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EUCTR2016-000725-39

Study of Nivolumab in Combination With Ipilimumab Compared to the Standard of Care (Extreme Study Regimen) as First Line Treatment in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Datenbasis: WHO (Import vom 15.04.2018)
Geändert: 15.04.2018
Krankheitskategorie:

Health conditions (Datenquelle: WHO)

Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)
MedDRA version: 20.0Level: PTClassification code 10060121Term: Squamous cell carcinoma of head and neckSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04]

Interventions (Datenquelle: WHO)


Product Name: Nivolumab-10 ml vial
Product Code: BMS-936558
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: NIVOLUMAB
CAS Number: 946414-94-4
Current Sponsor code: BMS-936558-01
Other descriptive name: BMS936558
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Ipilimumab-40 ml vial
Product Code: BMS-734016
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202-00-9
Current Sponsor code: BMS-734016
Other descriptive name: BMS734016
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: PARAPLATIN 450 mg/45 mL
Pharmaceutical Form: Solution for injection
INN or Proposed INN: CARBOPLATIN
CAS Number: 41575-94-4
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Cisplatin Neocorp 1 mg/ml (100 mg/ vials)
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Erbitux 5 mg/mL (vial of 100 mL)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CETUXIMAB
CAS Number: 205923-56-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: 5-Fluorouracil-Ebewe, 50 mg/ml, (1g/20 ml)
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: FLUOROURACIL
Other descriptive name: FLUOROURACIL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: Cisplatin-Ebewe
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CISPLATIN
CAS Number: 15663-27-1
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milli

Inclusion/Exclusion Criteria (Datenquelle: WHO)

Inclusion criteria:
a) Histologically confirmed head and neck squamous cell carcinoma
(SCCHN), from any of the following primary sites only: oral cavity,
oropharynx, hypopharynx and larynx.
b) Must have metastatic or recurrent disease that is not amendable to
therapy with curative intent (surgery or radiation therapy with or
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without chemotherapy). Subjects that refuse potentially curative salvage
surgery for recurrent disease are ineligible.
c) No prior treatment with systemic anti-cancer therapy for recurrent or
metastatic SCCHN, unless under all of the following conditions:
i) Prior chemotherapy was given as adjuvant or neoadjuvant or as part
of multimodal treatment for locally advanced disease
ii) These treatments must have been completed > 6 months prior to
enrollment
iii) There is no evidence of disease progression for at least 6 months
after completion of such treatment.
d) ECOG Performance Status of 0-1. (See Appendix 1)
e) Measurable disease by CT or MRI per RECIST 1.1 criteria
f) Documentation of HPV p-16 status is required for SCCHN tumor of the
oropharynx.
g) Documentation of PD-L1 status by IHC performed by the central lab
prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion criteria:
1. Target Disease Exceptions
a) Recurrent or metastatic carcinoma of the nasopharynx, squamous cell
carcinoma of unknown primary, squamous cell carcinoma that originated
from the skin and salivary gland or non-squamous histologies (eg,
mucosal melanoma).
b) Subjects with untreated CNS metastases. Subjects are eligible if CNS
metastases have been adequately treated and have neurologically
returned to baseline (except for residual signs or symptoms related to
the CNS treatment) for at least 2 weeks prior to randomization. In
addition, subjects must be either off corticosteroids, or on a stable or
decreasing dose of =<10 mg daily prednisone (or equivalent) for at least
2 weeks prior to randomization.
c) Subjects with carcinomatous meningitis.
2. Medical History and Concurrent Diseases
a) 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 costimulation
or checkpoint pathways.
b) Prior treatment with cetuximab or EGFR inhibitors in any treatment
setting
c) Subjects with previous malignancies (except non-melanoma skin
cancers, and the following in situ cancers: bladder, gastric, esophageal,
colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a
complete remission was achieved at least 2 years prior to study entry
AND no additional therapy is required during the study period.
i) A second primary squamous cell carcinoma of the head and neck is
allowed if eligibility is based on a recurrent or a metastatic first primary
squamous cell carcinoma of the head and neck.
d) Subjects with an active, known or suspected autoimmune disease.
Participants with type I diabetes mellitus, hypothyroidism only requiring
hormone replacement, skin disorders (such as vitiligo, psoriasis, or
alopecia) not requiring systemic treatment, or conditions not expected
to recur in the absence of an external trigger are permitted to enroll.
e) Subjects with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of randomization.
Inhaled or topical steroids, and adrenal replacement steroid doses > 10
mg daily prednisone equivalent, are permitted in the absence of active
autoimmune disease.
3. Physical and Laboratory Test Findings
a) Any positive test for hepatitis B virus or hepatitis C virus indicating
acute or chronic infection
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b) Known history of testing positive for human immunodeficiency virus
(HIV) or known acquired immunodeficiency syndrome (AIDS).
c) Inadequate hematologic, renal or hepatic function defined by any of
the following screening laboratory values:
i) WBC < 2000/ µl
ii) Neutrophils < 1500/ µl
iii) Platelets < 100 x 1000/µl
iv) Hemoglobin <9.0 g/dL
v) Serum creatinine >1.5 x ULN or creatinine clearance < 50 mL/min
(using the Cockcroft Gault formula). Cisplatin should not be used if
creatinine clearance is lower than 60 mL/min
vi) AST/ALT > 3.0 x ULN (> 5 x ULN if liver metastases)
vii) Total Bilirubin > 1.5 x ULN (except subjects with Gilbert Syndrome
who must have a total bilirubin level >= 3.0 x ULN)

