Clinical Trials /

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

NCT02499120

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: A5481044
  • SECONDARY ID: 2015-000515-41
  • SECONDARY ID: PALATINUS
  • NCT ID: NCT02499120

Conditions

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

Interventions

DrugSynonymsArms
palbociclibIBRANCE, PD-0332991Palbociclib plus Cetuximab
CetuximabERBITUXPalbociclib plus Cetuximab
PlaceboPlacebo plus Cetuximab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Palbociclib plus CetuximabExperimentalPalbociclib, 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.
  • palbociclib
  • Cetuximab
Placebo plus CetuximabActive ComparatorPlacebo 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.
  • Cetuximab
  • Placebo

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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Baseline up to primary completion date (PCD) (about 34 months)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Percentage of Participants With Objective Response (OR)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Percentage of Participants With Clinical Benefit Response (CBR)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Duration of Response (DR)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Number of Participants With Treatment-Emergent Adverse Events(TEAEs)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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. Treatment-emergent AEs (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.
Measure:Number of Participants With Laboratory Abnormalities
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)
Time Frame:Baseline up to PCD (about 34 months)
Safety Issue:
Description: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.
Measure:Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)
Time Frame:Screening
Safety Issue:
Description: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 paticipants 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.
Measure:Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%
Time Frame:Screening
Safety Issue:
Description: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.
Measure:Trough Plasma Concentration (Ctrough) and Within-patient Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib
Time Frame:Pre-dose of Day 15 in Cycle 1 and Cycle 2
Safety Issue:
Description: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.
Measure:Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab
Time Frame:Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • palbociclib, cetuximab, human papillomavirus, squamous cell carcinoma, head and neck cancer

Last Updated

September 20, 2019