Clinical Trials Register

Summary
EudraCT Number:	2016-003796-22
Sponsor's Protocol Code Number:	IFCT-1602
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-10-05
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2016-003796-22

A.3

Full title of the trial

Immunotherapy by Nivolumab after prior Chemotherapy for HIV+ patients with Advanced non-small cell lung cancer (NSCLC): IFCT-CHIVA2 phase IIa trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Immunotherapy for HIV+ patients with Advanced lung cancer

A.3.2

Name or abbreviated title of the trial where available

CHIVA2

A.4.1

Sponsor's protocol code number

IFCT-1602

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	IFCT
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	IFCT
B.4.2	Country	France
B.4.1	Name of organisation providing support	BMS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IFCT
B.5.2	Functional name of contact point	Contact
B.5.3	Address:
B.5.3.1	Street Address	10 rue de la Grange-Batelière
B.5.3.2	Town/ city	PARIS
B.5.3.3	Post code	75009
B.5.3.4	Country	France
B.5.6	E-mail	contact@ifct.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Opdivo
D.2.1.1.2	Name of the Marketing Authorisation holder	BMS
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Opdivo
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Nivolumab
D.3.9.3	Other descriptive name	NIVOLUMAB
D.3.9.4	EV Substance Code	SUB122750
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Advanced non small cell lung cancer in VIH+ patient

E.1.1.1

Medical condition in easily understood language

Lung cancer in HIV + patient

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10041068
E.1.2	Term	Small cell lung cancer extensive stage
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10020161
E.1.2	Term	HIV infection
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Efficacy of the anti-PD1 antibody (nivolumab) as measured by DCR.

E.2.2

Secondary objectives of the trial

• tolerance: Adverse Events (AEs) grade (NCI-CTC 4.0),
• impact on HIV control and immunological (CD4, CD8, HIV viral load each evaluation), other associated chronic infection susceptible of reactivation (HHV8, CMV, EBV, tuberculosis) and potential occurrence of autoimmunity (organ specific i.e. thyroiditis, adrenalitis and hypophysitis, or non organ specific)
• duration of response
• Reponses rate according to tissue PD-L1 expression
• progression-free survival
• Overall survival
• Quality of life (LCSS)

E.2.3

Trial contains a sub-study

E.3

Principal 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 (Cockroft, MDRD or CKD-Epi formula or 24h Urine Calculate creatinine clearance from a 24h urine collection ), neutrophiles count > 1500/mm3; platelets > 100 000/mm3 ; hemoglobine > 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.

E.4

Principal exclusion criteria

1. Concurrent malignancies requiring active intervention
2. Active Infection
3. 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).
4. 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.
5. 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.
6. 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.
7. 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.
8. The last dose of prior chemotherapy or radiation therapy (with the exception of palliative radiotherapy) was received less than 3 weeks prior to randomization;
9. History of primary immunodeficiency, history of organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
10. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Intranasal/inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

E.5 End points

E.5.1

Primary end point(s)

Disease control rate

E.5.1.1

Timepoint(s) of evaluation of this end point

8 weeks

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

During all the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The study will be ended one year after the last treatment of the last
patient.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-09-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-02-18

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