COL Immunotherapy Before Radiochimio + Ipilimumab (COLIBRI)

• ClinicalTrials.gov Identifier: NCT04256213
• Recruitment Status: Active, not recruiting
• First Posted: February 5, 2020
• Last Update Posted: August 6, 2021
• Sponsor: ARCAGY/ GINECO GROUP
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): ARCAGY/ GINECO GROUP

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cervix Cancer	Drug: Nivolumab and Ipilimumab	Not Applicable

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Multicenter, Pilot Study Evaluating Immune Impact and Safety of Nivolumab in Combination With Ipilimumab (Immune Combination) Before Initial RT-CT Treatment for Cervix Cancer.: the French GINECO - COLIBRI Study
• Actual Study Start Date: July 2, 2020
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: February 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nivolumab + Ipilimumab	Drug: 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)

Outcome Measures

Primary Outcome Measures :

1. CD8+/FOXP3+ relative change of lymphocytes from pre to post treatment biopsies [ Time Frame: Baseline, before RT-CT ]

Secondary Outcome Measures :

1. Adverse events [ Time Frame: Up to 100-days after end of treatment or until initiation of alternative cancer therapy ]
   Assessed by CTCAE 4.03
2. Objective Response Rate [ Time Frame: 1week before RT-CT, 4 weeks after RT-CT ]
3. Progression Free Survival [ Time Frame: 1 year ]
4. Overall Survival [ Time Frame: 3 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.)

Contacts and Locations

Locations

France

Centre François Baclesse

Caen, France, 14000

Centre Jean Perrin

Clermont-Ferrand, France, 63011

CHU Dupuytren

Limoges, France, 87000

Centre Léon Bérard

Lyon, France, 69008

Groupe Hospitalier Diaconesses - Croix Saint-Simon

Paris, France, 75020

Institut Curie

Paris, France, 75278

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

Plérin, France, 22190

Institut Jean Godinot

Reims, France, 51726

Institut Claudius Regaud IUCT-O

Toulouse, France, 31059

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, France, 54519

Sponsors and Collaborators

ARCAGY/ GINECO GROUP

Bristol-Myers Squibb

Investigators

• Principal Investigator: Isabelle RAY-COQUARD, MD, PhD; Centre Leon Berard

More Information

• Responsible Party: ARCAGY/ GINECO GROUP
• ClinicalTrials.gov Identifier: NCT04256213
• Other Study ID Numbers: GINECO-CE108b; 2019-002271-34 ( EudraCT Number )
• First Posted: February 5, 2020
• Last Update Posted: August 6, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ARCAGY/ GINECO GROUP:

Cervix cancer; Immune combination

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Nivolumab; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action