Clinical Trials List
Protocol NumberA5481044
NCT Number(ClinicalTrials.gov Identfier)NCT02499120
2016-01-06 - 2019-06-30
Phase II
Terminated6
ICD-10C44.42
Squamous cell carcinoma of skin of scalp and neck
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
-
Trial Applicant
Syneos Health
-
Sponsor
Pfizer Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chun-Hung Hua Division of Otolaryngology
- Ming-Yu Lien Division of Hematology & Oncology
- Ching Yun Hsieh Division of Hematology & Oncology
- 詹日全 Division of Otolaryngology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- 蔡牧宏 Division of Otolaryngology
- Sen-Tien Tsai Division of Otolaryngology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 林正純 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 廖斌志 Division of Hematology & Oncology
- Hsiang-Fong Kao Division of Hematology & Oncology
- HUAI-CHENG HUANG Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 陳建志 Division of Radiation Therapy
- 林柏儒 Division of Radiation Therapy
- YI-CHUN LIU Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
Objectives
Primary Objective:
To demonstrate that the combination of palbociclib with cetuximab is superior to
cetuximab in prolonging OS in HPV-negative, cetuximab-naïve patients with R/M
SCCHN in whom one prior platinum-containing chemotherapy has failed.
Secondary Objectives:
To compare secondary measure of efficacy between the treatment arms;
To compare safety and tolerability between the treatment arms;
To compare Patient-Reported Outcome (PRO) measures between the treatment arms;
To characterize the correlations between baseline biomarker (eg, p16, Rb) expression
in tumor tissue and clinical efficacy in both treatment arms;
To characterize steady state trough concentrations for palbociclib, and trough and
maximum concentrations for cetuximib in patients with R/M SCCHN.
Exploratory Objectives:
To explore the correlations between exposure and tumor response and/or safety
findings (sparse pharmacokinetics [PK]);
To characterize alterations in genes, proteins, and ribonucleic acid (RNAs) relevant to
the cell cycle, drug targets, and tumor sensitivity and or resistance in tumor tissue;
To explore pharmacodynamics (PD) modulation of thymidine kinase (TK) in blood;
To explore the relationship between palbociclib and cetuximab drug exposure vs. TK
activity in blood;
To evaluate circulating nucleic acid (CNA) biomarkers in blood (eg, PIK3CA
mutations).
Test Drug
PD-0332991
Active Ingredient
Palbociclib
Dosage Form
Capsule
Dosage
75, 100, 125
Endpoints
Primary Endpoint:
Overall Survival.
Secondary Endpoints:
Progression-Free Survival (PFS), Objective Response (OR), Duration of Response
(DR), per RECIST v1.1, as assessed by investigator;
Type, incidence, severity (as graded by National Cancer Institute Common
Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03), seriousness
and relationship to study medications of adverse events (AEs) and any laboratory
abnormalities;
PRO endpoints: European Organisation for Research and Treatment of Cancer
Quality of Life Instrument (EORTC-QLQ-C30); European Organisation for Research
and Treatment of Cancer Head and Neck Module 35 (EORTC-QLQ-H&N35);
Tumor tissue biomarkers by immunohistochemistry (IHC; p16 and Rb);
Trough concentrations at steady state for palbociclib; trough and maximum
concentrations for cetuximib.
Exploratory Endpoints:
Tumor tissue molecular biomarkers (eg, by next-generation sequencing [NGS], by
gene expression profiling, by IHC);
Tumor tissue PD biomarkers (eg, pRb, pAKT, pS6 or p4EBP1, pERK, FoxM1);
TK activity in blood;
Selected CNA biomarkers in blood (eg; PIK3CA mutations).
Overall Survival.
Secondary Endpoints:
Progression-Free Survival (PFS), Objective Response (OR), Duration of Response
(DR), per RECIST v1.1, as assessed by investigator;
Type, incidence, severity (as graded by National Cancer Institute Common
Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03), seriousness
and relationship to study medications of adverse events (AEs) and any laboratory
abnormalities;
PRO endpoints: European Organisation for Research and Treatment of Cancer
Quality of Life Instrument (EORTC-QLQ-C30); European Organisation for Research
and Treatment of Cancer Head and Neck Module 35 (EORTC-QLQ-H&N35);
Tumor tissue biomarkers by immunohistochemistry (IHC; p16 and Rb);
Trough concentrations at steady state for palbociclib; trough and maximum
concentrations for cetuximib.
