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Head and Neck Squamous Cell CarcinomaPhase 2NCT03389477

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

A Phase 2 study testing Palbociclib, Cetuximab and Cisplatin in people with Head and Neck Squamous Cell Carcinoma, run by Washington University School of Medicine at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Palbociclib, Cetuximab and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
27 Apr 2018to 6 Apr 2027
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.
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  • 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.
  • Rb (retinoblastoma) loss: mutation or homozygous deletion described on genomic sequencing report.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Los Tres Paso Trial: Step One - Neoadjuvant Palbociclib Monotherapy, Step Two - Concurrent Chemoradiation Therapy, and Step Three - Adjuvant Palbociclib Monotherapy in Patients With p16INK4a Negative, HPV-Unrelated Head and Neck Squamous Cell Carcinoma

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.

Being tested
Palbociclib, Cetuximab, Cisplatin, Intensity-Modulated Radiation Therapy, Tumor biopsy
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalbociclibDrug

    Also called Ibrance, PD 0332991

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

  • CetuximabDrug

    Also called Erbitux

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

  • CisplatinDrug

    Also called Platinol-AQ, Platinol

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

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT

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

  • Tumor biopsyProcedure or surgery

    • 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.

  • Peripheral blood drawProcedure or surgery

    Baseline and post-treatment

Study groups in NCT03389477
Study groupRoleWhat they receive
Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclibExperimental* 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
Receives: Drug: Palbociclib; Drug: Cisplatin; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Tumor biopsy; Procedure: Peripheral blood draw
Cohort 2: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclibExperimental* 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
Receives: Drug: Palbociclib; Drug: Cetuximab; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Tumor biopsy; Procedure: Peripheral blood draw

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 cycles (56 days)

Secondary outcomes (7)

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

    • Local-regional disease relapse, a binary variable (Yes vs. No). Local-regional disease relapse rate is defined as the proportion of subjects alive who have local-regional progressed disease at 18 months following completion of CRT, stratified by cohorts.
    • Distant metastases, a binary variable (Yes vs. No). Distant metastases rate is defined as the proportion of subjects alive who have distant metastases at 18 months following completion of CRT, stratified by cohorts.

    Measured: Through 18 months after completion of step 2

  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

    -Progression-free survival (PFS), defined as the interval from the start of Step 2 (CRT) to the first documentation of disease progression or death from any cause or the end of follow-up, stratified by cohorts.

    Measured: Through 5 years after completion of step 2

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

    -Progression-free survival (PFS), defined as the days from the start of Step 2 (CRT) to the first documentation of disease progression or death from any cause or the end of follow-up

    Measured: Through 2 years after completion of step 2

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

    -Overall survival (OS), defined as the days from the time of diagnosis to death from any cause or the end of follow-up

    Measured: Through 5 years after completion of step 2

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

    -Overall survival (OS), defined as the days from the time of diagnosis to death from any cause or the end of follow-up

    Measured: Through 2 years after completion of step 2

  6. Change in Genomic Alterations in Tumor Tissue

    Tumor genomic alterations at baseline and at relapse will be compared to assess for potential mechanisms of primary or secondary resistance to palbociclib.

    Measured: At baseline and at time of disease relapse (up to 5 years)

  7. Association Between Baseline Tumor CDKN2A and CCND1 Alterations and Tumor Response to Palbociclib Given Before CRT and Relapse After CRT

    Number of participants with altered versus wild-type at baseline will be compared with response.

    Measured: At baseline and at time of disease relapse (up to 5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2018
  2. Study start27 Apr 2018
  3. Primary completion15 Feb 2022
  4. Study completion6 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03389477
Sponsor's protocol ID
201802162
Status last verified
Mar 2026
First submitted
27 Dec 2017
Last updated
21 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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