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

NCT ID: NCT03527264

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-08
• Study Completion Date: 2020-11-13

Brief 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

Conditions

Cervical Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1A

Nivolumab during Chemo/RT with whole pelvic RT

Group Type: EXPERIMENTAL

Nivolumab induction

Intervention Type: DRUG

2 doses Nivolumab 240mg IV

Cisplatin

Intervention Type: DRUG

40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.

Radiation

Intervention Type: RADIATION

Total dose of 45 Gy in 25 fractions at 180 cGy/fx

Whole pelvic or extended field

Nivolumab with chemoradiation

Intervention Type: DRUG

Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.

Cohort 1B

Nivolumab during Chemo/RT with extended field

Group Type: EXPERIMENTAL

Nivolumab induction

Intervention Type: DRUG

2 doses Nivolumab 240mg IV

Cisplatin

Intervention Type: DRUG

40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.

Radiation

Intervention Type: RADIATION

Total dose of 45 Gy in 25 fractions at 180 cGy/fx

Whole pelvic or extended field

Nivolumab with chemoradiation

Intervention Type: DRUG

Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.

Cohort 2

Chemoradiation followed by Nivolumab Maintenance

Group Type: EXPERIMENTAL

Nivolumab induction

Intervention Type: DRUG

2 doses Nivolumab 240mg IV

Cisplatin

Intervention Type: DRUG

40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.

Radiation

Intervention Type: RADIATION

Total dose of 45 Gy in 25 fractions at 180 cGy/fx

Whole pelvic or extended field

Nivolumab maintenance

Intervention Type: DRUG

Nivolumab 480 mg IV every 4 weeks for 2 years

Cohort 3

Nivolumab during chemoradiation and then as maintenance

Group Type: EXPERIMENTAL

Nivolumab induction

Intervention Type: DRUG

2 doses Nivolumab 240mg IV

Cisplatin

Intervention Type: DRUG

40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.

Radiation

Intervention Type: RADIATION

Total dose of 45 Gy in 25 fractions at 180 cGy/fx

Whole pelvic or extended field

Nivolumab with chemoradiation

Intervention Type: DRUG

Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.

Nivolumab maintenance

Intervention Type: DRUG

Nivolumab 480 mg IV every 4 weeks for 2 years

Interventions

Nivolumab induction

2 doses Nivolumab 240mg IV

Intervention Type: DRUG

Cisplatin

40 mg/m2 of cisplatin: Dosing on Days: 1, 8, 15, 22, 29, 36 beginning on day 1 of radiation therapy.

Intervention Type: DRUG

Radiation

Total dose of 45 Gy in 25 fractions at 180 cGy/fx

Whole pelvic or extended field

Intervention Type: RADIATION

Nivolumab with chemoradiation

Nivolumab 240mg IV every 14 days (+/- 3 days) for 3 doses, administered concomitantly during chemoradiation and beginning day 1 of Radiation.

Intervention Type: DRUG

Nivolumab maintenance

Nivolumab 480 mg IV every 4 weeks for 2 years

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Rhode Island Hospital

OTHER

Sponsor Role: collaborator

The Miriam Hospital

OTHER

Sponsor Role: collaborator

Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Brown University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Don Dizon, MD

Role: PRINCIPAL_INVESTIGATOR

Brown University Oncology Research Group (BrUOG)

Locations

Rhode Island Hospital

Providence, Rhode Island, United States

Women and Infants Hospital

Providence, Rhode Island, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

BrUOG 355

Identifier Type: -

Identifier Source: org_study_id