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.
Additional locations may be listed on ClinicalTrials.gov for NCT03389477.
See trial information on ClinicalTrials.gov for a list of participating sites.
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.
III. Determine the association between baseline tumor CDKN2A and CCND1 alterations and tumor response to palbociclib given before CRT and relapse after CRT.
IV. Determine genomic alterations in tumor tissue obtained at disease relapse.
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.
Additionally, patients undergo tumor biopsy, blood sample collection, laryngoscopy, computed tomography (CT) and fludeoxyglucose (FDG) positron emission tomography (PET)/CT throughout the study.
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.
Additionally, patients undergo tumor biopsy, blood sample collection, laryngoscopy, CT and FDG PET/CT throughout the study.
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.
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorDouglas Ray Adkins
