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

NCT03389477 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 201802162
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Tumor Response Rate of Newly Diagnosed p16INK4a Negative, HPV-unrelated HNSCC to Neoadjuvant Palbociclib Monotherapy

  * Tumor response rate is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) based on RECIST criteria * CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). * PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  2 cycles (56 days)

Secondary Outcomes (7)

• Combined Local-regional Disease Relapse Risk and Distant Metastases Risk Following Completion of CRT

  Through 18 months after completion of step 2

• Median Progression-free Survival (PFS) (Stratified by Cohort) of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy

  Through 5 years after completion of step 2

• Progression-free Survival (PFS) of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy

  Through 2 years after completion of step 2

• Median Overall Survival (OS) of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy

  Through 5 years after completion of step 2

• Overall Survival of Patients Treated With the Three Step Sequence of Palbociclib Monotherapy, CRT, and Adjuvant Palbociclib Monotherapy

  Through 2 years after completion of step 2

Study Arms (2)

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

EXPERIMENTAL

* Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles) * Step 2: Cisplatin 100 mg/m\^2 given on Days 1 and 22 with accelerated IMRT 70 Gy to be administered over 6 weeks * Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cisplatin \& IMRT

Drug: Palbociclib; Drug: Cisplatin; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Tumor biopsy; Procedure: Peripheral blood draw

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

EXPERIMENTAL

* Step 1: Neoadjuvant palbociclib monotherapy (125 mg/day, Days 1-21 of a 28-day cycle for two cycles) * Step 2: Cetuximab given one week before RT and then weekly with accelerated IMRT 70 Gy to be administered over 6 weeks * Step 3: Adjuvant palbociclib 125 mg/day, days 1-21 of each 28-day cycle for six cycles. Adjuvant palbociclib will begin 16 to 22 weeks following completion of cetuximab \& IMRT

Drug: Palbociclib; Drug: Cetuximab; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Tumor biopsy; Procedure: Peripheral blood draw

Interventions

Palbociclib DRUG

Palbociclib is an oral drug available as capsules (or as liquid suspension). The capsules should be taken with food

Also known as: Ibrance, PD 0332991

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib; Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Cetuximab DRUG

-Cetuximab must not be administered as an IV push or bolus

Also known as: Erbitux

Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Cisplatin DRUG

-Patients will receive cisplatin via intravenous (IV) infusion over 60 minutes.

Also known as: Platinol-AQ, Platinol

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Intensity-Modulated Radiation Therapy RADIATION

-Once daily fractions Monday through Friday, with one additional fraction of RT administered on (preferably) Fridays

Also known as: IMRT

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib; Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Tumor biopsy PROCEDURE

* 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.

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib; Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Peripheral blood draw PROCEDURE

Baseline and post-treatment

Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib; Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Pfizer: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

palbociclib; Cetuximab; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Douglas Adkins, M.D.
• Organization: Washington University School of Medicine

dadkins@wustl.edu

(314) 362-4471

Study Officials

• Douglas R Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2017
• First Posted: January 3, 2018
• Study Start: April 27, 2018
• Primary Completion: February 15, 2022
• Study Completion (Estimated): April 6, 2027
• Last Updated: April 21, 2026
• Results First Posted: March 9, 2023

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)