| Eligibility |
Inclusion Criteria:
- AGE >18
- Able to provide informed consent.
- Pathological stage T1B or T2 esophageal or non-metastatic gastro-esophageal
adenocarcinoma, squamous cell cancer or mixed histology.
- Ineligible for or declining esophagectomy.
- Completed endoscopic mucosal resection (EMR) or endoscopic submucosal dissection
(ESD).
- Body weight >30kg
- Adequate normal organ and marrow function as defined below:
1. Haemoglobin =9.0 g/dL
2. Absolute neutrophil count (ANC) =1.0 × 109 /L
3. Platelet count =75 × 109/L
4. Serum bilirubin =1.5 x institutional upper limit of normal (ULN). <<This will not
apply to patients 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. Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40
mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL)
- Patient 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.
- Must have a life expectancy of at least 12 weeks
Exclusion Criteria:
- • Participation in another clinical study with an investigational product during the
last 4 weeks.
- Concurrent enrolment in another clinical study unless it is an observational
(non-interventional) clinical study or during the follow-up period of an
interventional study.
- Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumour embolization,
monoclonal antibodies) =15 days prior to the first dose of study drug. If
sufficient wash-out time has not occurred due to the schedule or PK properties of
an agent, a longer wash-out period will be required, as agreed by AstraZeneca and
the investigator.
- Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with
the exception of alopecia and vitiligo.
1. Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Study Physician.
2. Patients with irreversible toxicity not reasonably expected to be
exacerbated by treatment with durvalumab may be included only after
consultation with the Study Physician.
- Any concurrent chemotherapy, investigative product (IP), biologic, or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for
non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
- Radiotherapy treatment to more than 30% of the bone marrow within 4 weeks of the
first dose of study drug.
- Major surgical procedure (as defined by the Investigator) within 28 days prior to
the first dose of durvalumab. Note: Local surgery of isolated lesions for
palliative intent is acceptable.
- History of allogenic organ transplantation.
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis
[with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,
rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions
to this criterion:
1. Patients with vitiligo or alopecia.
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement.
3. Any chronic skin condition that does not require systemic therapy.
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician.
5. Patients with celiac disease controlled by diet alone.
- 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, serious chronic gastrointestinal conditions associated with diarrhea, or
psychiatric illness/social situations that would limit compliance with study
requirement, substantially increase risk of incurring AEs or compromise the
ability of the patient to give written informed consent.
- History of another primary malignancy except for
1. Malignancy treated with curative intent and with no known active disease =5
years before the first dose of durvalumab and of low potential risk for
recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
3. Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Patients with brain or any other brain metastases
- History of active primary immunodeficiency
- 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. 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.
- Current or prior use of immunosuppressive medication within 14 days before the
first dose of durvalumab. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
intra articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine whilst receiving
durvalumab and up to 30 days after the last dose of durvalumab.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study
drug excipients.
- Prior randomisation or treatment in a previous durvalumab clinical study
regardless of treatment arm assignment.
- Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4:
1. Must not have experienced a toxicity that led to permanent discontinuation
of prior immunotherapy.
2. All AEs while receiving prior immunotherapy must have completely resolved or
resolved to baseline prior to screening for this study.
3. Must not have experienced a =Grade 3 immune related AE or an immune related
neurologic or ocular AE of any grade while receiving prior immunotherapy.
NOTE: Patients with endocrine AE of =Grade 2 are permitted to enroll if they
are stably maintained on appropriate replacement therapy and are
asymptomatic.
4. Must not have required the use of additional immunosuppression other than
corticosteroids for the management of an AE, not have experienced recurrence
of an AE if re-challenged, and not currently require maintenance doses of >
10 mg prednisone or equivalent per day.
- Judgment by the investigator that the patient is unsuitable to participate in the
study and the patient is unlikely to comply with study procedures, restrictions
and requirements.
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