Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer

January 3, 2024 updated by: Hospital Israelita Albert Einstein

Randomized Phase II Study to Evaluate Induction Nivolumab-Ipilimumab, Followed by Nivolumab With Chemoradiotherapy Versus Chemoradiotherapy for Advanced Cervical Cancer

A total of 112 patients with locally advanced cervical cancer will be randomized 1:1 to standard therapy with cisplatin-based chemoradiation or nivolumab-ipilimumab induction followed by cisplatin-based chemoradiation. The primary outcome will be 3-year disease-free survival.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with adenocarcinoma or squamous cell carcinoma of the cervix, FIGO Stage IB2-IB3 node positive or Stage IIB-IVA will be randomized to conventional cisplatin-based chemo-radiation or to 4 cycles of induction immunotherapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks, followed by cisplatin chemo-radiation with concurrent nivolumab 240mg every 2 weeks. Primary outcome will be 3-year progression-free survival.

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
      • Rio De Janeiro, Brazil, 20230-130
        • Not yet recruiting
        • INCA - Instituto Nacional Do Cancer
        • Contact:
        • Principal Investigator:
          • Andreia Melo, MD
      • São Paulo, Brazil, 05652-900
        • Recruiting
        • Hospital Israelita Albert Einstein
        • Contact:
          • Fernando Maluf
        • Contact:
        • Principal Investigator:
          • Fernando Maluf
      • São Paulo, Brazil, 01509-001
        • Not yet recruiting
        • AC Camargo Câncer Center
        • Contact:
        • Principal Investigator:
          • Natasha Carvalho, MD
      • São Paulo, Brazil, 04378-500
        • Recruiting
        • Hospital Municipal Vila Santa Catarina
        • Contact:
        • Principal Investigator:
          • Henrique A Helber, MD
    • Bahia
      • Salvador, Bahia, Brazil, 41810-011
        • Recruiting
        • Clinica AMO
        • Contact:
        • Principal Investigator:
          • Aknar Calabrich
    • Ceará
      • Fortaleza, Ceará, Brazil, 60335-480
        • Recruiting
        • CRIO -Centro Regional Integrado de Oncologia
        • Contact:
        • Principal Investigator:
          • Eduardo Cronemberger, MD
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil, 30130-100
        • Not yet recruiting
        • Hospital Das Clinicas Da Ufmg
        • Contact:
        • Principal Investigator:
          • Angélica Nogueira, MD
    • Paraná
      • Curitiba, Paraná, Brazil, 81520-060
        • Not yet recruiting
        • Hospital Erasto Gaertner
        • Contact:
        • Principal Investigator:
          • Reitan Ribeiro, MD
    • Pernambuco
      • Recife, Pernambuco, Brazil, 50070-460
        • Recruiting
        • Multi Oncoclinicas Recife
        • Contact:
        • Principal Investigator:
          • Carla Rameri, MD
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-001
        • Not yet recruiting
        • Hospital Sao Lucas - PUCRS
        • Contact:
        • Principal Investigator:
          • Fernanda Damian
    • Roraima
      • Boa Vista, Roraima, Brazil, 69310-000
        • Recruiting
        • Universidade Federal de Roraima
        • Contact:
        • Principal Investigator:
          • Allex Jardim, MD, PhD
    • Santa Catarina
      • Florianópolis, Santa Catarina, Brazil, 88034-000
        • Not yet recruiting
        • CEPON - Florianópolis
        • Contact:
        • Principal Investigator:
          • Anne Schmitz, MD
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Not yet recruiting
        • Hospital de Amor
        • Contact:
        • Principal Investigator:
          • Maria Fernanca Biazzotto, MD
      • São José Do Rio Preto, São Paulo, Brazil, 15090-000
        • Not yet recruiting
        • Hospital De Base de São José do Rio Preto - CIP São José
        • Contact:
        • Principal Investigator:
          • João Daniel, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female participants older than 18 years
  • Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO Stage IB2-IB3 node positive or Stage IIB-IVA
  • No prior chemotherapy, immune checkpoint inhibitors or radiotherapy for cervical cancer
  • WHO/ECOG performance status of 0-1
  • At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion at baseline.

