Safety And Efficacy Study Of Palbociclib Plus Cetuximab Versus Cetuximab To Treat Head And Neck Cancer

Squamous Cell Carcinoma of the Head and Neck (SCCHN) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02499120
• Other study ID #: A5481044
• Secondary ID: 2015-000515-41PA
• Status: Completed
• Phase: Phase 2
• Start date: September 10, 2015
• Est. completion date: September 7, 2022

Study information

• Verified date: August 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: September 7, 2022
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Intervention

Drug:
• palbociclib
Palbociclib will be supplied as capsules containing 75 mg, 100 mg, or 125 mg equivalents of palbociclib free base. Administered with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle.
• Cetuximab
Cetuximab injection for IV infusion will be provided in 100 mg/50 mL, single-use vials, and 200 mg/100 mL, single-use vials. In Japan, cetuximab will be provided in 100 mg/20 mL, single-use vials. Administered, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.
• Placebo
Placebo for palbociclib will be indistinguishable from the palbociclib capsules and will be supplied as capsules matching in size and color the various palbociclib formulations. Administered with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle.

Locations

Country	Name	City	State
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Olomouc, Lekarna	Olomouc
Czechia	Nemocnice Na Bulovce, Centralni laboratore Pavilon c. 8	Praha 8
Czechia	Nemocnice Na Bulovce, Lekarna, Oddeleni Centralni pripravy	Praha 8
Czechia	Nemocnice Na Bulovce, Ustav radiacni onkologie	Praha 8
Hungary	Debreceni Egyetem klinikai Koezpont Onkologiai Intezet	Debrecen
Hungary	Neuro CT Kft	Pecs
Hungary	Pecsi Tudomanyegyetem, Klinikai Kozpont,	Pecs
Hungary	Pecsi Tudomanyegyetem, Klinikai Kozpont, Laboratoriumi	Pecs
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet,Onkologiai Kozpont	Szolnok
Italy	Istituto Nazionale Tumori Napoli	Napoli
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Aichi cancer center Central hospital	Nagoya	Aichi
Japan	Hokkaido University Hospital/Otolaryngology	Sapporo	Hokkaido
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Mexico	Instituto Nacional de Cancerologia	Mexico	Distrito Federal
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo LEON
Mexico	Cirugia y Ginecobstetricia de Oaxaca S.A de C.V Hospital Reforma	Oaxaca	Oaxaca DE Juarez
Mexico	Daniel Javier Mendez Lopez Imagen y Diagnostico Medico IDM	Oaxaca	Oaxaca DE Juarez
Mexico	Diaz San Juan Noe, Imagenologia Siglo XXI San Felipe	Oaxaca	Oaxaca DE Juarez
Mexico	Oaxaca Site Management Organization S C	Oaxaca
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza	Brzozow
Poland	Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii	Gdansk
Poland	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi Oddzial Chemioterapii	Lodz
Poland	SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Kliniczny Onkologii	Olsztyn
Romania	SC Medisprof SRL	Cluj-Napoca	Cluj
Romania	Centrul de Oncologie Sf. Nectarie SRL	Craiova	Dolj
Romania	SC Oncolab SRL	Craiova	Dolj
Romania	Spitalul Clinic Judetean de Urgenta Sibiu, Clinica Oncologie Medicala	Sibiu
Romania	S.C. ONCOCENTER Oncologie Clinica S.R.L.	Timisoara	Timis
Russian Federation	State Budgetary Healthcare Institution of Arkhangelsk Region	Arkhangelsk	Arkhangelsk Region
Russian Federation	State Autonomous Healthcare Institution Republican Clinical Oncology Dispensary of the Ministry	Kazan	Tatarstan Republic
Russian Federation	FSBI "National Medical Scientific Centre of Oncology n.a.N.N.Petrov" of the MOH of Russia	Saint-Petersburg
Russian Federation	State Budgetary Healthcare Institution "Oncology Center #2" of the Ministry of	Sochi	Krasnodar Region
Serbia	Institute for Oncology and Radiology of Serbia	Belgrade
Serbia	Military Medical Academy	Belgrade
Slovakia	Narodny onkologicky ustav	Bratislava
Slovakia	POKO Poprad, s.r.o.	Poprad
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Servicio de Oncologia	Pamplona	Navarra
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung City
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Cheng Kung University Hospital Department of Pathology	Tainan
Taiwan	Tri-Service General Hospital	Taipei
Ukraine	Communal Institution of Kherson Regional Council Kherson Regional Oncological Dispensary	Antonivka	Kherson Region
Ukraine	Communal Institution "Chernivtsi Regional clinical oncology dispensary",	Chernivtsy
Ukraine	CI Dnipropetrovsk City Multifunctional Clinical Hospital #4 of Dnipropetrovsk Regional Council	Dnipropetrovsk
Ukraine	SI Dnipropetrovsk Medical Academy of MoH of Ukraine, Chair of Oncology and Medical Radiology	Dnipropetrovsk
Ukraine	Regional Clinical Hospital, Department of microsurgery of otolaryngology organs	Ivano-Frankivsk
Ukraine	Communal Institution "Krivorizhskiy Oncology Dispensary" of Dnipropetrovsk Regional Council,	Kriviy Rig
Ukraine	Clinic of SI "Institute of Otolaryngology n.a. Prof. O.S. Kolomyichenka of NAMSU"	Kyiv
Ukraine	Podilskiy Regional Center of Oncology, Chemotherapy Department	Vinnytsia
United States	University of Cincinnati Investigational Pharmacy	Cincinnati	Ohio
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	UC San Diego Medical Center - La Jolla (Thornton Hospital)	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	University Medical Center, lnc.:DBA University of Louisville Hospital	Louisville	Kentucky
United States	Henry Joyce Cancer Clinic	Nashville	Tennessee
United States	Mayo Clinic	Rochester	Minnesota
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University School of Medicine, Siteman Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center	Saint Peters	Missouri
United States	UC San Diego Medical Center- Hillcrest	San Diego	California
United States	UC Health Physicians Office South	West Chester	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Czechia,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Taiwan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - randomization date +1)/30.4. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization had their OS times be censored at randomization. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.	Baseline up to primary completion date (PCD) (about 34 months)
