Study of MEDI4736 Monotherapy, Tremelimumab Monotherapy, and MEDI4736 in Combination with Tremelimumab in Patients with SCCH
- Conditions
- Patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck (SCCHN)MedDRA version: 20.0Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-003717-29-DE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
1) Age =18 years at the time of screening;
2) Written informed consent and any locally required authorization;
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 that 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. Patients who received concurrent chemo-radiation aas part of treatment of their recurrent disease are also 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 acuired 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-negative 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 part of the Screening process for another AstraZeneca/Medimmune study, this test can be used for the determination of eligibility;
7) WHO/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 short axis =15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines;
9) Patients must have no prior exposure to immune-mediated therapy, including other 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 upper limit of normal (ULN), 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;
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 for 12 months without an alternative medical cause.
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 96
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144
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;
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 is acceptable;
4) Prior randomization or treamtent in a previous MEDI4736 and / or tremelimumab clinical study regardless of treamtent arm assignement 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 Grade =2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Study Physician, **- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with their assigned IP 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 their assigned IP. The following are exceptions to this criterion: * - Intranasal, inhaled, topical steroids, or local steroid injections, ** - 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, 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. The following are exceptions to this criterion: * - Patients with vitiligo or alopecia, ** - Patients with hypothyroidism 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 tremelimumab, or compromise the ability of the patient to give written informed consent;
12) History of another primary malignancy except for: * - Malignancy
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method