COL Immunotherapy Before Radiochimio + Ipilimumab

NCT ID: NCT04256213

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-02

Study Completion Date

2024-08-04

Brief Summary

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This is a multicenter, single arm pilot study evaluating the biological impact of "Nivolumab + Ipilimumab" in patients with cervical squamous cell carcinoma requiring RT-CT as initial therapy

Detailed Description

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The aim of COLIBRI is to evaluate the evolution of the CD8+/FOXP3+ ratio of lymphocytes in pre- versus post-treatment biopsies in patients treated with a combination of Nivolumab and Ipilimumab in a pilot study, just before starting standard RT-CT.

The study will also assess tolerability, Objective Response Rate, clinical activity and biological (dynamic) changes of the immune micro environment

Conditions

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Cervix Cancer

Keywords

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Cervix cancer Immune combination

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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Nivolumab + Ipilimumab

Group Type EXPERIMENTAL

Nivolumab and Ipilimumab

Intervention Type DRUG

Nivolumab, IV D1C1 and D15C1 (before RT-CT) at 3 mg/kg Every 28 days at 480 mg during 6 months after RT-CT

Ipilimumab, 1 mg/kg, IV D1C1 (before RT-CT)

Interventions

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Nivolumab and Ipilimumab

Nivolumab, IV D1C1 and D15C1 (before RT-CT) at 3 mg/kg Every 28 days at 480 mg during 6 months after RT-CT

Ipilimumab, 1 mg/kg, IV D1C1 (before RT-CT)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Histologically confirmed diagnosis of cervical squamous cell carcinoma stage IB3 to IVA, (FIGO 2018)

* Patients requiring RT-CT therapy as standard of care
* Age ≥18
* Patient accepting to undergo a new cervix biopsy
* Adequate marrow function:

* White blood cell (WBC) \>2000/mm3 (stable off any growth factor within 4 weeks of first study drug administration)
* Neutrophils \>1500/ mm3 (stable off any growth factor within 4 weeks of first study drug administration)
* Platelets \> 100× 103/mm3 (transfusion to achieve this level is not permitted within 2 weeks of first study drug administration)
* Hemoglobin \> 8 g/dL (transfusion to achieve this level is not permitted within 2 weeks of first study drug administration)
* Adequate other organ functions:

* ALT and AST \< 3× institutional ULN
* Total bilirubin \< 1.5× institutional ULN (except subjects with Gilbert's Syndrome who must have normal direct bilirubin)
* Normal thyroid function, subclinical hypothyroidism (thyroid-stimulating hormone \[TSH\] \< 10 mIU/mL) or have controlled hypothyroidism on appropriate thyroid supplementation
* Serum creatinine \< 2× ULN or creatinine clearance (CrCl) \> 40 mL/min (measured using the Cockcroft-Gault formula or the MDRD formula for patients older than 65 years-old
* General Health as evidenced by PS ≤2
* Covered by a medical insurance
* Signed and dated informed consent form prior to any study-specific procedure.
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Women of childbearing potential must have a negative serum or urine pregnancy test For females of reproductive potential: use of highly effective contraception and for at least 5 months after administration of the last dose of nivolumab. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmeno-pausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes, and/or uterus).
* All subjects must consent to allow the acquisition of blood samples, FFPE tumor tissue, either a block or 15 to 20 unstained slides, and fresh tumor for performance of correlative studies.

Exclusion Criteria

* Pregnant or breastfeeding women.
* Patient concurrently using other approved or investigational antineoplastic agents.
* Patient candidate for neo adjuvant CT before RT-CT
* Any contraindication to nivolumab or ipilimumab treatments as per Nivolumab and Ipilimumab Investigator's Brochure
* Prior therapy with an immune checkpoint inhibitor
* Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years.
* Immune-deficient status (patients with HIV, immunosuppressive treatment, haematological malignancies, and previous organ transplantation)
* History of any chronic hepatitis as evidenced by:

* Positive test for hepatitis B surface antigen
* Positive test for qualitative hepatitis C viral load (by polymerase chain reaction \[PCR\])

Note: Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion criterion

* Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:

* Myocardial infarction or stroke/transient ischemic attack within the past 6 months
* Uncontrolled angina within the past 3 months
* History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis)
* Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
* QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation \> 480 msec
* Cardiovascular disease-related requirement for daily supplemental oxygen therapy
* Subjects with known or suspected CNS metastases, untreated CNS metastases, are excluded.

Note: However, subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for at least 2 weeks, and no new or progressive neurological signs and symptoms.

• Patients requiring concomitant treatment with therapeutic doses of anticoagulants will not be eligible for this clinical trial.

Note: Patients treated with low dose of anticoagulants for thrombo-embolic events prophylaxis are allowed.

• Any major surgery within 4 weeks of study drug administration. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study drug.

Note: Pelvic and aortic dissection is not considered as traumatic surgery, and therefore can be performed if clinically indicated.

* Subjects with active, known or suspected autoimmune disease. Note: Subjects with skin disorders (such as vitiligo, psoriasis or alopecia), type I diabetes mellitus, hypothyroidism only requiring hormone replacement or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.

Note: Inhaled or topical steroids, and adrenal replacement doses are permitted in the absence of active autoimmune disease.)
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

ARCAGY/ GINECO GROUP

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Isabelle RAY-COQUARD, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Leon Berard

Locations

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Centre François Baclesse

Caen, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Groupe Hospitalier Diaconesses - Croix Saint-Simon

Paris, , France

Site Status

Institut Curie

Paris, , France

Site Status

Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie, CARIO-HPCA

Plérin, , France

Site Status

Institut Jean Godinot

Reims, , France

Site Status

Institut Claudius Regaud IUCT-O

Toulouse, , France

Site Status

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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France

Other Identifiers

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2019-002271-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GINECO-CE108b

Identifier Type: -

Identifier Source: org_study_id