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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

Description:

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.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 201802162
  • NCT ID: NCT03389477

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
PalbociclibIbrance, PD 0332991Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib
CetuximabErbituxCohort 1: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib
CisplatinPlatinol-AQ, PlatinolCohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclibExperimentalStep 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
  • Palbociclib
  • Cisplatin
Cohort 1: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclibExperimentalStep 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
  • Palbociclib
  • Cetuximab

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.

          -  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 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)

               -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor response rate of newly diagnosed p16INK4a negative, HPV-unrelated HNSCC to neoadjuvant palbociclib monotherapy
Time Frame:2 cycles (56 days)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Combined local-regional disease relapse risk and distant metastases risk following completion of CRT
Time Frame:Through 18 months after completion of step 2
Safety Issue:
Description: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.
Measure:Median progression-free survival (PFS) (stratified by cohort) of patients treated with the three step sequence of palbociclib monotherapy, CRT, and adjuvant palbociclib monotherapy
Time Frame:Through 5 years after completion of step 2
Safety Issue:
Description:-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.
Measure:Progression-free survival (PFS) of patients treated with the three step sequence of palbociclib monotherapy, CRT, and adjuvant palbociclib monotherapy
Time Frame:Through 2 years after completion of step 2
Safety Issue:
Description:-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
Measure:Median overall survival (OS) of patients treated with the three step sequence of palbociclib monotherapy, CRT, and adjuvant palbociclib monotherapy
Time Frame:Through 5 years after completion of step 2
Safety Issue:
Description:-Overall survival (OS), defined as the days from the time of diagnosis to death from any cause or the end of follow-up
Measure:Overall survival of patients treated with the three step sequence of palbociclib monotherapy, CRT, and adjuvant palbociclib monotherapy
Time Frame:Through 2 years after completion of step 2
Safety Issue:
Description:-Overall survival (OS), defined as the days from the time of diagnosis to death from any cause or the end of follow-up

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

April 30, 2018