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Palbociclib and Intensity-Modulated Radiation Therapy with Cisplatin or Cetuximab in Treating Patients with Head and Neck Squamous Cell Cancer

Trial Status: Active

This phase II trial studies how well palbociclib and intensity-modulated radiation therapy with cisplatin or cetuximab works in treating patients with head and neck squamous cell cancer. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Intensity-modulation radiation therapy uses varying intensities of radiation beams to kill cancer cells and shrink tumors, thereby reducing the damage to nearby healthy tissue. It is not yet known whether giving palbociclib and intensity-modulated radiation therapy with cisplatin or cetuximab works better at treating head and neck squamous cell cancer.

Inclusion Criteria

  • Larynx squamous cell carcinoma (SCC), hypopharynx SCC, or oral cavity SCC; HPV-unrelated oropharyngeal squamous cell carcinoma (OPSCC) (defined as p16^INK4a negative by immunohistochemistry [IHC] [staining in < 70% of cells] or HPV high risk [type 16 or 18] negative by in situ hybridization [ISH]); P16^INK4a positive larynx SCC, hypopharynx SCC, and oral cavity SCC are eligible given the unknown effect of this on the biology of SCC of these subsites
  • Overall stage III, IVA, or IVB disease per American Joint Committee on Cancer (AJCC) version 7.0
  • 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
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9.0 g/dL
  • Corrected QT (QTc) < 500 msec by Fridericia
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 90 days after completion of treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately
  • 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)
  • ADDITIONAL COHORT 1 ELIGIBILITY CRITERIA
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Serum creatinine =< 1.5 x institutional upper limit of normal (IULN) and creatinine clearance >= 75 mL/min
  • Bilirubin =< 1.5 x IULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x IULN
  • ADDITIONAL COHORT 2 ELIGIBILITY CRITERIA
  • ECOG performance status of 2
  • Creatinine clearance 30-75 mL/min; or bilirubin 1.5-2 x IULN; or ALT and AST 2.5-5 x IULN

Exclusion Criteria

  • Diagnosis of cutaneous, paranasal sinus, salivary, or nasopharynx SCC, or diagnosis of neck nodes with unknown primary
  • Diagnosis of P16/HPV-ISH positive OPSCC
  • Presence of distant metastatic disease
  • Prior systemic therapy for current diagnosis of HNSCC
  • A history of other malignancy =< 2 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or low risk/curatively treated prostate, thyroid, and cervical cancers
  • Currently receiving any other investigational agents
  • Treated within the last 7 days prior to day 1 of protocol therapy with: * Food or drugs that are known to be STRONG CYP3A4 inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (e.g. glucocorticoids, progesterone, rifampin, phenobarbital, St. John’s wort) (moderate CYP3A4 inhibitors/inducers are okay) * Drugs that are known to prolong the QT interval * Drugs that are proton pump inhibitors
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib, cisplatin (for cohort 1), or cetuximab (for cohort 2)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g. hypocalcemia, hypokalemia, hypomagnesemia)
  • History of cirrhosis
  • History of renal or liver transplant
  • 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 contraception during the period of the trial and for at least 90 days after completion of treatment
  • Known human immunodeficiency virus (HIV)-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with palbociclib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Douglas Ray Adkins
Phone: 314-362-4471

PRIMARY OBJECTIVE:

I. Determine the tumor response rate of newly diagnosed p16^INK4a negative, HPV-unrelated head and neck squamous cell carcinoma (HNSCC) to neoadjuvant palbociclib monotherapy given over two cycles.

SECONDARY OBJECTIVES:

I. Determine the combined local-regional disease relapse risk and distant metastases risk at 18 months following completion of chemoradiation (CRT).

II. Determine the median and two-year progression-free survival (PFS) and overall survival (OS) (stratified by cohort) of patients treated with the three step sequence of palbociclib monotherapy, CRT, and adjuvant palbociclib monotherapy.

EXPLORATORY OBJECTIVES:

I. Explore potential pharmacodynamic determinants of tumor response to palbociclib monotherapy using genomic, ribonucleic acid (RNA), and protein expression methods.

II. Explore potential pharmacodynamic determinants of locoregional disease relapse risk and distant metastases risk to palbociclib-based therapy using genomic, RNA, and protein expression methods.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I:

STEP 1: Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

STEP 2: Beginning day 1 of cycle 3, patients receive cisplatin intravenous piggyback (IVPB) over 60 minutes on days 1 and 22 and undergo a total of 36 fractions of intensity-modulated radiation therapy (IMRT) QD every weekday (Monday-Friday), with one additional fraction given once a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

STEP 3: Beginning 16 to 22 weeks after chemoradiation in Step 2, patients receive palbociclib PO QD on days 1-21. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

COHORT II:

STEP 1: Patients receive palbociclib as Cohort I.

STEP 2: Beginning 1 week before IMRT as in Cohort I, patients receive cetuximab IVBP once weekly for 7 weeks in the absence of disease progression or unacceptable toxicity.

STEP 3: Patients receive palbociclib as Cohort I.

After completion of study treatment, patients are followed up at 30-45 days, 8 and 12 months, then every 6 months up to 5 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Douglas Ray Adkins

  • Primary ID 201802162
  • Secondary IDs NCI-2018-00376
  • Clinicaltrials.gov ID NCT03389477