Exclusion Criteria:

  • Diagnosis of small cell (neuroendocrine) histology cervical cancer
  • Intent to administer a fertility-sparing treatment regimen
  • Undergone a previous hysterectomy
  • Evidence of metastatic disease per RECIST 1.1 including lymph nodes ≥15 mm (short axis) above the L1 cephalad body or outside the planned radiation field.
  • History of allogeneic organ transplantation
  • Active or prior documented autoimmune or inflammatory disorders
  • Uncontrolled intercurrent illness
  • History of another primary malignancy and active primary immunodeficiency
  • Patients with active infection

Laboratory values that fall into:

  1. WBC count (WBC) < 2000/μL ;
  2. Neutrophil count < 1500/μL;
  3. Platelet count < 100 x 103/μL;
  4. Hemoglobin level < 9.0 g/dL;

  5. Serum creatinine > 1.5 x upper limit of normal (ULN) unless creatinine clearance is

    ≥ 40 mL/min (measured or calculated using the Cockcroft-Gault formula);

  6. Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): > 3.0 x ULN;
  7. Total bilirubin > 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN);

  8. Any positive test result for hepatitis B virus or hepatitis C virus that indicates the presence of the virus, for example, positive Hepatitis B surface antigen (HBsAg, Australia antigen) or Hepatitis C antibodies (anti- HCV) positive (unless the HCV-RNA is negative).

    • Participants with a condition requiring systemic treatment or with corticosteroids (>10 mg daily of a prednisone equivalent) or other immunosuppressive drugs within 14 days of initiating study treatment.
    • Pregnant or breastfeeding woman

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Chemoradiation
Traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week or carboplatin AUC 2/week
Radiation: Chemoradiation
Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w
Other Names:
  • Cisplatin-based chemoradiation
Experimental: Immunotherapy
4 cycles of induction therapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks followed by traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week (or carboplatin AUC 2/week) with concurrent nivolumab 240mg every 2 weeks.
Radiation: Chemoradiation
Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w
Other Names:
  • Cisplatin-based chemoradiation
Drug: Nivolumab 40 mg in 4 ml Injection
Nivolumab 1mg/kg every 3 weeks for 4 cycles prior to radiation and 240mg every 2 weeks with concurrent radiation
Other Names:
  • Opdivo
Drug: Ipilimumab 200 MG in 40 ML Injection
Ipilimumab 3mg/kg every 3 weeks for 4 cycles prior to radiation
Other Names:
  • Yervoy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3-year progression-free survival
Time Frame: 3 years
No evidence of disease recurrence/regrowth after 3 years of follow-up
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3-year overall survival
Time Frame: 3 years
Rate of survival 3 years after the end of chemoradiation
3 years
Objective response rate
Time Frame: 90 days after the end of chemoradiation
RECIST response
90 days after the end of chemoradiation
Response duration
Time Frame: Through study completion, an average of 3 year
Time from maximum response to disease progression
Through study completion, an average of 3 year
To evaluate health related quality of life (HRQoL): defined as the change from baseline of disease-related symptoms and quality of life of patients undergoing treatment Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer
Time Frame: Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
Evaluate health related quality of life using the instrument EORTC QLQ-C30 v3 based on European Organization for Research and Treatment of Cancer (EORTC). The EORTC QLQ-C30 v3 questionnaire, consisting of 30 questions covering 15 domains, divided into three distinct scales: state scale global health and quality of life (it has only one domain, global health measure); functional scale (physical function, role performance, emotional function, cognitive function and social function domains); and symptom scale (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea and financial difficulties). The scores on each scale range from 0 - 100. The global and functional health scales indicate better quality of life as their score approaches 100. For the symptoms scale, the analysis is inverse, with better performance for quality of life when the scores approach the score minimum (zero).
Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
Evaluate health related quality of life using supplemental cervical cancer module (EORTC CX24) to evaluate patients submitted to treatment with Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer.
Time Frame: Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
The EORTC - CX24 questionnaire contains 24 questions, divided into three multiple-item scales and six single-item scales, of which 11 refer to symptoms (questions 31-37, 39 and 41-43), three about body image. (questions 45-47), four questions on sexual/vaginal function (questions 50-53), one on lymphedema (question 38), one for evaluation of peripheral neuropathy (question 40), one for evaluation of menopausal symptoms (question 44) ), one on sexual concerns (question 48), one on sexual activity (question 49) and one on sexual pleasure (question 54). The answers are transformed into a score from 0 - 100 and calculated separately for each scale.
Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
Treatment-related toxicity
Time Frame: Through study completion, an average of 3 year
Treatment-related toxicity according to CTCAE version 4.0 (Common Toxicity Criteria for Adverse Events )
Through study completion, an average of 3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Israelita Albert Einstein

Collaborators

Bristol-Myers Squibb
Brava

Investigators

  • Principal Investigator: Fernando Maluf, MD, Hospital Israelita Albert Einstein

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 30, 2022

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

March 31, 2028

Study Registration Dates

First Submitted

July 22, 2022

First Submitted That Met QC Criteria

August 5, 2022

First Posted (Actual)

August 8, 2022

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 3, 2024

Last Verified

January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BRAVA- Cervical - SGPP 5031-21

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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