Immunotherapy by Nivolumab for HIV+ Patients

NCT03304093 | Completed Phase 2 DMC

• 1 other identifier: IFCT-1602
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 18

Brief Summary

Two Phase III trials showed superiority in terms of efficacy and tolerance of nivolumab in second-line treatment compared to docetaxel in metastatic NSCLC in the general population, so it is important to evaluate this treatment in PLWHIV (Patient Living With HIV) in maximum security conditions, taking into account their specificities and complex underlying immunological status. As NSCLC in PLWHIV is a rare tumour, a phase 2 trial, using DCR (Disease Control Rate) data, would be able to recruit a sufficient number of patients, in a reasonable period of time, to provide a proof of concept of the safety and efficacy of nivolumab in this population. Therefore, we think that an open-label, one arm phase 2 trial, with a rapid accrual, would be currently a crucial approach and a window of opportunity to explore whether nivolumab could find its place in PLWHIV with NSCLC. Such a trial is typically a trial for an academic sponsor, experienced in PLWHIV with NSCLC, which previously showed its ability to recruit patients with such a rare disease as the IFCT did with the IFCT-1001 CHIVA trial, testing carboplatin plus pemetrexed followed by pemetrexed.

Conditions

Non Small Cell Lung Cancer Metastatic; Non Small Cell Lung Cancer Stage IIIB; HIV/AIDS

Keywords

IFCT; VIH; Nivolumab; NSCLC

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  8 weeks

Secondary Outcomes (7)

• Progression Free Survival

  6 months and one year

• Overall Survival

  6 months and one year

• Tolerance

  8 weeks, 6 months and one year

• Responses rate according to tissue PD-L1 expression

  8 weeks

• Quality of life measured by LCSS questionnaire

  After 2, 3, 5, 7 and 9 cycles (each cycle is 14 days)

Other Outcomes (6)

• Monitor HIV, CMV, EBV, HBV, HCV, HHV-8-specific T cell responses in PBMC

  Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days)

• Monitor the HIV reservoirs (HIV-DNA) and the residual HIV replication as well as EBV CMV, HBV, HCV, HHV-8 viral load

  Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days)

• Monitor T cell activation/ exhaustion/differentiation and immune check point expression

  Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days)

Study Arms (1)

Nivolumab

EXPERIMENTAL

Nivolumab 3mg/kg every 2 weeks

Drug: Nivolumab Injection

Interventions

Nivolumab Injection DRUG

Nivolumab 3mg/kg every 2 weeks

Nivolumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• HIV1 or HIV2, regardless of CD4 cell count
• HIV Viral load \<200 copies/mL
• Proven histologically and/or cytologically, stage IIIB-IV or metastatic relapse post-surgery non-small cell lung cancer (NSCLC)
• Disease recurrence or progression during/after at least one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
• Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria
• Performance status (PS) 0, 1 or 2
• Written informed consent
• Patients must have adequate organ function: creatinine clearance \> 40 mL/min (Cockcroft, MDRD or CKD-Epi formula or 24h Urine Calculate creatinine clearance from a 24h urine collection ), neutrophiles count \> 1500/mm3; platelets \> 100 000/mm3 ; hemoglobin \> 9 g/dL; hepatic enzymes \< 3N with total bilirubin ≤ 1.5 × ULN (upper limit of normal) except subjects with documented Gilbert's syndrome (≤ 5 × ULN) or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/dL
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 6 months after the final dose of investigational product; cessation of contraception after this point should be discussed with the referent physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. They must also refrain from egg cell donation for 6 months after the final dose of investigational product. Men receiving nivolumab and who are sexually active with women of childbearing potential will be instructed to adhere to contraception (appendix I) for a period of 31 weeks after the last dose of nivolumab.
• Persons deprived of liberty could be eligible because the expected benefice (improvement of disease control rate) justifies the foreseeable risk (adverse reaction of nivolumab).

You may not qualify if:

• Concurrent malignancies requiring active intervention
• Active Infection
• Patient with known EGFR activating tumor mutation or known ALK or ROS1 gene rearrangement not treated with the appropriate targeted therapy.
• History of immunological events related to HIV: lymphoid interstitial pneumonitis (LIP), non-infectious uveitis, encephalitis and other manifestations of CD8 lymphocyte infiltration syndrome, HIV-associated nephropathy (HIVAN).
• Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Active or history of inflammatory bowel disease (eg, diverticulitis, colitis, Crohn's, coeliac disease or other serious gastrointestinal chronic conditions associated with diarrhea). Note that diverticulosis is permitted.
• Symptomatic cerebral metastasis unless treated by brain radiotherapy which will be completed for at least 15 days before the beginning of the treatment; subjects with carcinomatous meningitis.
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
• Legally protected adults.

Sponsors & Collaborators

• Intergroupe Francophone de Cancerologie Thoracique: lead
• ANRS, Emerging Infectious Diseases: collaborator

Study Sites (18)

CH d'Avignon

Avignon, France

Location

CH de la Côte Basque

Bayonne, France

Location

CH Cahors

Cahors, France

Location

CH

Colmar, France

Location

CHI Créteil

Créteil, France

Location

Centre Hospitalier - Pneumologie

Le Mans, 72000, France

Location

Hôpital de la Croix Rousse

Lyon, France

Location

AP-HM Hôpital Nord

Marseille, France

Location

Montpellier - CHRU

Montpellier, 34295, France

Location

Montpellier - ICM

Montpellier, France

Location

APHP - Hopital Tenon - Pneumologie

Paris, 75020, France

Location

Paris - APHP Bichat

Paris, France

Location

Paris - Pitié-salpêtrière

Paris, France

Location

CH de Pau

Pau, France

Location

Saint Brieuc - CHG

Saint-Brieuc, 22000, France

Location

NHC - Pneumologie

Strasbourg, 63000, France

Location

Suresnes - Hopital Foch

Suresnes, 92151, France

Location

CHU Toulouse - Pneumologie

Toulouse, France

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Acquired Immunodeficiency Syndrome

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System 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

• Armelle LAVOLE, MD

  APHP Hôpital Tenon

  PRINCIPAL INVESTIGATOR

• Jacques CADRANEL, MD, PhD

  APHP Hôpital Tenon

  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

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: October 6, 2017
• Study Start: October 19, 2017
• Primary Completion: February 18, 2021
• Study Completion: February 18, 2022
• Last Updated: May 12, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)