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

Last updated date
Study Location
Washington University School of Medicine
Saint Louis, Missouri, 63110, United States
Contact
(314) 362-4471

FOR MORE INFORMATION

Contact a representative by phone, email, or visiting the study website. Please see the references below:

By phone

Pfizer Clinical Trials Contact Center

(314) 362-4471

By email

Contact

[email protected]

Call Now

Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Head and Neck Squamous Cell Carcinoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

NEED INFO?

Questions about a trial? Call or email to reach a Pfizer Clinical Trial Contact Center Representative

Pfizer Clinical Trials Contact Center

1-800-718-1021

[email protected]

TRY A NEW SEARCH

Search for Clinical Trials by condition, keyword or trial number. Share your location or enter your city or zip code to find studies near you.

Based on your search, you may also be interested in

Head and Neck Squamous Cell CarcinomaA Study of PF-00299804 When Given Through a Feeding Tube in Locally Advanced Head and Neck Squamous Cell Carcinoma
NCT01484847
  1. Toronto, Ontario
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Head and Neck Squamous Cell CarcinomaAvelumab, Cetuximab, and Palbociclib in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
NCT03498378
  1. La Jolla, California
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Head and Neck Squamous Cell Carcinoma
Intervention  ICMJE
  • Drug: Palbociclib
    Palbociclib is an oral drug available as capsules (or as liquid suspension). The capsules should be taken with food
    Other Names:
    • Ibrance
    • PD 0332991
  • Drug: Cetuximab
    -Cetuximab must not be administered as an IV push or bolus
    Other Name: Erbitux
  • Drug: Cisplatin
    -Patients will receive cisplatin via intravenous (IV) infusion over 60 minutes.
    Other Names:
    • Platinol-AQ
    • Platinol
  • Radiation: Intensity-Modulated Radiation Therapy
    -Once daily fractions Monday through Friday, with one additional fraction of RT administered on (preferably) Fridays
    Other Name: IMRT
  • Procedure: Tumor biopsy
    • 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.
  • Procedure: Peripheral blood draw
    Baseline and post-treatment
Study Arms  ICMJE
  • Experimental: Cohort 1: 1: palbociclib, 2: Cisplatin & IMRT, 3: palbociclib
    • 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
    Interventions:
    • Drug: Palbociclib
    • Drug: Cisplatin
    • Radiation: Intensity-Modulated Radiation Therapy
    • Procedure: Tumor biopsy
    • Procedure: Peripheral blood draw
  • Experimental: Cohort 1: 1: palbociclib, 2: Cetuximab & IMRT, 3: palbociclib
    • 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
    Interventions:
    • Drug: Palbociclib
    • Drug: Cetuximab
    • Radiation: Intensity-Modulated Radiation Therapy
    • Procedure: Tumor biopsy
    • Procedure: Peripheral blood draw
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 27, 2017)
29
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2027
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Douglas R Adkins, M.D.(314) 362-4471[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03389477
Other Study ID Numbers  ICMJE 201802162
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Douglas R Adkins, M.D.Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP