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- Conditions
- Patients with recurrent and/or metastatic platinum refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN), with poor prognosis and no effective chemotherapy options.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-000424-10-FR
- Lead Sponsor
- ICANCER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 173
1. Adult men and women = 18 years.
2. Histologically confirmed recurrent and/or metastatic SCCHN (oral cavity, pharynx, larynx), stage III/IV and not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
3. Patients with Eastern Cooperative Oncology Group (ECOG) performance status =2.
4. Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of tumor for SCC of the oropharynx
5. Tumor progression or recurrence after a platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting. In the adjuvant or primary setting, the recurrence must have occurred within 6 months after the last dose of platinum therapy. Clinical progression after platinum therapy is an allowable event for entry and is defined as progression of a lesion at least 10 mm in size that is amenable to caliper measurement (eg superficial skin lesion as per RECIST 1.1) or a lesion that has been visualized and photographically recorded with measurements and shown to have progressed.
6. Measurable disease by CT or MRI per RECIST 1.1 criteria
7. Prior curative radiation therapy must have been completed at least 4 weeks prior to study drug administration. Prior focal palliative radiotherapy must have been completed at least 2 weeks before study drug administration.
8. Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration
9. Patients with brain metastases will be eligible if they are: asymptomatic, without edema, not on corticosteroids, have been treated and there is no magnetic resonance imaging (except where contraindicated in which CT scan is acceptable) evidence of progression for at least 4 weeks after treatment is complete
10. Screening laboratory values must meet the following criteria (using CTCAE v4) and should be obtained within 7 days prior to the first study drug administration :
a. WBC = 2000/µL
b. Polynuclear neutrophils = 1.5 x 109/L
c. Platelets= 75 x 109/L
d. Hemoglobin = 8.0 g/mL
e. ALAT/ASAT= 3.0 x ULN in the absence of liver metastases or = 5x ULN in the presence of liver metastases
f. Total Bilirubin = 1.5 x ULN (except Gilbert Syndrome : < 3.0 mg/dL)
g. Creatinine clearance = 40 mL/min (measured or calculated by Cockroft and Gault formula) or serum creatinine =2.0 x ULN
11. Calcium levels must be normalized and maintained within normal limits for study entry and on treatment. Medical management of calcium levels is permitted. Note: Normal calcium levels may be based on ionized calcium or adjusted for albumin.
12. Subjects with an initial magnesium < 0.5 mmol/L (1.2 mg/dL) may receive corrective magnesium supplementation but should continue to receive either prophylactic weekly infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at the investigator’s discretion.
13. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods o
1. Histologically confirmed recurrent and/or metastatic carcinomas of the nasopharynx, squamous cell carcinoma of unknown primary, and salivary gland or non-squamous histologies (eg mucosal melanoma) are not allowed.
2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
3. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
5. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
6. Patients having received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
7. Patients receiving anti-cancer therapies must be discontinued at least 2 weeks prior to administration of study drug. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks before administration of study drug.
8. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. Subjects with toxicities attributed to systemic prior anticancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
9. Patients with positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
10. Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
11. Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug. The use of the inactivated seasonal influenza vaccine (Fluzone®) is allowed.
12. Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator’s opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events.
13. History of un
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