Los Tres Paso: Neoadjuvant Palbociclib Monotherapy, Concurrent Chemoradiation Therapy, Adjuvant Palbociclib Monotherapy in Patients With p16INK4a Negative, HPV-Unrelated Head and Neck Squamous Cell Carcinoma
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Intervention: Palbociclib; Cetuximab; Cisplatin; Intensity-Modulated Radiation Therapy; Tumor biopsy; Peripheral blood draw
Intervention description: Palbociclib is an oral drug available as capsules (or as liquid suspension). The capsules should be taken with food; -Cetuximab must not be administered as an IV push or bolus; -Patients will receive cisplatin via intravenous (IV) infusion over 60 minutes.; -Once daily fractions Monday through Friday, with one additional fraction of RT administered on (preferably) Fridays; Tumor tissue will be collected at baseline and then after two cycles of neoadjuvant palbociclib monotherapy
If the patient has been previously enrolled in Washington University's TAP protocol (head and neck bank, HRPO #201102323), tissue that has been banked may be accessed in lieu of fresh biopsy at baseline.; Baseline and post-treatment
Intervention MeSH terms: Cisplatin; Cetuximab; Palbociclib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the results of treating patients with HPV-unrelated
      head and neck squamous cell carcinoma with neoadjuvant single-agent palbociclib, followed by
      chemoradiation (either cisplatin + IMRT or cetuximab + IMRT depending on patient
      characteristics), followed by adjuvant single-agent palbociclib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Larynx SCC, hypopharynx SCC, or oral cavity SCC. HPV-unrelated OPSCC [defined as
             p16INK4a negative by IHC (staining in < 70% of cells) or HPV High Risk (Type 16 or 18)
             negative by ISH]. P16INK4a 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 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 CT scan, as ≥ 20 mm by
             chest x-ray, or ≥ 10 mm with calipers by clinical exam.

          -  At least 18 years of age.

          -  Normal bone marrow function as defined below:

               -  Absolute neutrophil count ≥ 1,000/mcL

               -  Platelets ≥ 100,000/mcL

               -  Hemoglobin ≥ 9.0 g/dL

          -  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 IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Additional Cohort 1 Eligibility Criteria: Patients enrolling to Cohort 1 must meet all of
        the following criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Adequate organ function defined as:

               -  Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN) and
                  creatinine clearance ≥ 75 mL/min

               -  Bilirubin ≤ 1.5 x IULN

               -  ALT and AST ≤ 2.5 x IULN

        Additional Cohort 2 Eligibility Criteria: Patients enrolling to Cohort 2 must meet at least
        one of the following criteria:

          -  ECOG performance status of 2

          -  Reduced organ function defined as:

               -  Creatinine clearance 30-75 mL/min

               -  Bilirubin 1.5-2 x IULN

               -  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 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.