Immunotherapy by Nivolumab for HIV+ Patients (CHIVA2)

• ClinicalTrials.gov Identifier: NCT03304093
• Recruitment Status: Unknown
• First Posted: October 6, 2017
• Last Update Posted: February 10, 2021
• Sponsor: Intergroupe Francophone de Cancerologie Thoracique
• Collaborator: ANRS, Emerging Infectious Diseases
• Information provided by (Responsible Party): Intergroupe Francophone de Cancerologie Thoracique

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer Metastatic; Non Small Cell Lung Cancer Stage IIIB; HIV/AIDS	Drug: Nivolumab Injection	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Immunotherapy by Nivolumab After Prior Chemotherapy for HIV+ Patients With Advanced Non-small Cell Lung Cancer (NSCLC): IFCT-CHIVA2 Phase IIa Trial
• Actual Study Start Date: October 19, 2017
• Estimated Primary Completion Date: March 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nivolumab; Nivolumab 3mg/kg every 2 weeks	Drug: Nivolumab Injection; Nivolumab 3mg/kg every 2 weeks

Outcome Measures

Primary Outcome Measures :

1. Disease Control Rate [ Time Frame: 8 weeks ]

Secondary Outcome Measures :

1. Progression Free Survival [ Time Frame: 6 months and one year ]
   Time between the date of inclusion and the first date of documented progression or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment.
2. Overall Survival [ Time Frame: 6 months and one year ]
   Time elapsed between the date of inclusion and death. Subjects who did not die will be censored on the last date a subject was known to be alive.
3. Tolerance [ Time Frame: 8 weeks, 6 months and one year ]
   Adverse Events (AEs) grade (NCI-CTC 4.0)
4. Responses rate according to tissue PD-L1 expression [ Time Frame: 8 weeks ]
5. Quality of life measured by LCSS questionnaire [ Time Frame: After 2, 3, 5, 7 and 9 cycles (each cycle is 14 days) ]
6. Duration of response [ Time Frame: 8 weeks, 6 months and one year ]
7. impact on HIV control and immunological, other associated chronic infection susceptible of reactivation and potential occurrence of autoimmunity [ Time Frame: 8 weeks, 6 months and one year ]

Other Outcome Measures:

1. Monitor HIV, CMV, EBV, HBV, HCV, HHV-8-specific T cell responses in PBMC [ Time Frame: Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days) ]
2. Monitor the HIV reservoirs (HIV-DNA) and the residual HIV replication as well as EBV CMV, HBV, HCV, HHV-8 viral load [ Time Frame: Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days) ]
3. Monitor T cell activation/ exhaustion/differentiation and immune check point expression [ Time Frame: Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days) ]
4. Description of gene mutation that appear to be crucial for the response to immunotherapy or for adverse effects of immunotherapy [ Time Frame: Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days) ]
5. Immune monitoring of adverse effects [ Time Frame: Cycle 1, 2, 3, 9, 15, 27, 51 and end of treatment (each cycle is 14 days) ]
6. Describe the tumoral microenvironment of NSCLC before nivolumab exposure (CD4, CD8, CD3 infiltrate, PD-1, PD-L1 expression) [ Time Frame: At enrolment ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Age ≥ 18 years old
2. HIV1 or HIV2, regardless of CD4 cell count
3. HIV Viral load <200 copies/mL
4. Proven histologically and/or cytologically, stage IIIB-IV or metastatic relapse post-surgery non-small cell lung cancer (NSCLC)
5. Disease recurrence or progression during/after at least one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease
6. Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria
7. Performance status (PS) 0, 1 or 2
8. Written informed consent
9. 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
10. Patients must receive appropriate care and treatment for HIV infection including ART when clinically indicated and subjects should be under the care of a physician experienced in HIV management. In case of recent introduction of cART and CD4 levels <50 cells/ml, inclusion will be possible provided subjects had at least 4 weeks of treatment prior to inclusion, to avoid clinical type IRIS (immune inflammatory syndrome reconstitution). All antiretroviral treatments are allowed.
11. 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.
12. Persons deprived of liberty could be eligible because the expected benefice (improvement of disease control rate) justifies the foreseeable risk (adverse reaction of nivolumab).

Exclusion Criteria:

1. Concurrent malignancies requiring active intervention
2. Active Infection
3. Patient with known EGFR activating tumor mutation or known ALK or ROS1 gene rearrangement not treated with the appropriate targeted therapy.
4. 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).
5. 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.
6. 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.
7. 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.
8. 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.
9. The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 3 weeks prior to inclusion;
10. History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of inclusion or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
11. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of inclusion. Intranasal/inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
12. 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.
13. Legally protected adults.

Contacts and Locations

Locations

France

CH d'Avignon

Avignon, France

CH de la Côte Basque

Bayonne, France

CH Cahors

Cahors, France

CH

Colmar, France

CHI Créteil

Créteil, France

Centre Hospitalier - Pneumologie

Le Mans, France, 72000

Hôpital de la Croix Rousse

Lyon, France

AP-HM Hôpital Nord

Marseille, France

Montpellier - CHRU

Montpellier, France, 34295

Montpellier - ICM

Montpellier, France

APHP - Hopital Tenon - Pneumologie

Paris, France, 75020

Paris - APHP Bichat

Paris, France

Paris - Pitié-salpêtrière

Paris, France

CH de Pau

Pau, France

Saint Brieuc - CHG

Saint Brieuc, France, 22000

NHC - Pneumologie

Strasbourg, France, 63000

Suresnes - Hopital Foch

Suresnes, France, 92151

CHU Toulouse - Pneumologie

Toulouse, France

Sponsors and Collaborators

Intergroupe Francophone de Cancerologie Thoracique

ANRS, Emerging Infectious Diseases

Investigators

• Principal Investigator: Armelle LAVOLE, MD; APHP Hôpital Tenon
• Principal Investigator: Jacques CADRANEL, MD, PhD; APHP Hôpital Tenon

More Information

• Responsible Party: Intergroupe Francophone de Cancerologie Thoracique
• ClinicalTrials.gov Identifier: NCT03304093
• Other Study ID Numbers: IFCT-1602
• First Posted: October 6, 2017
• Last Update Posted: February 10, 2021
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Intergroupe Francophone de Cancerologie Thoracique:

IFCT; VIH; Nivolumab; NSCLC

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action