This is a study of MEDI4736 monotherapy in patients with head and neck cancer, who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.

• Register: EUCTR
• Last refreshed on: 31 August 2020
• Main ID: EUCTR2014-003295-23-HU
• Date of registration: 02/02/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: This is a study of MEDI4736 monotherapy in patients with head and neck cancer, who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.
• Scientific title: A Phase II, Multi-Center, Single-Arm, Global Study of MEDI4736 Monotherapy in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN).
• Date of first enrolment: 02/02/2015
• Target sample size: 112
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003295-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, France, Georgia, Germany, Hungary, Israel, Korea, Republic of, Malaysia, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca

• Name: Clinical Trial Transparency
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age =18 years at the time of screening
2. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
3. Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Patients who refuse radical resection are eligible.
4. Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease the must have contained a platinum agent. Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible.
5. Able and willing to give valid written consent to provide newly acquired tumor tissue (preferred) or archival tissue (<3 years old) for the purpose of establishing PD-L1 status. Tumor lesions used for newly acquired biopsies should not be the same lesions used as RECIST 1.1 target lesions, unless there are no other lesions suitable for biopsy.
6. Confirmed PD-L1–positive SCCHN by the Ventana SP263 assay on newly acquired tumor tissue (preferred) or archival tissue (<3 years old). If the patient's PD-L1 status has already been assessed using the analytically validated Ventana assay as a part of the screening process for another AstraZeneca/MedImmune study, this test result can be used for the determination of eligibility provided no intervening therapy has been administered.
7. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment.
8. At least 1 lesion, not previously irradiated, that can be accurately measured at baseline as =10 mm in the longest diameter (except lymph nodes which must have a short axis =15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. Lesions in a previously irradiated field can be used as measurable disease provided that there has been demonstrated progression in the lesion.
9. Patients must have no prior exposure to immune-mediated therapy, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines. Prior exposure to other investigational agents may be permitted after discussion with the sponsor.
10. Adequate organ and marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening, defined as:
- Hemoglobin =9 g/dL
- Absolute neutrophil count =1500/mm3
- Platelet count =100000/mm3
- Serum bilirubin =1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician.
- ALT and AST =2.5 × ULN; for patients with hepatic metastases, ALT and AST =5 × ULN
- Calculated creatinine clearance =40 mL/min as determined by Cockcroft-Gault (using actual body weight)
11. 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 f
Exclusion criteria:
1.Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck, patients with squamous cell carcinoma of the head and neck of unknown primary, and non-squamous histologies (eg, nasopharynx or salivary gland)
2.Received more than 1 systemic palliative regimen for recurrent or metastatic disease
3.Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (eg, local surgery or radiotherapy)
4.Prior randomization or treatment in a previous MEDI4736 and/or tremelimumab clinical study regardless of treatment arm assignment or receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment
5.Receipt of last dose of an approved (marketed) anticancer therapy within 21 days prior to the first dose of study treatment. If sufficient washout time has not occurred due to the schedule or PK properties of an agent, a longer washout period will be required, as agreed upon by AstraZeneca and 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.Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion *Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with MEDI4736 (eg, hearing loss) may be included after consultation with the Study Physician
8.Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent- Steroids as pre-medication for hypersensitivity reactions
9.History of allogeneic organ transplantation
10.Active or prior documented autoimmune or inflammatory disorders (eg, inflammatory bowel disease [eg, colitis, Crohn’s disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: *Patients with vitiligo or alopecia *Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or other chronic skin conditions not requiring systemic treatment
11.Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness or social situations that would limit compliance with study requirements, substantially increase the risk of incurring AEs from MEDI4736 , or compromise the ability of the

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Recurrent or metastatic PD-L1-positive squamous cell carcinoma of the head and neck (SCCHN).
MedDRA version: 20.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not applicable
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other descriptive name: MEDI4736
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: To further assess the efficacy of MEDI4736 monotherapy in terms of objective response rate (ORR), duration of response (DoR), disease control rate (DCR), deep sustained response (DSR), progression-free survival (PFS), and overall survival (OS).
To explore symptoms and health-related quality of life (QoL) in patients treated with MEDI4736 monotherapy using the EORTC 30-item core quality of life questionnaire, version 3 (QLQ-C30 v3) and the 35-item head and neck quality of life questionnaire (QLQ-H&N35) module.
To assess the safety and tolerability profile of MEDI4736 monotherapy

Primary end point(s): The primary endpoint is the objective response rate (ORR). ORR is defined as the number (%) of patients with a confirmed overall response of complete response (CR) or partial response (PR) and will be based on all treated patients who have measurable disease at baseline per BICR.

Timepoint(s) of evaluation of this end point: A confirmed response of confirmed or partial response means that a response of complete or partial response is recorded at one visit and confirmed by repeat imaging not less than 4 weeks after the visit when the response was first observed with no evidence of progression between the initial and confirmed or partial response confirmation visit. Therefore, data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of objective response rate.

Main Objective: To assess the efficacy of MEDI4736 monotherapy in terms of objective response rate (ORR).

Secondary Outcome(s)

Secondary end point(s): 1. Duration of response (DoR) - time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
2. Disease control rate (DCR) - percentage of patients who have a best objective response (BoR) of confirmed or partial response in the first 4 or 12 months or who have demonstrated stable disease (SD) for a minimum interval of 16 or 52 weeks following the start of treatment.
3. Progression-free survival (PFS) - time from the date of first dose until the date of objective disease progression or death.
4. Overall survival (OS) - time from the date of enrollment until death due to any cause.
5. Best objective response (BoR) - the best response a patient has had during their time in the
study up until RECIST or confirmed progression or the last evaluable assessment.

Timepoint(s) of evaluation of this end point: 1. DoR - time of the initial response will be defined as the latest of the dates contributing towards the first visit response of PR or CR.
2. DCR - first 4 or first 12 months.
3. PFS time will be derived based on scan/assessment dates.
4. OS - The DCO for the final analysis of OS will take place approximately 30 months after LPD (last patient dosed).
5. BoR - for deaths occuring =17 weeks after enrollment BoR will be assigned to the progressive disease (PD) category and for deaths occuring >17 weeks after enrollment BoR will be assigned to the not evaluable (NE) category.

Secondary ID(s)

D4193C00001

2014-003295-23-GB

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 15/12/2014
Contact: