A clinical trial to study the efficacy of MEDI4736 alone or in combination with Tremelimumab versus standard of care in Recurrent or Metastatic Head and Neck Cancer
- Conditions
- Health Condition 1: null- Recurrent or Metastatic Squamous Cell Head and Neck Cancer
- Registration Number
- CTRI/2016/08/007169
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 760
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 or cytologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to local curative therapy with surgery or radiation therapy.
4. No prior systemic therapy for recurrent/metastatic disease.Systemic therapy given as part of multimodality treatment for locally advanced or locally recurrent disease is allowed.
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. For patients with OPC only: known HPV status prior to randomization.
7. Confirmed PD-L1â??positive or â??negative SCCHN by the Ventana SP263 IHC assay
- On newly acquired tumor tissue (preferred) or archival tissue ( <3 years old)
- If the patientâ??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.
- 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.
8. World Health Organization (WHO)/ECOG performance status of 0 or 1
9. 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 and the lesion measures at least 20 mm.
10. Patients must have no prior exposure to immune-mediated therapy, including anti CTLA-4, anti PD-1, antiâ??PD-L1, or antiâ??programmed cell death ligand 2 antibodies, excluding therapeutic anticancer vaccines. Exposure to other investigational agents may be permitted after discussion with the Sponsor.
11. 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 follows:
- Hemoglobin >=9 g/dL
- Absolute neutrophil count >=1500/mm3 (1.5 Ã? 109/L)
- Platelet count >=100000/mm3 (100 Ã? 109/L)
- Serum bilirubin <=1.5 Ã? the upper limit of normal (ULN). This will not apply to patients with confirm
Patients should not enter the study if any of the following exclusion criteria are fulfilled:
1. Histologically or cytologically confirmed head and neck cancer of any other primary anatomic location in the head and neck not specified in the inclusion criteria including patients with SCCHN of unknown primary or non-squamous histologies (eg, nasopharynx or salivary gland)
2. Tumor progression or recurrence within 6 months of last dose of platinum therapy given as part of multimodality treatment for locally advanced or locally recurrent disease.
3. Receipt of any radiotherapy or hormonal therapy for cancer treatment within 30 days prior to first dose of study treatment.
4. Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) 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.
5. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.
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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Grade >=2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, 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 a toxicity not reasonably expected to be exacerbated by treatment with their assigned IP (eg, hearing loss, gastrostomy tube) 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 unless otherwise indicated:
- 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 (eg, CT scan pre medication) and/or as anti-emetics for the SoC arm
9. History of allogeneic organ transplantation
10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis, Crohnâ??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; Gravesâ?? 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 ho
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method