Exploratory Endpoints:
Tumor tissue molecular biomarkers (eg, by next-generation sequencing [NGS], by
gene expression profiling, by IHC);
Tumor tissue PD biomarkers (eg, pRb, pAKT, pS6 or p4EBP1, pERK, FoxM1);
TK activity in blood;
Selected CNA biomarkers in blood (eg; PIK3CA mutations).
Inclution Criteria
Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriate member of the
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
2. Measuarable 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.
3. 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).
4. 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).
5. 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.
6. ECOG performance status (PS) 0 or 1 (Appendix 5).
7. Adequate organ and marrow function defined as follows:
Leukocytes >3,000/mm3
(3.0 x 109
/L);
Absolute Neutrophil count (ANC) 1,200/mm3
(1.2 x 109
/L);
Platelets 75,000/mm3
(75 x 109
/L);
Hemoglobin (Hb) 9 g/dL (90 g/L);
Serum creatinine 1.5 x upper limit of normal (ULN) or estimated creatinine
clearance 40 mL/min as calculated using the method standard for the institution;
Total serum bilirubin 1.5 x ULN (3.0 x ULN if Gilbert’s disease);
Asparate aminotransferase (AST) and/or alanine aminotransferase (ALT) 2 x ULN
(5.0 x ULN if liver metastases present);
Alkaline phosphatase 2.5 x ULN (5.0 x ULN if bone or liver metastases present).
8. Male and female patients of childbearing potential and at risk for pregnancy must agree
to use two highly effective methods of contraception throughout the study and for
6 months after the last dose of cetuximab.
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following
criteria):
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses for
at least 12 consecutive months with no alternative pathological or physiological
cause; status may be confirmed by having a serum follicle stimulating hormone
(FSH) level within the laboratory’s reference range for postmenopausal women.
9. Age 18 years (or 20 years as applicable by local country regulations).
10. Evidence of a personally signed and dated informed consent document indicating that the
patient (or a legally acceptable representative) has been informed of all pertinent aspects
of the study.
11. Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
Patient eligibility should be reviewed and documented by an appropriate member of the
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
2. Measuarable 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.
3. 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).
4. 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).
5. 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.
6. ECOG performance status (PS) 0 or 1 (Appendix 5).
7. Adequate organ and marrow function defined as follows:
Leukocytes >3,000/mm3
(3.0 x 109
/L);
Absolute Neutrophil count (ANC) 1,200/mm3
(1.2 x 109
/L);
Platelets 75,000/mm3
(75 x 109
/L);
Hemoglobin (Hb) 9 g/dL (90 g/L);
Serum creatinine 1.5 x upper limit of normal (ULN) or estimated creatinine
clearance 40 mL/min as calculated using the method standard for the institution;
Total serum bilirubin 1.5 x ULN (3.0 x ULN if Gilbert’s disease);
Asparate aminotransferase (AST) and/or alanine aminotransferase (ALT) 2 x ULN
(5.0 x ULN if liver metastases present);
Alkaline phosphatase 2.5 x ULN (5.0 x ULN if bone or liver metastases present).
8. Male and female patients of childbearing potential and at risk for pregnancy must agree
to use two highly effective methods of contraception throughout the study and for
6 months after the last dose of cetuximab.
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following
criteria):
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses for
at least 12 consecutive months with no alternative pathological or physiological
cause; status may be confirmed by having a serum follicle stimulating hormone
(FSH) level within the laboratory’s reference range for postmenopausal women.
9. Age 18 years (or 20 years as applicable by local country regulations).
10. Evidence of a personally signed and dated informed consent document indicating that the
patient (or a legally acceptable representative) has been informed of all pertinent aspects
of the study.
11. Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
Exclusion Criteria
Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
1. Prior nasopharyngeal cancer, salivary gland or sinus tumors.
2. More than one chemotherapeutic regimen given for R/M disease. Prior treatment with
immunotherapy is allowed.
3. 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.
4. Progressive disease within 3 months after completion of curatively intended treatment for
locoregionally advanced SCCHN.
5. Difficulty swallowing capsules or requirement for a feeding tube.
6. Prior use of cetuximab in the R/M disease treatment setting.
7. Prior treatment with any CDK4/6 or EGFR inhibitor (except cetuximab during curative
radiotherapy).
8. Patients treated within the last 7 days prior to randomization with:
Food or drugs that are known to be strong CYP (cytochrome P-450) 3A4 inhibitors
(ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine,
diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole,
lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir,
saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit or
grapefruit juice);
Drugs that are known to be strong CYP3A4 inducers (ie, carbamazepine, felbamate,
nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and
St. John’s wort);
Drugs that are known to prolong the QT interval (Appendix 6).
