Palbociclib and Cetuximab in Treating Patients with Squamous Cell Carcinoma of the Head and Neck

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase II, Phase ITreatmentActive18 and over201404139
NCI-2014-01079, 14-X031, NCT02101034

Trial Description


This phase I/II trial studies the side effects and best dose of palbociclib when given together with cetuximab and to see how well they work in treating patients with squamous cell carcinoma of the head and neck that has spread to other parts of the body or has returned and cannot be removed by surgery. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways by targeting certain cells. Giving palbociclib and cetuximab may work better in treating patients with squamous cell carcinoma of the head and neck.

Further Study Information


I. To determine the maximum tolerated dose of PD 0332991 (palbociclib) when administered in combination with cetuximab to patients with incurable squamous cell carcinoma of the head and neck (SCCHN). (Phase I)

II. To determine the efficacy of PD 0332991 in combination with cetuximab in incurable platin-resistant human papilloma virus (HPV)-unrelated SCCHN. (Phase II, arm 1)

III. To determine the efficacy of PD 0332991 in combination with cetuximab in incurable cetuximab-resistant HPV-unrelated SCCHN. (Phase II, arm 2)


I. To assess the adverse events of PD 0332991 in combination with cetuximab. (Phase I and II, arms 1 and 2)

II. To assess the progression-free survival (PFS) of patients with incurable HPV-unrelated SCHNN treated with PD 0332991 in combination with cetuximab. (Phase II, arms 1 and 2)

III. To assess the overall survival (OS) of patients with incurable HPV-unrelated SCHNN treated with PD 0332991 in combination with cetuximab. (Phase II, arms 1 and 2)

IV. To assess duration of response/stable disease of patients with incurable HPV-unrelated SCHNN treated with PD 0332991 in combination with cetuximab. (Phase II, arms 1 and 2)


I. To document changes in cyclin-dependent kinase inhibitor 2A (p16) expression, Ki-67 (immunohistochemistry [IHC]), phosphorylated (phospho)-retinoblastoma (Rb) (IHC), cyclin D1 (IHC), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] assay) after cetuximab and PD 0332991. (Phase II)

II. To monitor quality of life as documented by quality of life (QOL) measurements from the Functional Assessment of Cancer Therapy Head and Neck (FACT H&N) and European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30).

OUTLINE: This is a phase I, dose-escalation study of palbociclib followed by a phase II study. In phase II, patients with platin-resistant disease are assigned to arm 1 and patients with cetuximab-resistant disease are assigned to arm 2.

Patients receive palbociclib orally (PO) once daily (QD) on days 1-21 and cetuximab intravenously (IV) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 5 years.

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck

Disease must be considered incurable; incurable is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection)

Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 10 mm with computed tomography (CT) scan, as >= 20 mm by chest x-ray, or >= 10 mm with calipers by clinical exam; (phase I only: patients without measurable disease by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria but with evaluable disease by imaging or physical exam will be eligible as well)

Phase I only: any (or no) prior therapy for metastatic disease is allowed, including cetuximab; if a patient has not received prior standard therapy, s/he must have been offered and refused prior standard therapy

Phase II only:

Arm 1: at least one cycle of prior treatment with cisplatin or carboplatin for incurable disease; prior treatment with cetuximab for incurable disease is not permitted

Arm 2: disease progression after at least one cycle of treatment with cetuximab for incurable disease

Phase II only: at least one line of prior therapy for incurable disease

Phase II only: disease must be determined to be HPV-unrelated; HPV-unrelated SCCHN is defined as either p16-negative oropharyngeal squamous cell carcinoma (OPSCC) or non-OPSCC (larynx, hypopharynx, oral cavity) or p16-negative unknown primary SCC presenting with a level 2 or 3 neck node; p16 will be assessed by IHC; a specimen showing any staining will be considered p16-positive

Minimum of 14 days elapsed since the end of any prior therapy

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Absolute neutrophil count >= 1,500 mm^3

Platelets >= 100,000 mm^3

Hemoglobin > 9 g/dL

Total bilirubin =< 1.5 x institutional upper limit of normal (IULN) except in the case of patients with Gilbert’s disease

Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x IULN for patients without liver metastases and =< 5.0 x IULN for patients with liver metastases

Alkaline phosphatase =< 2.5 x IULN for patients without bone metastases and =< 5.0 x IULN for patients with bone metastases

Serum creatinine =< 1.5 x IULN OR calculated creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

Baseline corrected QT interval (QTc) < 480 ms

Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately

Available archival tumor tissue for the proposed correlative studies

Ability to understand and willingness to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria:

Phase II, arm 1 only: prior treatment with cetuximab

Any condition that impairs the ability to swallow PD 0332991 capsules

Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion)

A history of other malignancy =< 1 year previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or synchronous H&N primaries

Currently receiving any other investigational agents

Patient must not have a history of or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have had previously-treated central nervous system (CNS) metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications (with the exception of Keppra) for 1 month prior to first dose of palbociclib

A history of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991, cetuximab, or other agents used in the study

Treated within the last 7 days prior to day 1 of protocol therapy with:

Food or drugs that are known to be cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John’s wort)

Drugs that are known to prolong the QT interval.

Drugs that are proton pump inhibitors

Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia)

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant and/or breastfeeding; women of childbearing potential must have a negative serum pregnancy test within 28 days of study entry; female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraceptive during the period of the trial and for at least 90 days after completion of treatment; the decision of effective contraception will be based on the judgment of the principal investigator or a designated associate

Phase I and Arm 1 of Phase II: Known human immunodeficiency virus (HIV)-positivity and on combination antiretroviral therapy; Arm 2 of Phase II: patients with HIV infection and antiretroviral therapy are not excluded, as there are no pharmacokinetic tests being performed

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Siteman Cancer Center at Washington University

  • National Cancer Institute
Douglas Ray Adkins, Principal Investigator

Trial Sites


Little Rock

University of Arkansas for Medical Sciences

Konstantinos Arnaoutakis
Ph: 501-686-8274

Konstantinos Arnaoutakis
Principal Investigator


Emory University/Winship Cancer Institute

Conor E. Steuer
Ph: 404-778-7777

Conor E. Steuer
Principal Investigator

Kansas City

University of Kansas Cancer Center

Prakash Neupane
Ph: 913-588-6029

Prakash Neupane
Principal Investigator

Ann Arbor

University of Michigan Comprehensive Cancer Center

Francis Paul Worden
Ph: 734-647-8902

Francis Paul Worden
Principal Investigator

Saint Louis

Saint Louis University Hospital

Yifan Tu
Ph: 314-577-8854

Yifan Tu
Principal Investigator

Siteman Cancer Center at Washington University

Douglas Ray Adkins
Ph: 314-362-4471

Douglas Ray Adkins
Principal Investigator

North Carolina
Chapel Hill

UNC Lineberger Comprehensive Cancer Center

Juneko E. Grilley-Olson
Ph: 919-843-7718

Juneko E. Grilley-Olson
Principal Investigator

Link to the current record.
NLM Identifier NCT02101034

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