Chemo-radio-immunotherapy With Nivolumab and Ipilimumab Treatment in Locally Advanced Cervical Cancer Patients

NCT05504642 | Withdrawn Phase 2 DMC

• 1 other identifier: Uni-Koeln-4513
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to use Chemo-radio-immunotherapy and maintenance therapy with Nivolumab and Ipilimumab in order to achieve improved outcome in patients with locally advanced cervical cancer.

Conditions

Cervical Cancer ≥ FIGO IIB and or Lymph Node Metastases

Keywords

cervical cancer; lymph node metastases; FIGO IIB

Outcome Measures

Primary Outcomes (2)

• Progression free survival (PFS)

  Tumor response assessed by MRI Pelvic according to resist

  From Baseline to 2 years

• The adverse events according to NCI-CTCAE v5.0

  Safety and tolerability (according to NCI-CTCAE v5.0)

  From the time of signed informed consent until 100 days after the last study drug administration

Study Arms (1)

Study medication

EXPERIMENTAL

All eligible patients will receive study medication: * Pre-Chemo-radio-immunotherapy Treatment for two weeks before start of Chemo-radio-immunotherapy * Concurrent Chemo-radio-immunotherapy (week 1-7) * Maintenance Treatment (six months) after Chemo-radio-immunotherapy

Drug: Pre-Chemo-radio-immunotherapy Treatment (Nivolumab/Ipilimumab); Drug: Concurrent Chemo-radio-immunotherapy (Nivolumab/Ipilimumab); Procedure: Maintenance Treatment (Nivolumab/Ipilimumab)

Interventions

Pre-Chemo-radio-immunotherapy Treatment (Nivolumab/Ipilimumab) DRUG

Two weeks before start of Chemo-radio-immunotherapy one administration of Nivolumab 3 mg/kg and Ipilimumab 1 mg/kg IV over 30 minutes, with a 30 minute break between Nivolumab and Ipilimumab.

Study medication

Concurrent Chemo-radio-immunotherapy (Nivolumab/Ipilimumab) DRUG

In week 1-7, standard administration of concurrent Cisplatin mono 40mg/m2 body surface area d1, 8, 15, 22, 29 (Monday of each treatment week) during radiotherapy. Simultaneous application of Nivolumab 3mg/kg week 1, 3, 5, 7 (on Thursday) and Ipilimumab 1mg/kg in week 5 (on Thursday).

Study medication

Maintenance Treatment (Nivolumab/Ipilimumab) PROCEDURE

For six months after Chemo-radio-immunotherapy, Nivolumab 3mg/kg every two weeks x12 (week +2, +4, +6, +8, +10, +12, +14, +16, +18, +20, +22, +24 (twelve applications), each application over 30 minutes and Ipilimumab every six weeks x4 (week +6,+12, +18, +24).

Study medication

Eligibility Criteria

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

You may qualify if:

• Fully-informed written consent.
• Females ≥ 18 years of age
• Histologically confirmed squamous cell, adeno- adenosquamous carcinoma of the cervix uteri. Surgical staging prior to treatement is optional.
• FIGO stage ≥ IIB and/or histologically confirmed pelvic lymph node metastases.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Adequate bone marrow, hepatic and renal function including the following:
• Haemoglobin ≥ 9.0 g/dL, absolute neutrophil count ≥ 1,500 /µL, platelets ≥100,000 /µL;
• Total bilirubin ≤ 1.5 x upper normal limit; (except subjects with Gilbert Syndrome who can have total bilirubin \< 3.0 mg/dL);
• AST (SGOT), ALT (SGPT) ≤ 3 x upper normal limit;
• International normalized ratio (INR) ≤ 1.25;
• Creatinine ≤ 1.5 x upper normal limit OR measured or calculated creatinine clearance (according to Cockcroft-Gault) ≥40 mL/min for participant with creatinine levels \>1.5 × institutional ULN (GFR can also be used in place of creatinine or CrCl)
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial. Women must not be breastfeeding.
• The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
• WOCBP must agree to follow instructions for method(s) of contraception for the treatment time and 5 months after.

You may not qualify if:

• Previous systemic therapy in the first-line setting.
• Patients with neuroendocrine (small cell or large cell) tumors or mixed neuroendocrine histology.
• Patients with histologically confirmed para-aortic lymph node metastases.
• Prior organ allograft or allogeneic bone marrow transplantation.
• Local therapies ongoing or completed \<4 weeks prior to the baseline scan.
• Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
• Prior, systemic anti-cancer chemotherapy, radiotherapy administered \<4 weeks prior to study entry, endocrine- or immunotherapy or use of other investigational agents.
• Major surgery within 4 weeks of starting the study. Patients must have recovered from effects of major surgery.
• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive study drug.
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol.
• Subjects with a history of or current CNS metastases. A scan to confirm the absence of brain metastases is not required. Patients with unknown CNS metastatic status and any clinical signs indicative of CNS metastases are eligible if CNS metastases are excluded using CT and/or MRI scans.
• Pregnant or breast-feeding women.
• Any positive test result for hepatitis B virus (e.g. surface antigen \[HBV sAg, Australia antigen\] positive) or hepatitis C virus (Hepatic C antibody \[anti-HCV\] positive, except if HCV-RNA negative.
• Immunocompromised patients, e.g. patients with positive testing for HIV at screening visit or those under corticoid medication or immunosuppressive drugs (e.g. methotrexate).
• Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll. For any cases of uncertainty, it is recommended that the coordinating investigator be consulted prior to signing informed consent.

Sponsors & Collaborators

• Universitätsklinikum Köln: lead
• ZKS Köln: collaborator

MeSH Terms

Conditions

Lymphatic Metastasis; Uterine Cervical Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; 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

Study Officials

• Simone Marnitz, Prof.

  Department of Radiation Oncology, University Hospital of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Open-label, single-arm, monocenter phase II trial

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: August 17, 2022
• Study Start: November 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 18, 2023

Record last verified: 2023-04