Secondary	Progression Free Survival (PFS)	PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever was earlier. Estimates of the PFS curves from the Kaplan Meier method were presented.	Baseline up to PCD (about 34 months)
Secondary	Percentage of Participants With Objective Response (OR)	OR was defined as the overall complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Objective response rate was defined as the proportion of participants with best overall response (BOR) of CR or PR relative to all randomized.	Baseline up to PCD (about 34 months)
Secondary	Percentage of Participants With Clinical Benefit Response (CBR)	CBR was defined as the overall CR, PR, or stable disease>=24 weeks according to the RECIST version 1.1. Clinical benefit response rate was defined as the proportion of participants with CR, PR, or stable disease>= 24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline.	Baseline up to PCD (about 34 months)
Secondary	Duration of Response (DR)	DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1]/30.4.	Baseline up to PCD (about 34 months)
Secondary	Number of Participants With Treatment-Emergent Adverse Events(TEAEs)	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. TEAEs were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	From the first dose through and including 28 calendar days after the last administration of the study treatment (up to 6.9 years)
Secondary	Number of Participants With Laboratory Abnormalities	The hematology, chemistry and coagulation tests were included in the laboratory examination. Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes. Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate and hemoglobin A1c (HbA1c). Coagulation evaluation included activated partial thromboplastin time/partial thromboplastin time, international normalized ratio (INR) or prothrombin time.	From the Screening (Day -28) through and including 28 calendar days after the last administration of the study treatment (up to 7 years)
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)	The EORTC QLQ-C30 is a 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global health/quality of life (QOL) subscale, and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation, and the financial impact of cancer). The questionnaire employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. For functional and global QOL scales, higher scores represented a better level of functioning and all scores were converted to a 0 to 100 scale. For symptom oriented scales, a higher score represented more severe symptoms, and all scores were converted to a 0-100 scale. Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.	Baseline up to PCD (about 34 months)
Secondary	Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)	The EORTC QLQ-H&N35 is designed to be used together with the core QLQ-C30. The recall period for the items in the module was "the past week". Items hn1 to hn30 were scored on 4 point Likert type categorical scales ("not at all", "a little", "quite a bit", "very much"). Items hn31 to hn35 had a "no/yes" response format. The scores were transformed into 0 to 100 scales, with a high score implying a high level of symptoms.Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.	Baseline up to PCD (about 34 months)
Secondary	Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)	A central test was defined as the tumor tissue-based p16 IHC test performed at a central laboratory (Ventana). The analysis of concordance between HPV status as assessed by local or central laboratory included the number and percentage of participants with p16 detected or not detected at the central laboratory, given that all local testing must have been negative for HPV in order for the patient to be eligible for the study. Initial analysis of the p16 status was based on the conventional cutoff of 70% p16-positive tumor cells to call out cases that might be considered HPV-positive. P16 expression was scored as positive if strong and diffuse nuclear and cytoplasmic staining was present in at least 70% of the tumor cells.	Screening
Secondary	Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%	Rb expression in the palbociclib and cetuximab treatment group, the relationship of the biomarker (individually) with PFS and OS were explored using graphical methods such as box plots, at baseline. The tumors of participants were Rb-positive, which was defined by Rb IHC with>=1% positive tumor cells.	Screening
Secondary	Trough Plasma Concentration (Ctrough) and Within-participant Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib	Ctrough is steady-state pre-dose concentration, which was observed directly from data. WPM-Ctrough is within-participant mean steady-state pre-dose concentration. For palbociclib, a steady-state trough was to be defined as a pre-dose plasma concentration following at least 7 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 24 hr +/- 2 hr and 24 min post-dose the day prior to PK collection and no more than 1 hr post-dose on the day of PK collection.	Pre-dose of Day 15 in Cycle 1 and Cycle 2
Secondary	Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab	Ctrough is steady-state pre-dose concentration. Cendinf is steady-state end-of-infusion concentration. Ctrough and Cendinf were observed directly from data. WPM-Ctrough and WPM-Cendinf are within-participant mean steady-state pre-dose concentration and end-of-infusion concentration. Acceptance criteria for a steady-state Cendinf was defined as a PK sample that was 1) collected after at least 3 consecutive weeks of cetuximab IV infusions without interruption or prior dose reduction and 2) was collected at the end of cetuximab infusion time +/- 10% of the actual duration of the cetuximab infusion.	Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2

External Links

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