Weitere Angaben zur Studie im WHO-Primärregister

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000725-39

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2016-000725-39

Weitere Informationen zur Studie

Registrationsdatum der Studie

31.08.2016

Einschluss der ersten teilnehmenden Person

05.10.2016

Rekrutierungsstatus

Authorised-recruitment may be ongoing or finished

Wissenschaftlicher Titel (Datenquelle: WHO)

An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination with Ipilimumab versus Extreme Study Regimen (cetuximab + cisplatin/carboplatin + fluorouracil) as First Line Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) - (CheckMate 651: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 651)

Studientyp (Datenquelle: WHO)

Interventional clinical trial of medicinal product

Design der Studie (Datenquelle: WHO)

Controlled: yes
Randomised: yes
Open: yes
Single blind: no
Double blind: no
Parallel group: yes
Cross over: no
Other: no
If controlled, specify comparator, Other Medicinial Product: yes
Placebo: no
Other: no
Number of treatment arms in the trial: 2

Phase (Datenquelle: WHO)

Human pharmacology (Phase I): noTherapeutic exploratory (Phase II): noTherapeutic confirmatory - (Phase III): yesTherapeutic use (Phase IV): no

Primäre Endpunkte (Datenquelle: WHO)

Main Objective: To compare progression free survival (PFS) as determined by independent radiology committee (IRC), and overall survival (OS) of nivolumab combined with ipilimumab to Extreme regimen as first line treatment in subjects with recurrent or metastatic SCCHN.;Secondary Objective: -To compare the objective response rate (ORR), based on BICR, of
nivolumab combined with ipilimumab to that of the EXTREME regimen as
first-line treatment in subjects with recurrent or metastatic SCCHN
-To evaluate the duration of response (DOR) of nivolumab combined
with ipilimumab and of the EXTREME regimen as first-line treatment in
subjects with recurrent or metastatic SCCHN
-To evaluate whether PD-L1 expression is a predictive biomarker for
ORR, PFS, and OS;Primary end point(s): - Overall survival (OS) of nivolumab and ipilimumab versus Extreme
regimen
- Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Formal comparisons of PFS and OS will be conducted at the following
times:
-The PFS analysis will be conducted after at least 528 PFS events have
been observed. This is expected to occur 27 months from start of
randomization.
-The final OS analysis will be conducted after at least 505 deaths have
been observed, which is projected to occur 39 months after the first
subject is randomized. In addition, 2 interim analyses of OS are planned,
the first at the time of the PFS comparison and the second after
approximately 85% of events, which is projected to occur 32 months
into the study.

Sekundäre Endpunkte (Datenquelle: WHO)

Secondary end point(s): - Objective response rate (ORR)
- Duration of response (DOR)
- Evaluate PD-L1 expression as a predictive biomarker for efficacy;Timepoint(s) of evaluation of this end point: -ORR: Coincides with time of formal comparison of OS
-DOR: Earliest time at which either co-primary endpoints are significant
-PDL1 expression: Earliest time at which either co-primary endpoints are
significant

Kontakt für Auskünfte (Datenquelle: WHO)

Bristol-Myers Squibb International Corporation

Studiendurchführungsorte

Durchführungsländer (Datenquelle: WHO)

Australia, Austria, France, Germany, Greece, Ireland, Israel, Italy, Japan, Korea, Mexico, Poland, Republic of, Spain, Switzerland, Taiwan, United Kingdom, United States

Kontakt für weitere Auskünfte zur Studie

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

GCT-SU
Parc de l'Alliance - Avenue de Finlande, 4
Bristol-Myers Squibb International Corporation
clinical.trials@bms.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

GCT-SU
Parc de l'Alliance - Avenue de Finlande, 4
Bristol-Myers Squibb International Corporation
clinical.trials@bms.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Bristol-Myers Squibb International Corporation

Weitere Studienidentifikationsnummern

Secondary ID (Datenquelle: WHO)

CA209-651;NCT02741570;2016-000725-39-ES