Study of MEDI4736 monotherapy and MEDI4736 in combination with Tremelimumab versus Standard of Care Therapy in patients with SCCHN

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2014-003863-40-ES
• Date of registration: 31/07/2015
• Prospective Registration: No
• Primary sponsor: AstraZeneca AB
• Public title: Study of MEDI4736 monotherapy and MEDI4736 in combination with Tremelimumab versus Standard of Care Therapy in patients with SCCHN
• Scientific title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination with Tremelimumab Versus Standard of Care Therapy in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Date of first enrolment: 24/07/2015
• Target sample size: 720
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003863-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Croatia, Czech Republic, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Peru, Poland, Romania, Russian Federation, Spain, 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 (eg, Health
Insurance Portability and Accountability Act in the United States, 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. (For patients aged <20 years and enrolling in Japan, a
written informed consent should be obtained from the patient and his or her legally acceptable representative.)
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 1 regimen for recurrent or metastatic disease that must have contained platinum OR progression within 6 months from multimodality therapy containing platinum (for either locally advanced disease or recurrent/metastatic disease).
5. Able and willing to give valid written consent to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial or to provide an available archival tumor sample taken less than 3 months ago if a fresh tumor biopsy is not feasible with an acceptable clinical risk. Tumor lesions used for fresh biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy.
6. Confirmed PD-L1-positive or -negative SCCHN by a specified IHC assay on a
recent sample (<3 months) or fresh tumor biopsy
- Regardless of the age of the test result, if the patient?s PD-L1 status has
already been assessed using the 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.
- Note: A positive PD-L1 sample is measured using a defined cut-off based on
?25% of tumor cells with membrane staining of any intensity for PD-L1. A
negative PD-L1 sample is determined by 0% to 24% of tumor cells with
membrane staining for PD-L1.
7. 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 anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, excluding
therapeutic anticancer vaccines. 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 ULN. This will not apply to patients with
confirmed Gilbert?s syndrome (persistent or recurrent hyperbilirubinemia
[predominantly unconjugated bilirub
Exclusion criteria:
1.Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck not specified in the inclusion criteria, patients with SCCHN of unknown primary, and non-squamous histologies. 2.Received more than 1 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 is acceptable.
4.Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment. Receipt of last dose of an approved 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, . 5.Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. 6.Any unresolved toxicity NCI CTCAE Grade?2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia and the laboratory values defined in the inclusion criterion (i) Patients with Grade?2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Physician. (ii) Patients with a toxicity not reasonably expected to be exacerbated by treatment with their assigned IP may be included after consultation with the Physician. 7.Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP. Exceptions to this criterion:
(i) Intranasal, inhaled, topical steroids, or local steroid injections (ii)Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent (iii) Steroids as pre-medication for hypersensitivity reactions 8.History of allogeneic organ transplantation 9.Active or prior documented autoimmune or inflammatory disorders (including colitis, Crohn´s disease, diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, or other serious GI chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia gravis; Graves´ disease; rheumatoid arthritis; hypophysitis; uveitis, etc) within the past 3 years prior to the start of treatment. Exceptions to this criterion:
(i) Patients with vitiligo or alopecia; (ii) Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
10. 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 IP, or compromise the ability of the patient to give written informed consent 11.History of another primary malignancy except for
(i) Malignancy treated with curative intent and with no known active disease?5 years before the first dose of study drug and of low potential risk for recurrence (ii) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease (iii) Adequately treated carcinoma in situ without evidence of disease e.g. cervical cancer in situ. 12. Patients with history of brain metastases,

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

Health Condition(s) or Problem(s) studied

Recurrent or metastatic PD-L1-positive or negative squamous cell carcinoma of the head and neck (SCCHN).
MedDRA version: 18.0 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-

Product Name: Cetuximab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Cetuximab
CAS Number: 205923-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: Docetaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Docetaxel
CAS Number: 114977-28-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Paclitaxel
CAS Number: 33069-62-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Product Name: Methotrexate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Methotrexate
CAS Number: 59-05-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 12.5-

Product Name: 5-Fluorouracil
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: 5-fluorouracil
CAS Number: 51-21-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: Tegafur
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Tegafur
CAS Number: 17902-23-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Product Name: Capecitabine
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
CAS Number: 1543

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: -OS: time from the date of randomization until death due to any cause.
-PFS: time from the date of randomization until the date of objective disease progression or death.

Primary end point(s): - Overall survival: OS is defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last
recorded date on which the patient was known to be alive.
- Progression-free survival: PFS (per RECIST 1.1 as assessed by the BICR) will be defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment. However, if the patient progresses or dies after 2 or more missed visits, the patient will be censored at the time of the latest evaluable RECIST 1.1 assessment. If the patient has no evaluable visits or does not have baseline data, they will be censored at 0 days unless they die within 2 visits of baseline.

Secondary Objective: - To further assess the efficacy of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS, ORR, DoR, DCR, APF6, APF12, OS12, and OS18 and OS24
- To explore symptoms and HRQoL in patients treated with MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy versus SoC using the EORTC QLQ-C30 v3 and the H&N35 module

Main Objective: - To assess the efficacy of MEDI4736 monotherapy and MEDI4736 + tremelimumab combination therapy versus SoC in terms of PFS and OS

Secondary Outcome(s)

Secondary end point(s): - Objective response rate: ORR is defined as the number (%) of patients with at least 1 visit response of CR or PR and will be based on a subset of all randomized patients
- Duration of response: DoR is defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression.
- Disease control rate: DCR at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR in the first 6 months or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, ie, 161 days) following the start of treatment with IP. DCR at 12 months is defined as the percentage of patients who have a BoR of CR or PR in the first 12 months or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, ie, 329 days) following the start of treatment with IP.
- Proportion of patients alive and progression free at 6 months
- Proportion of patients alive and progression free at 12 months
- Proportion of patients alive at 12 months
- Proportion of patients alive at 18 months
- Proportion of patients alive at 24 months
- Best objective response: BoR is 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: Duration of study for individual patients

Secondary ID(s)

D4193C00002

2014-003863-40-HU

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 06/07/2015
Contact:

Results

• Results available: Yes
• Date Posted: 06/02/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003863-40/results