Immunotherapy by Nivolumab After Prior Chemotherapy for HIV+ Patients With Advanced Non-small Cell Lung Cancer (NSCLC): IFCT-CHIVA2 Phase IIa Trial

Intergroupe Francophone de Cancerologie Thoracique18 sites in 1 country30 target enrollmentOctober 19, 2017

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

InterventionsNivolumab Injection

DrugsNivolumab Injection

Overview

Phase: Phase 2
Intervention: Nivolumab Injection
Conditions: Non Small Cell Lung Cancer Metastatic
Sponsor: Intergroupe Francophone de Cancerologie Thoracique
Enrollment: 30
Locations: 18
Primary Endpoint: Disease Control Rate
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 19, 2017

End Date

February 18, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Intergroupe Francophone de Cancerologie Thoracique

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•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.

Exclusion Criteria

•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.
•The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 3 weeks prior to inclusion;
•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.

Arms & Interventions

Nivolumab

Nivolumab 3mg/kg every 2 weeks

Intervention: Nivolumab Injection

Outcomes

Primary Outcomes

Disease Control Rate

Time Frame: 8 weeks

Secondary Outcomes

Quality of life measured by LCSS questionnaire(After 2, 3, 5, 7 and 9 cycles (each cycle is 14 days))
impact on HIV control and immunological, other associated chronic infection susceptible of reactivation and potential occurrence of autoimmunity(8 weeks, 6 months and one year)
Overall Survival(6 months and one year)
Progression Free Survival(6 months and one year)
Responses rate according to tissue PD-L1 expression(8 weeks)
Tolerance(8 weeks, 6 months and one year)
Duration of response(8 weeks, 6 months and one year)