BrUOG 355: Nivolumab to Tailored Radiation Therapy With Concomitant Cisplatin in the Treatment of Patients With Cervical Cancer
Condition: Cervical Cancer
MeSH terms: Uterine Cervical Neoplasms
Intervention: Nivolumab induction; Cisplatin; Radiation; Nivolumab with chemoradiation; Nivolumab maintenance
Intervention description: 2 doses Nivolumab 240mg IV; 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.; Total dose of 45 Gy in 25 fractions at 180 cGy/fx
Whole pelvic or extended field; Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.; Nivolumab 480 mg IV every 4 weeks for 2 years
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cervical cancer; Stage IB; Stage IIA; Stage IIB; Stage IIIA; Stage IIIB; Stage IVA

Summary:

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of the investigational drug in combination with radiation to learn whether
      the drug(s) works in treating a specific disease. In this study, researchers are studying
      three treatment arms, each using standard chemotherapy, with the drug cisplatin and radiation
      and the drug Nivolumab. Each treatment Arm will test the addition of Nivolumab at a different
      time point
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years.

          -  ECOG performance status ≤2

          -  Patients with histologically confirmed advanced cervical cancer (any cell type): FIGO
             Clinical stages IB, IIA, IIB, IIIA, IIIB, IVA.

          -  Participants must have normal organ and marrow function as defined below:

               1. absolute neutrophil count ≥1,500/mcL

               2. platelets ≥100,000/mcL

               3. total bilirubin within normal institutional limits

               4. AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

               5. creatinine Within normal institutional limits

          -  Neuropathy (sensory and motor) ≤ CTCAE v4.0 grade 1

          -  Patients with ureteral obstruction should undergo stent or nephrostomy tube placement
             prior to study entry. Any side effects or complications associated with stent
             placement that, in the opinion of the treating investigator, puts the patient at
             increased risk for treatment-related toxicity, must be resolved completely prior to
             study enrollment.

          -  Patients of child-bearing potential must have a negative serum pregnancy test prior to
             study entry (within 7 days prior to initiation of study treatment) and be practicing
             an effective form of contraception during study treatment and for 24 months (2 years)
             thereafter.

          -  Women should not breast-feed while on this study

          -  Patients must not be receiving any other investigational agent

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  All patients with a history of hearing loss are required to have an audiogram within
             28 days prior to initiating protocol therapy. If patient does not have a history of
             hearing loss this must be documented by treating physician.

        Exclusion Criteria:

          -  Participants with visceral metastases, including brain metastases.

          -  Uncontrolled intercurrent illness

          -  Patients who have received previous pelvic or abdominal radiation, cytotoxic
             chemotherapy, or previous therapy of any kind for this malignancy

          -  Patients who have circumstances that will not permit completion of this study or the
             required follow-up as per the treating physician

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer are excluded if there is any evidence of other malignancy
             being present within the last three years (2 years for invasive breast cancer).
             However, patients with a malignancy that is non-likely to require treatment, as per
             the treating physician, in the next 2 years, such as a completely resected, early
             stage breast cancer, are eligible. Patients are also excluded if their previous cancer
             treatment contraindicates this protocol therapy.

          -  Prior treatment with immunotherapy for any cancer, including immune checkpoint
             inhibitors or anti-CTLA4 agents

          -  Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal
             transplantation, that would require modification of radiation fields as documented by
             treating physician