| Eligibility |
Inclusion Criteria:
Histologically confirmed diagnosis of cervical squamous cell carcinoma stage IB3 to IVA,
(FIGO 2018)
- Patients requiring RT-CT therapy as standard of care
- Age =18
- Patient accepting to undergo a new cervix biopsy
- Adequate marrow function:
- White blood cell (WBC) >2000/mm3 (stable off any growth factor within 4 weeks of
first study drug administration)
- Neutrophils >1500/ mm3 (stable off any growth factor within 4 weeks of first
study drug administration)
- Platelets > 100× 103/mm3 (transfusion to achieve this level is not permitted
within 2 weeks of first study drug administration)
- Hemoglobin > 8 g/dL (transfusion to achieve this level is not permitted within 2
weeks of first study drug administration)
- Adequate other organ functions:
- ALT and AST < 3× institutional ULN
- Total bilirubin < 1.5× institutional ULN (except subjects with Gilbert's Syndrome
who must have normal direct bilirubin)
- Normal thyroid function, subclinical hypothyroidism (thyroid-stimulating hormone
[TSH] < 10 mIU/mL) or have controlled hypothyroidism on appropriate thyroid
supplementation
- Serum creatinine < 2× ULN or creatinine clearance (CrCl) > 40 mL/min (measured
using the Cockcroft-Gault formula or the MDRD formula for patients older than 65
years-old
- General Health as evidenced by PS =2
- Covered by a medical insurance
- Signed and dated informed consent form prior to any study-specific procedure.
- Stated willingness to comply with all study procedures and availability for the
duration of the study
- Women of childbearing potential must have a negative serum or urine pregnancy test For
females of reproductive potential: use of highly effective contraception and for at
least 5 months after administration of the last dose of nivolumab. A woman is
considered to be of childbearing potential if she is postmenarcheal, has not reached a
postmeno-pausal state (= 12 continuous months of amenorrhea with no identified cause
other than menopause), and has not undergone surgical sterilization (removal of
ovaries, fallopian tubes, and/or uterus).
- All subjects must consent to allow the acquisition of blood samples, FFPE tumor
tissue, either a block or 15 to 20 unstained slides, and fresh tumor for performance
of correlative studies.
Exclusion Criteria:
- Pregnant or breastfeeding women.
- Patient concurrently using other approved or investigational antineoplastic agents.
- Patient candidate for neo adjuvant CT before RT-CT
- Any contraindication to nivolumab or ipilimumab treatments as per Nivolumab and
Ipilimumab Investigator's Brochure
- Prior therapy with an immune checkpoint inhibitor
- Prior history of other malignancies other than study disease (except for basal cell or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the
patient has been free of the disease for at least 3 years.
- Immune-deficient status (patients with HIV, immunosuppressive treatment,
haematological malignancies, and previous organ transplantation)
- History of any chronic hepatitis as evidenced by:
- Positive test for hepatitis B surface antigen
- Positive test for qualitative hepatitis C viral load (by polymerase chain
reaction [PCR])
Note: Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by
PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion
criterion
- Uncontrolled or significant cardiovascular disease including, but not limited to, any
of the following:
- Myocardial infarction or stroke/transient ischemic attack within the past 6
months
- Uncontrolled angina within the past 3 months
- History of other clinically significant heart disease (eg, cardiomyopathy,
congestive heart failure with New York Heart Association functional
classification III-IV, pericarditis, significant pericardial effusion, or
myocarditis)
- Any history of clinically significant arrhythmias (such as ventricular
tachycardia, ventricular fibrillation, or torsades de pointes)
- QT interval corrected for heart rate using Fridericia's formula (QTcF)
prolongation > 480 msec
- Cardiovascular disease-related requirement for daily supplemental oxygen therapy
- Subjects with known or suspected CNS metastases, untreated CNS metastases, are
excluded.
Note: However, subjects with controlled brain metastases will be allowed to enroll.
Controlled brain metastases are defined as no radiographic progression for at least 4 weeks
following radiation and/or surgical treatment (or 4 weeks of observation if no intervention
is clinically indicated), and off of steroids for at least 2 weeks, and no new or
progressive neurological signs and symptoms.
• Patients requiring concomitant treatment with therapeutic doses of anticoagulants will
not be eligible for this clinical trial.
Note: Patients treated with low dose of anticoagulants for thrombo-embolic events
prophylaxis are allowed.
• Any major surgery within 4 weeks of study drug administration. Subjects must have
recovered from the effects of major surgery or significant traumatic injury at least 14
days before the first dose of study drug.
Note: Pelvic and aortic dissection is not considered as traumatic surgery, and therefore
can be performed if clinically indicated.
- Subjects with active, known or suspected autoimmune disease. Note: Subjects with skin
disorders (such as vitiligo, psoriasis or alopecia), type I diabetes mellitus,
hypothyroidism only requiring hormone replacement or conditions not expected to recur
in the absence of an external trigger are permitted to enroll.
- Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration.
Note: Inhaled or topical steroids, and adrenal replacement doses are permitted in the
absence of active autoimmune disease.)
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