BrUOG 355: Nivolumab to Tailored Radiation Therapy With Concomitant Cisplatin in the Treatment of Patients With Cervical Cancer

Study Overview
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Brief Summary
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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

Official Title
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BrUOG 355: A Pilot Feasibility Study Incorporating Nivolumab to Tailored Radiation Therapy With Concomitant Cisplatin in the Treatment of Patients With Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: Nivolumab induction
* Drug: Cisplatin
* Radiation: Radiation
* Drug: Nivolumab with chemoradiation
* Drug: Nivolumab maintenance


Participation Criteria
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Eligibility Criteria
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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: absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1A<br>Nivolumab during Chemo/RT with whole pelvic RT | Drug: Nivolumab induction<br>* 2 doses Nivolumab 240mg IV<br>Drug: Cisplatin<br>* 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.<br>Radiation: Radiation<br>* Total dose of 45 Gy in 25 fractions at 180 cGy/fx Whole pelvic or extended field<br>Drug: Nivolumab with chemoradiation<br>* Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.<br>|
| Experimental: Cohort 1B<br>Nivolumab during Chemo/RT with extended field | Drug: Nivolumab induction<br>* 2 doses Nivolumab 240mg IV<br>Drug: Cisplatin<br>* 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.<br>Radiation: Radiation<br>* Total dose of 45 Gy in 25 fractions at 180 cGy/fx Whole pelvic or extended field<br>Drug: Nivolumab with chemoradiation<br>* Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.<br>|
| Experimental: Cohort 2<br>Chemoradiation followed by Nivolumab Maintenance | Drug: Nivolumab induction<br>* 2 doses Nivolumab 240mg IV<br>Drug: Cisplatin<br>* 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.<br>Radiation: Radiation<br>* Total dose of 45 Gy in 25 fractions at 180 cGy/fx Whole pelvic or extended field<br>Drug: Nivolumab maintenance<br>* Nivolumab 480 mg IV every 4 weeks for 2 years<br>|
| Experimental: Cohort 3<br>Nivolumab during chemoradiation and then as maintenance | Drug: Nivolumab induction<br>* 2 doses Nivolumab 240mg IV<br>Drug: Cisplatin<br>* 40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.<br>Radiation: Radiation<br>* Total dose of 45 Gy in 25 fractions at 180 cGy/fx Whole pelvic or extended field<br>Drug: Nivolumab with chemoradiation<br>* Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.<br>Drug: Nivolumab maintenance<br>* Nivolumab 480 mg IV every 4 weeks for 2 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Number of patients that are alive without disease progression at time of analysis. | From start of study treatment through date of study completion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Patterns | Determination of the site of recurrence, loco-regional versus distant | From start of study treatment through date of study completion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, Stage IB, Stage IIA, Stage IIB, Stage IIIA, Stage IIIB, Stage IVA