Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer

NCT05492123RecruitingPHASE2INTERVENTIONAL

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.

Key Facts

Lead Sponsor

Hospital Israelita Albert Einstein

Enrollment

112

Start Date

2022-08-30

Completion Date

2026-12-31

Study Type

INTERVENTIONAL

Official Title

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

Interventions

Nivolumab 40 mg in 4 ml InjectionIpilimumab 200 MG in 40 ML InjectionChemoradiation

Conditions

Uterine Cervical Neoplasms

Eligibility

Age Range

18 Years – 95 Years

Sex

FEMALE

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

Outcome Measures

Primary Outcomes

3-year progression-free survival

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

Time frame: 3 years

Secondary Outcomes

3-year overall survival

Rate of survival 3 years after the end of chemoradiation

Time frame: 3 years

Objective response rate

RECIST response

Time frame: 90 days after the end of chemoradiation

Response duration

Time from maximum response to disease progression

Time frame: 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

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).

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 supplemental cervical cancer module (EORTC CX24) to evaluate patients submitted to treatment with Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer.

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.

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

Treatment-related toxicity

Treatment-related toxicity according to CTCAE version 4.0 (Common Toxicity Criteria for Adverse Events )

Time frame: Through study completion, an average of 3 year

Locations

CRIO -Centro Regional Integrado de Oncologia, Fortaleza, Brazil

Clinica AMO, Salvador, Brazil

Hospital das Clinicas da UFMG, Belo Horizonte, Brazil

Hospital Erasto Gaertner, Curitiba, Brazil

Multi Oncoclinicas Recife, Recife, Brazil

Hospital São Lucas - PUCRS, Porto Alegre, Brazil

Universidade Federal de Roraima, Boa Vista, Brazil

CEPON - Florianópolis, Florianópolis, Brazil

Hospital de Amor, Barretos, Brazil

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

INCA - Instituto Nacional do Cancer, Rio de Janeiro, Brazil

AC Camargo Cancer Center, São Paulo, Brazil

Hospital Municipal Vila Santa Catarina, São Paulo, Brazil

Hospital Israelita Albert Einstein, São Paulo, Brazil

Linked Diseases

Uterine Cervical Neoplasms

Uterine Cervical Neoplasms — a type of gynecological cancer.

Linked Papers

2020-01-07

Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002)

Patients with persistent/recurrent cervical cancer following platinum-based chemotherapy have limited therapeutic options. The Gynecologic-Oncology-Group conducted a phase II trial to assess efficacy and tolerability of nivolumab, an immune checkpoint inhibitor, in persistent/recurrent cervical carcinoma. Key eligibility criteria included persistent/recurrent cervical cancer, failure of prior systemic therapy and ECOG PS 0-1. Nivolumab 3 mg/kg was given IV every 2 wk. until disease progression or intolerable toxicity. Response was assessed every 8 wk. for 6 months and every 12 wk. thereafter. The primary endpoints were objective response as assessed by RECIST 1.1. The study used a 2-stage group sequential design. PD-L1 expression was evaluated in tumor specimens by immunohistochemistry (IHC) using a combined-positive-score (CPS) cutoff of ≥1%. Of 26 enrolled patients with persistent/recurrent cervical cancer, 25 were evaluable for response/toxicity with a median age of 45. 36% had ECOG PS of 1, and 100% had received one prior systemic chemotherapy regimen. PD-L1 expression (≥1%) was identified in 77.3% of tumor samples. As of 03/05/19, all patients were off study treatment; median follow-up for survival status was 32 months (range, 2-41.5). There were 21 (84%) patients with a treatment-related adverse event (TRAE) and most were grades 1-2. Six (24%) patients had grade 3 TRAEs with 1 discontinuing nivolumab due to hepatic toxicity. No grade 5 TRAEs occurred, and 2 patients had grade 4 TRAEs. One confirmed partial response (4%; 90% CI, 0.4%-22.9%), duration of response 3.8 months. Thirty-six percent of patients had stable disease (SD) (9/25; 90% CI, 20.2%-54.4%); the median duration of SD was 5.7 months (range, 3.5-12.7). Estimated PFS and OS at 6 months were 16% and 78.4%, respectively. Single agent nivolumab exhibited low antitumor activity and an acceptable safety profile in patients with persistent/recurrent cervical cancer previously treated with platinum-based chemotherapy.

Linked Investigators

Alessandro D. Santin

Michael Frumovitz

Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer