Clinical trial NCT02499120: Safety And Efficacy Study Of Palbociclib Plus Cetuximab Versus Cetuximab To Treat Head And Neck Cancer
Official title: A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 2 STUDY OF PALBOCICLIB PLUS CETUXIMAB VERSUS CETUXIMAB FOR THE TREATMENT OF HUMAN PAPILLOMAVIRUS-NEGATIVE, CETUXIMAB-NAÏVE PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK AFTER FAILURE OF ONE PRIOR PLATINUM-CONTAINING CHEMOTHERAPY REGIMEN
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Keywords: palbociclib, cetuximab, human papillomavirus, squamous cell carcinoma, head and neck cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-07-15
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the combination of palbociclib with cetuximab is superior to cetuximab in prolonging overall survival in HPV-negative, cetuximab-naive patients with recurrent/metastatic squamous cell carcinoma of the head and neck.


Eligibility criteria: Key Inclusion Criteria:

* Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
* Measurable disease as defined per RECIST v. 1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measureable if disease progression at the treated site after completion of therapy is clearly documented.
* HPV- negative SCCHN tumor as determined per institutional standard (eg, p16 IHC; multiplex nucleic acid sequence based amplification \[NASBA\] or other polymerase chain reaction \[PCR\]-based assays).
* Documented progressive disease according to RECIST v1.1 (Appendix 2) following receipt of at least 2 cycles of one platinum-containing chemotherapy regimen administered for R/M disease (min. 50 mg/m2 for cisplatin, minimum area under the curve \[AUC\] \> 4 for carboplatin).
* Availability of a tumor tissue specimen (ie, archived formalin fixed paraffin embedded tissue \[block preferred, or 15 unstained slides\]), which will be used for centralized, retrospective biomarker analysis. If archived tumor tissue is not available, then a de novo biopsy will be required for patient participation.

Key Exclusion Criteria:

* Prior nasopharyngeal cancer, salivary gland or sinus tumors.
* More than one chemotherapeutic regimen given for R/M disease. Prior treatment with immunotherapy is allowed.
* Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
* Progressive disease within 3 months after completion of curatively intended treatment for locoregionally advanced SCCHN.
* Difficulty swallowing capsules.
* Prior use of cetuximab in the R/M disease treatment setting (except cetuximab during curative radiotherapy)

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline up to primary completion date (PCD) (about 34 months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline up to PCD (about 34 months)
measure: Percentage of Participants With Objective Response (OR)
timeFrame: Baseline up to PCD (about 34 months)
measure: Percentage of Participants With Clinical Benefit Response (CBR)
timeFrame: Baseline up to PCD (about 34 months)
measure: Duration of Response (DR)
timeFrame: Baseline up to PCD (about 34 months)
measure: Number of Participants With Treatment-Emergent Adverse Events(TEAEs)
timeFrame: From the first dose through and including 28 calendar days after the last administration of the study treatment (up to 6.9 years)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: From the Screening (Day -28) through and including 28 calendar days after the last administration of the study treatment (up to 7 years)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
timeFrame: Baseline up to PCD (about 34 months)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)
timeFrame: Baseline up to PCD (about 34 months)
measure: Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)
timeFrame: Screening
measure: Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%
timeFrame: Screening
measure: Trough Plasma Concentration (Ctrough) and Within-participant Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib
timeFrame: Pre-dose of Day 15 in Cycle 1 and Cycle 2
measure: Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab
timeFrame: Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Medical Center - La Jolla (Thornton Hospital)
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: San Diego
country: United States
facility: UC San Diego Medical Center- Hillcrest
state: California
city: Louisville
country: United States
facility: University Medical Center, lnc.:DBA University of Louisville Hospital
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Cincinnati
country: United States
facility: University of Cincinnati Investigational Pharmacy
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: West Chester
country: United States
facility: UC Health Physicians Office South
state: Ohio
city: Nashville
country: United States
facility: Henry Joyce Cancer Clinic
state: Tennessee
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc, Lekarna
city: Praha 8
country: Czechia
facility: Nemocnice Na Bulovce, Centralni laboratore Pavilon c. 8
city: Praha 8
country: Czechia
facility: Nemocnice Na Bulovce, Lekarna, Oddeleni Centralni pripravy
city: Praha 8
country: Czechia
facility: Nemocnice Na Bulovce, Ustav radiacni onkologie
city: Debrecen
country: Hungary
facility: Debreceni Egyetem klinikai Koezpont Onkologiai Intezet
city: Pecs
country: Hungary
facility: Neuro CT Kft
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem, Klinikai Kozpont, Laboratoriumi
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem, Klinikai Kozpont,
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet,Onkologiai Kozpont
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Napoli
city: Nagoya
country: Japan
facility: Aichi cancer center Central hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sapporo
country: Japan
facility: Hokkaido University Hospital/Otolaryngology
state: Hokkaido
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo LEON
city: Oaxaca
country: Mexico
facility: Cirugia y Ginecobstetricia de Oaxaca S.A de C.V Hospital Reforma
state: Oaxaca DE Juarez
city: Oaxaca
country: Mexico
facility: Diaz San Juan Noe, Imagenologia Siglo XXI San Felipe
state: Oaxaca DE Juarez
city: Oaxaca
country: Mexico
facility: Daniel Javier Mendez Lopez Imagen y Diagnostico Medico IDM
state: Oaxaca DE Juarez
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S C
city: Brzozow
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii
city: Lodz
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi Oddzial Chemioterapii
city: Olsztyn
country: Poland
facility: SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Kliniczny Onkologii
city: Cluj-Napoca
country: Romania
facility: SC Medisprof SRL
state: Cluj
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf. Nectarie SRL
state: Dolj
city: Craiova
country: Romania
facility: SC Oncolab SRL
state: Dolj
city: Timisoara
country: Romania
facility: S.C. ONCOCENTER Oncologie Clinica S.R.L.
state: Timis
city: Sibiu
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Sibiu, Clinica Oncologie Medicala
city: Arkhangelsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of Arkhangelsk Region
state: Arkhangelsk Region
city: Sochi
country: Russian Federation
facility: State Budgetary Healthcare Institution "Oncology Center #2" of the Ministry of
state: Krasnodar Region
city: Kazan
country: Russian Federation
facility: State Autonomous Healthcare Institution Republican Clinical Oncology Dispensary of the Ministry
state: Tatarstan Republic
city: Saint-Petersburg
country: Russian Federation
facility: FSBI "National Medical Scientific Centre of Oncology n.a.N.N.Petrov" of the MOH of Russia
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Bratislava
country: Slovakia
facility: Narodny onkologicky ustav
city: Poprad
country: Slovakia
facility: POKO Poprad, s.r.o.
city: Pamplona
country: Spain
facility: Servicio de Oncologia
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital Department of Pathology
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Antonivka
country: Ukraine
facility: Communal Institution of Kherson Regional Council Kherson Regional Oncological Dispensary
state: Kherson Region
city: Chernivtsy
country: Ukraine
facility: Communal Institution "Chernivtsi Regional clinical oncology dispensary",
city: Dnipropetrovsk
country: Ukraine
facility: SI Dnipropetrovsk Medical Academy of MoH of Ukraine, Chair of Oncology and Medical Radiology
city: Dnipropetrovsk
country: Ukraine
facility: CI Dnipropetrovsk City Multifunctional Clinical Hospital #4 of Dnipropetrovsk Regional Council
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Clinical Hospital, Department of microsurgery of otolaryngology organs
city: Kriviy Rig
country: Ukraine
facility: Communal Institution "Krivorizhskiy Oncology Dispensary" of Dnipropetrovsk Regional Council,
city: Kyiv
country: Ukraine
facility: Clinic of SI "Institute of Otolaryngology n.a. Prof. O.S. Kolomyichenka of NAMSU"
city: Vinnytsia
country: Ukraine
facility: Podilskiy Regional Center of Oncology, Chemotherapy Department
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Adkins DR, Lin JC, Sacco A, Ley J, Oppelt P, Vanchenko V, Komashko N, Yen CJ, Wise-Draper T, Lopez-Picazo Gonzalez J, Radulovic S, Shen Q, Thurm H, Martini JF, Hoffman J, Huang X, Melichar B, Tahara M. Palbociclib and cetuximab compared with placebo and cetuximab in platinum-resistant, cetuximab-naive, human papillomavirus-unrelated recurrent or metastatic head and neck squamous cell carcinoma: A double-blind, randomized, phase 2 trial. Oral Oncol. 2021 Apr;115:105192. doi: 10.1016/j.oraloncology.2021.105192. Epub 2021 Feb 8.