9. Major surgery, chemotherapy, radiotherapy, any investigational agents, or other
anti-cancer therapy within 2 weeks before randomization. Patients who received prior
radiotherapy to 25% of bone marrow (Appendix 7) are not eligible independent of when
it was received.
10. Diagnosis of any other malignancy within 3 years prior to randomization, except for
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the
cervix.
11. QTc >480 msec (based on the mean value of the triplicate electrocardiograms (ECGs),
family or personal history of long or short QT syndrome, Brugada syndrome or known
history of QTc prolongation, or Torsade de Pointes.
12. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging
drug (eg, hypocalcemia, hypokalemia, hypomagnesemia.
13. Any of the following within 6 months of randomization: myocardial infarction,
severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE
version 4.03 Grade 2, atrial fibrillation of any grade, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident including transient
ischemic attack, or symptomatic pulmonary embolism.
14. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any
upper gastrointestinal surgery including gastric resection that could impair drug
absorption.
15. Known human immunodeficiency virus infection.
16. Other severe acute or chronic medical or psychiatric condition, including recent (within
the past year) or active suicidal ideation or behavior, or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this
study.
17. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab.
18. Pregnant female subjects; breastfeeding female subjects; male and female subjects of
childbearing potential who are unwilling or unable to use two highly effective methods of
contraception as outlined in this protocol for the duration of the study and for 6 months
after the last dose of cetuximab.
19. Patients who are investigational site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees directly involved in the conduct of the
study.
20. Participation in other studies involving investigational drug(s) (Phases 1-4) within
4 weeks before the current study begins and/or during study participation.
Patients presenting with any of the following will not be included in the study:
1. Prior nasopharyngeal cancer, salivary gland or sinus tumors.
2. More than one chemotherapeutic regimen given for R/M disease. Prior treatment with
immunotherapy is allowed.
3. 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.
4. Progressive disease within 3 months after completion of curatively intended treatment for
locoregionally advanced SCCHN.
5. Difficulty swallowing capsules or requirement for a feeding tube.
6. Prior use of cetuximab in the R/M disease treatment setting.
7. Prior treatment with any CDK4/6 or EGFR inhibitor (except cetuximab during curative
radiotherapy).
8. Patients treated within the last 7 days prior to randomization with:
Food or drugs that are known to be strong CYP (cytochrome P-450) 3A4 inhibitors
(ie, amprenavir, atazanavir, boceprevir, clarithromycin, conivaptan, delavirdine,
diltiazem, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole,
lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir,
saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit or
grapefruit juice);
Drugs that are known to be strong CYP3A4 inducers (ie, carbamazepine, felbamate,
nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentin, and
St. John’s wort);
Drugs that are known to prolong the QT interval (Appendix 6).
9. Major surgery, chemotherapy, radiotherapy, any investigational agents, or other
anti-cancer therapy within 2 weeks before randomization. Patients who received prior
radiotherapy to 25% of bone marrow (Appendix 7) are not eligible independent of when
it was received.
10. Diagnosis of any other malignancy within 3 years prior to randomization, except for
adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the
cervix.
11. QTc >480 msec (based on the mean value of the triplicate electrocardiograms (ECGs),
family or personal history of long or short QT syndrome, Brugada syndrome or known
history of QTc prolongation, or Torsade de Pointes.
12. Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging
drug (eg, hypocalcemia, hypokalemia, hypomagnesemia.
13. Any of the following within 6 months of randomization: myocardial infarction,
severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE
version 4.03 Grade 2, atrial fibrillation of any grade, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident including transient
ischemic attack, or symptomatic pulmonary embolism.
14. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any
upper gastrointestinal surgery including gastric resection that could impair drug
absorption.
15. Known human immunodeficiency virus infection.
16. Other severe acute or chronic medical or psychiatric condition, including recent (within
the past year) or active suicidal ideation or behavior, or laboratory abnormality that may
increase the risk associated with study participation or investigational product
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this
study.
17. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to cetuximab.
18. Pregnant female subjects; breastfeeding female subjects; male and female subjects of
childbearing potential who are unwilling or unable to use two highly effective methods of
contraception as outlined in this protocol for the duration of the study and for 6 months
after the last dose of cetuximab.
19. Patients who are investigational site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees directly involved in the conduct of the
study.
20. Participation in other studies involving investigational drug(s) (Phases 1-4) within
4 weeks before the current study begins and/or during study participation.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
120 participants
