of the head and neck

Phase 1

• Conditions: ntreated Squamous cell carcinoma : Oral cavity, oropharynx, hypopharynx or larynx; MedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001976-39-FR
• Lead Sponsor: GORTEC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-10-22
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

1.Age > 18 years with no upper limit
2.Performance Status ECOG 0-2
3.Non-eligible to existing SOC with chemo-RT or cetuximab-RT
4.Squamous cell carcinoma, previously untreated
5.T1-T2 N0 with measurable disease for whom the risk of nodal spread is estimated to be low (< 10-15%) or T3-T4 N0 with measurable disease for whom large field neck irradiation may not be appropriate due to age, and/or fragile condition (PS2)
6.N0 neck based on clinical, MRI and FDG/PET-CT examinations
7.Oral cavity, oropharynx, hypopharynx or larynx
8.Availability of pre-treatment tumor tissue sample (for PD-L1 expression, TILs and immune landscape)
9.Documentation of p16 disease (HPV status for oropharyngeal tumor)
10.Recording of alcohol consumption and smoking history
11.Adequate normal organ and marrow function as defined below:
- Haemoglobin > 9.0 g/dL
- Absolute neutrophil count (ANC) = 1500 per mm3
- Platelet count > 100 000 per mm3
- Serum bilirubin < 1.5 x institutional upper limit of normal (ULN)
- AST (SGOT)/ALT (SGPT) = 2.5 x institutional ULN
12.Measured creatinine clearance (CL) >40 mL/min (CKD-EPI method recommended) or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula
13.Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations during the follow up period
14.Patient able to understand French and complete the quality of life questionnaires
15.Must have a life expectancy of at least 12 weeks
16.Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
17.Patient capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1.Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
2.Metastatic disease
3.Active CNS disease
4.Any prior or current treatment for invasive head and neck cancer
5.Any unresolved toxicity NCI CTCAE V5.0 Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
a. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis
b. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the investigator
6.Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable
7.History of leptomeningeal carcinomatosis
8.Body weight = 30 kg and/or weight loss of = 15% during the last 4 weeks (except if re-nutrition with a feeding tube is planned before the onset of treatment or is ongoing)
9.Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
10.Concomitant treatment with any drug on the prohibited medication list such as live vaccines within 30 days prior to the first dose of IP
11.Known allergy or hypersensitivity reaction to study drug or any of the study drug excipients
12.Prior organ transplantation including allogenic stem-cell transplantation
13.Other severe acute or chronic medical conditions including pneumonitis, pulmonary fibrosis
14.Active autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc])
15.Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
16.History of another primary malignancy except for:
a.Malignancy treated with curative intent and with no known active disease = 5 years
b.Adequately treated non-melanoma skin cancer
c.Adequately treated carcinoma in situ without evidence of disease
17.History of active primary immunodeficiency
18. Ongoing or active infection including tuberculosis, hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
19.Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
a.Intranasal, inhaled, topical steroids, or local steroid injections
b.Systemic corticosteroids < 10 mg/day of prednisone or its equivalent
c.Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified