| Eligibility |
Inclusion Criteria:
- Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol. Written informed consent and any locally required authorization obtained
from the patient/legal representative prior to performing any protocol-related
procedures, including screening evaluations
- Willing and ability to provide blood and tumor tissue samples
- Histologically confirmed HPV 16/18-positive cervical carcinoma (squamous cell
carcinoma; adenocarcinoma, adenosquamous carcinoma)
- Prior primary therapy with radical surgery, radical surgery followed by radiotherapy
(+/- chemo), chemotherapy, or primary concurrent chemoradiotherapy
- Cervical cancer recurrent after or refractory to only 1 prior first-line
platinum-based chemotherapy +/- bevacizumab.Measurable disease per Response Evaluation
Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- Eastern Cooperative Oncology Group performance status of 0-1
- Must have a life expectancy of at least 12 weeks
- Age > 18 years at time of study entry
- Body weight >30 kg
- Adequate normal organ and marrow function as defined below:
- Haemoglobin =9.0 g/dL (Note: The use of transfusion or other intervention to
achieve Hgb = 9.0 g/dl is acceptable)
- Absolute neutrophil count (ANC) > 1.5x10³per mm³
- Platelet count =75x10?/L (=75,000 per mm³)
- Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This will not
apply to patients with confirmed Gilbert's syndrome, who will be allowed only in
consultation with their physician.
- 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
- 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:
- If the patient is not in status post hysterectomy, women who are of child-bearing
potential willing to use effective methods of contraception including oral
contraceptives, intrauterine device, diaphragm with spermicides, and/or abstinence.
Women of childbearing potential who have a negative serum pregnancy test and must
agree to practice effective birth control throughout their participation in the
treatment phase of the study.
- 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. The following
age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
- Women =50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
hysterectomy).
- Status post hysterectomy
- 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.
Exclusion Criteria:
- Participation in another clinical study with an investigational product during the
last 4 weeks
- Concurrent enrollment 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, tumor embolization, monoclonal
antibodies) 4 weeks prior to the first dose of study drug
- 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
criteria
- Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after
consultation with the Study Physician.
- 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, 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 or with a wide field of
radiation 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 IP. 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:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
- 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
- Malignancy treated with curative intent and with no known active disease =5 years
before the first dose of IP 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
- History of leptomeningeal carcinomatosis
- Brain metastases or spinal cord compression. Patients with suspected brain metastases
at screening should have an MRI (preferred) or CT each preferably with IV contrast of
the brain prior to study entry
- Other epithelial tumors (except for adenosquamous carcinoma) defined by WHO
histological classification (including neuroendocrine tumors and undifferentiated
carcinoma)
- Non-epithelial cervical tumors defined by WHO histological classification: mesenchymal
tumors and tumor-like conditions; mixed epithelial and mesenchymal tumors; germ cell
tumors; lymphoid and myeloid tumors
- 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 any investigational products (BVAC-C or durvalumab). The following are
exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
- 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 IP and up to
30 days after the last dose of IP.
- 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 randomization or treatment in a previous durvalumab clinical study regardless of
treatment arm assignment.
- Prior therapy with any anti-PD-1 or anti-PD-L1 inhibitor including durvalumab
- Recurrent/refractory cervical cancer amenable to curative local therapy
- Known severe ischemic heart disease, severe arrythmia and other clinically significant
cardiac disease
- 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.
|
