Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Palbociclib

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.

Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.

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.

palbociclib

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 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.

Placebo

Pfizer CT.gov Call Center

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.

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

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

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Pfizer

The same event may appear as both an AE and a SAE. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m\^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m\^2 weekly infused over 60 minutes.

Palbociclib + Cetuximab

Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m\^2 initial dose as a 120-minute IV infusion followed by 250 mg/m\^2 weekly infused over 60 minutes.

Placebo + Cetuximab

Total

Age, Continuous

Sex: Female, Male

White

Black

Asian

Other

Race/Ethnicity, Customized

Baseline analysis population included all participants who were randomized.

Pfizer ClinicalTrials.gov Call Center

The analysis population was intent-to-treat (ITT) population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Overall Survival (OS)

Progression Free Survival (PFS)

The analysis population was ITT population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Percentage of Participants With Objective Response (OR)

Percentage of Participants With Clinical Benefit Response (CBR)

DR was only calculated for the subgroup of all ITT participants with an objective tumor response.

Duration of Response (DR)

AEs (all causality)

AEs (treatment-related)

SAEs (all causality)

SAEs (treatment-related)

Grade 3 or 4 AEs (all causality)

Grade 5 AEs (all causality)

Grade 3 or 4 AEs (treatment-related)

Grade 5 AEs (treatment-related)

The analysis population included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Number of Participants With Treatment-Emergent Adverse Events(TEAEs)

The analysis population included all participants with at least 1 observation of the laboratory test while on study treatment or during lag time.

Number of Participants With Laboratory Abnormalities

Global health status / QOL

Functional scale: Physical functioning

Functional scale: Role functioning

Functional scale: Emotional functioning

Functional scale: Cognitive functioning

Functional scale: Social functioning

Symptom scale/item: Fatigue

Symptom scale/item: Nausea and vomiting

Symptom scale/item: Pain

Symptom scale/item: Dyspnoea

Symptom scale/item: Insomnia

Symptom scale/item: Appetite loss

Symptom scale/item: Constipation

Symptom scale/item: Diarrhoea

Symptom scale/item: Financial difficulties

The analysis population included all ITT participants, who had both baseline and at least 1 follow-up patient reported outcome (PRO) assessment before treatment discontinuation.

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

Symptom scale/item: Swallowing

Symptom scale/item: Senses problems

Symptom scale/item: Speech problems

Symptom scale/item: Trouble with social eating

Symptom scale/item: Trouble with social contact

Symptom scale/item: Less sexuality

Symptom scale/item: Teeth

Symptom scale/item: Opening mouth

Symptom scale/item: Dry mouth

Symptom scale/item: Sticky saliva

Symptom scale/item: Coughing

Symptom scale/item: Felt ill

Symptom scale/item: Pain killers

Symptom scale/item: Nutritional supplements

Symptom scale/item: Feeding tube

Symptom scale/item: Weight loss

Symptom scale/item: Weight gain

The analysis population included all ITT participants, who had both baseline and at least 1 follow-up PRO assessment before treatment discontinuation.

Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)

The analysis population included all participants treated with cetuximab in combination with placebo or palbociclib who had at least 1 baseline biomarker assessment.

Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)

Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%

Ctrough Cycle 1 Day 15

Ctrough Cycle 2 Day 15

WPM-Ctrough

The analysis population included all as-treated participants, who were treated with the study treatments and had at least measured plasma concentration for at least 1 analyte (palbociclib and/or cetuximab)

Spots Global Cancer Trial Database for palbociclib, cetuximab, human papillomavirus, squamous cell carcinoma, head and neck cancer