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

Status: Active

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. Immunotherapy with monoclonal antibodies, such as cetuximab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving palbociclib and cetuximab may work better in treating patients with squamous cell carcinoma of the head and neck.

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: disease progression after at least one cycle of prior treatment with cisplatin or carboplatin for incurable disease; prior treatment with cetuximab for incurable disease is not permitted * Arms 2 and 3: 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: Arms 1 and 2: 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 Arm 3: disease must be HPV-related SCCHN (defined as OPSCC or unknown primary presenting with a neck mass that is either p16 positive or HPV in situ hybridization [ISH] or polymerase chain reaction [PCR] positive)
  • Minimum of 14 days elapsed since the end of any prior therapy
  • 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)
  • 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
  • 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 PD 0332991
  • 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 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; Arms 2 and 3 of Phase II: patients with HIV infection and antiretroviral therapy are not excluded

Locations & Contacts

Arkansas

Little Rock
University of Arkansas for Medical Sciences
Status: Active
Contact: Konstantinos Arnaoutakis
Phone: 501-686-8274
Email: karnaoutakis@uams.edu

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Conor E. Steuer
Phone: 404-778-7777

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Contact: Prakash C. Neupane
Phone: 913-588-6029
Email: pneupane@kumc.edu

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Contact: Francis Paul Worden
Phone: 734-647-8902

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Contact: Douglas Ray Adkins
Phone: 314-362-4471
Email: dadkins@wustl.edu

New York

Rochester
University of Rochester
Status: Active
Contact: Ronald John Maggiore
Phone: 585-275-5863

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Contact: Juneko E. Grilley-Olson
Phone: 919-843-7718

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of palbociclib (PD 0332991) 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)

IV. To determine the efficacy of PD 0332991 in combination with cetuximab in incurable cetuximab-resistant HPV-related SCCHN. (Phase II, Arm 3)

SECONDARY OBJECTIVES:

I. To assess the adverse events of PD 0332991 in combination with cetuximab. (Phase I and II, arms 1, 2, and 3)

II. To assess the progression-free survival (PFS) of patients with incurable SCHNN treated with PD 0332991 in combination with cetuximab. (Phase II, arms 1, 2, and 3)

III. To assess the overall survival (OS) of patients with incurable SCHNN treated with PD 0332991 in combination with cetuximab. (Phase II, arms 1, 2, and 3)

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, 2, and 3)

TERTIARY OBJECTIVES:

I. To document changes in p16 expression, Ki-67 (immunohistochemistry [IHC]), phosphorylated (phospho)-Rb (IHC), cyclin D1 (IHC), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL] assay) after cetuximab and PD 0332991. (Phase II, arms 1 and 2)

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). (Phase II, arms 1, 2, and 3)

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, patients with cetuximab-resistant disease are assigned to arm 2, and patients with HPV-related cetuximab-resistant disease are assigned to arm 3.

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.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Douglas Ray Adkins

Trial IDs

Primary ID 201404139
Secondary IDs NCI-2014-01079, 14-X031
Clinicaltrials.gov ID NCT02101034