| Eligibility |
Inclusion Criteria:
1. Written informed consent and any locally-required authorization (e.g., HIPAA in the
USA, EU Data Privacy Directive in the EU) obtained from the subject prior to
performing any protocol-related procedures, including screening evaluations
2. Age > 18 years at time of study entry, age > 20 years for Japanese subjects.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Life expectancy of > 12 weeks
5. Adequate normal organ and marrow function as defined below:
1. Hemoglobin= 9.0 mmol/L
2. Absolute neutrophil count (ANC) = 1.5 x 109/L (> 1500 per mm3)
3. Platelet count = 100 x 109/L (>100,000 per mm3)
4. Serum bilirubin = 1.5 x institutional upper limit of normal (ULN). (This will not
apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
or hepatic pathology), who will be allowed only in consultation with their
physician)
5. AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be = 5x ULN
6. Serum creatinine CL>40 mL/min by MDRD
6. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by
history: =60 years old and no menses for =1 year without an alternative medical cause;
OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of
bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
7. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.
8. Histological proven recurrent or metastatic squamous cell cancer of the head and neck
9. At least one lesion with a tumor size =1 cm
Exclusion Criteria:
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site). Previous enrollment in the present study
2. Participation in another clinical study with an investigational product during the
last 4 weeks
3. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
4. History of another primary malignancy except for:
- 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
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease e.g., cervical
cancer in situ
5. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) 28 days prior to the first dose of study drug
28 days prior to the first dose of study drug for subjects who have received prior
TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or
mitomycin C).
6. Mean QT interval corrected for heart rate (QTc) = 470 ms calculated from 3
electrocardiograms (ECGs) using Frediricia's Correction
7. Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or
systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of
prednisone, or an equivalent corticosteroid
8. Any unresolved toxicity (>CTCAE grade 2) from previous anti-cancer therapy. Subjects
with irreversible toxicity that is not reasonably expected to be exacerbated by the
investigational product may be included (e.g., hearing loss, peripherally neuropathy)
9. Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1
10. Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.
11. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)
12. History of primary immunodeficiency
13. History of allogeneic organ transplant
14. History of hypersensitivity to durvalumab or any excipients
15. History of hypersensitivity to the combination or comparator agent (If applicable)
16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any subject known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the subject to give written informed consent
17. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.
18. History of leptomeningeal carcinomatosis
19. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab
20. Female subjects who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control:
Female patient of child-bearing potential
- Females of childbearing potential who are sexually active with a non sterilized
male partner must use at least 1 highly effective method of contraception (Table
1) from the time of screening and must agree to continue using such precautions
for 180 days after the last dose of durvalumab + tremelimumab combination therapy
or 90 days after the last dose of durvalumab monotherapy (based on 5x the
half-life of durvalumab or tremelimumab). Non-sterilized male partners of a
female patient must use male condom plus spermicide throughout this period.
Cessation of birth control after this point should be discussed with a
responsible physician. Not engaging in sexual activity for the total duration of
the drug treatment and the drug washout period is an acceptable practice;
however, periodic abstinence, the rhythm method, and the withdrawal method are
not acceptable methods of birth control. Female patients should also refrain from
breastfeeding throughout this period.
- Male patients with a female partner of childbearing potential. Non-sterilized
males who are sexually active with a female partner of childbearing potential
must use a male condom plus spermicide from screening through 180 days after
receipt of the final dose of durvalumab + tremelimumab combination therapy or 90
days after receipt of the final dose of durvalumab monotherapy. Not engaging in
sexual activity is an acceptable practice; however, occasional abstinence, the
rhythm method, and the withdrawal method are not acceptable methods of
contraception. Male patients should refrain from sperm donation throughout this
period.
21. Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
22. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids.
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