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

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

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

Study Overview

• Status: Terminated
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Nivolumab induction; Drug: Cisplatin; Radiation: Radiation; Drug: Nivolumab with chemoradiation; Drug: Nivolumab maintenance

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: Bristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants Hospital of Rhode Island
• Investigators: Principal Investigator: Don Dizon, MD, Brown University Oncology Research Group (BrUOG)

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2018
• Primary Completion (Actual): November 13, 2020
• Study Completion (Actual): November 13, 2020

Study Registration Dates

• First Submitted: May 4, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 26, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: cervical cancer; Stage IB; Stage IIA; Stage IIB; Stage IIIA; Stage IIIB; Stage IVA
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Cisplatin; Nivolumab
• Other Study ID Numbers: BrUOG 355

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No