Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer

NCT05492123 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BRAVA- Cervical - SGPP 5031-21
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Uterine Cervical Neoplasms

Keywords

Uterine Cervical Neoplasms; Nivolumab; Ipilimumab; Chemoradiation; Anti-PD1; Anti-PDL1; Anti-CTLA4; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• 3-year progression-free survival

  No evidence of disease recurrence/regrowth after 3 years of follow-up

  3 years

Secondary Outcomes (6)

• 3-year overall survival

  3 years

• Objective response rate

  90 days after the end of chemoradiation

• Response duration

  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

  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.

  Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).

Study Arms (2)

Standard Chemoradiation

ACTIVE COMPARATOR

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

Immunotherapy

EXPERIMENTAL

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.

Drug: Nivolumab 40 mg in 4 ml Injection; Drug: Ipilimumab 200 MG in 40 ML Injection; Radiation: Chemoradiation

Interventions

Nivolumab 40 mg in 4 ml Injection DRUG

Nivolumab 1mg/kg every 3 weeks for 4 cycles prior to radiation and 240mg every 2 weeks with concurrent radiation

Also known as: Opdivo

Immunotherapy

Ipilimumab 200 MG in 40 ML Injection DRUG

Ipilimumab 3mg/kg every 3 weeks for 4 cycles prior to radiation

Also known as: Yervoy

Immunotherapy

Chemoradiation RADIATION

Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w

Also known as: Cisplatin-based chemoradiation

Immunotherapy; Standard Chemoradiation

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• WBC count (WBC) \< 2000/μL ;
• Neutrophil count \< 1500/μL;
• Platelet count \< 100 x 103/μL;
• Hemoglobin level \< 9.0 g/dL;
• Serum creatinine \> 1.5 x upper limit of normal (ULN) unless creatinine clearance is

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead
• Bristol-Myers Squibb: collaborator
• Brava: collaborator

Study Sites (14)

CRIO -Centro Regional Integrado de Oncologia

Fortaleza, Ceará, 60335-480, Brazil

RECRUITING

Clinica AMO

Salvador, Estado de Bahia, 41810-011, Brazil

RECRUITING

Hospital das Clinicas da UFMG

Belo Horizonte, Minas Gerais, 30130-100, Brazil

NOT YET RECRUITING

Hospital Erasto Gaertner

Curitiba, Paraná, 81520-060, Brazil

NOT YET RECRUITING

Multi Oncoclinicas Recife

Recife, Pernambuco, 50070-460, Brazil

RECRUITING

Hospital São Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-001, Brazil

NOT YET RECRUITING

Universidade Federal de Roraima

Boa Vista, Roraima, 69310-000, Brazil

RECRUITING

CEPON - Florianópolis

Florianópolis, Santa Catarina, 88034-000, Brazil

NOT YET RECRUITING

Hospital de Amor

Barretos, São Paulo, 14784-400, Brazil

NOT YET RECRUITING

Hospital De Base de São José do Rio Preto - CIP São José

São José do Rio Preto, São Paulo, 15090-000, Brazil

NOT YET RECRUITING

INCA - Instituto Nacional do Cancer

Rio de Janeiro, 20230-130, Brazil

NOT YET RECRUITING

AC Camargo Cancer Center

São Paulo, 01509-001, Brazil

NOT YET RECRUITING

Hospital Municipal Vila Santa Catarina

São Paulo, 04378-500, Brazil

RECRUITING

Hospital Israelita Albert Einstein

São Paulo, 05652-900, Brazil

RECRUITING

Related Publications (3)

• Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.

  PMID: 19001332 BACKGROUND

• Naumann RW, Hollebecque A, Meyer T, Devlin MJ, Oaknin A, Kerger J, Lopez-Picazo JM, Machiels JP, Delord JP, Evans TRJ, Boni V, Calvo E, Topalian SL, Chen T, Soumaoro I, Li B, Gu J, Zwirtes R, Moore KN. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. J Clin Oncol. 2019 Nov 1;37(31):2825-2834. doi: 10.1200/JCO.19.00739. Epub 2019 Sep 5.

  PMID: 31487218 BACKGROUND

• Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecol Oncol. 2020 Apr;157(1):161-166. doi: 10.1016/j.ygyno.2019.12.034. Epub 2020 Jan 7.

  PMID: 31924334 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Nivolumab; Injections; Ipilimumab; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics; Combined Modality Therapy; Radiotherapy

Study Officials

• Fernando Maluf, MD

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diogo Bugano, MD

CONTACT

+55-11-2151-0240; diogo.gomes@einstein.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective randomized trial, stratified by center, disease stage and type of radiation

Study Record Dates

• First Submitted: July 22, 2022
• First Posted: August 8, 2022
• Study Start: August 30, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: January 5, 2024

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (14)