Clinical Trials /

Impact of Ribociclib on Head and Neck Squamous Cell Cancer

NCT03179956

Description:

A window of opportunity study which would allow brief treatment of HPV negative SCCHN with a CDK4/6 inhibitor, in the pre-operative setting, with biomarker analyses of pre and post treatment tissue. Given that the standard treatment for this population is surgical resection, this would not impact or alter standard therapy for this population. The goal will be to learn more about the alterations in pRB1 levels, as well as other signaling markers, in order to be able to eventually plan a biomarker driven treatment study.

Related Conditions:
  • Head and Neck Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Lip and Oral Cavity Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Carcinoma
Recruiting Status:

Terminated

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Impact of Ribociclib on Head and Neck Squamous Cell Cancer
  • Official Title: Biomarker Window of Opportunity Study to Evaluate the Impact of Ribociclib on Head and Neck Squamous Cell Cancer

Clinical Trial IDs

  • ORG STUDY ID: HN-089
  • NCT ID: NCT03179956

Conditions

  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
RibociclibRibociclib

Purpose

A window of opportunity study which would allow brief treatment of HPV negative SCCHN with a CDK4/6 inhibitor, in the pre-operative setting, with biomarker analyses of pre and post treatment tissue. Given that the standard treatment for this population is surgical resection, this would not impact or alter standard therapy for this population. The goal will be to learn more about the alterations in pRB1 levels, as well as other signaling markers, in order to be able to eventually plan a biomarker driven treatment study.

Trial Arms

NameTypeDescriptionInterventions
RibociclibExperimental
  • Ribociclib

Eligibility Criteria

        Inclusion Criteria:

          1. Patient has an oral cavity cancer, HPV negative oropharynx cancer, or larynx cancer
             that is amenable to surgical resection for curative intent.

          2. Surgical resection must be the part of their standard treatment for management of
             SCCHN cancer.

          3. Patient must have archival tissue and must consent to provide pre-treatment archival
             tissue.

          4. Patient has signed the Informed Consent (ICF) prior to any screening procedures and is
             able to comply with protocol requirements.

          5. Male or Female patients who are 18 years or older.

          6. Patients with known central nervous system (CNS) involvement must have clinically
             stable CNS tumor at the time of screening and should not be receiving steroids and/or
             enzyme-inducing anti-epileptic medications for brain metastases.

          7. Patient has adequate bone marrow and organ function as defined by the following
             laboratory values at screening:

               -  Absolute neutrophil count ≥1.5 × 109/L

               -  Platelets ≥100 × 109/L

               -  Hemoglobin ≥9.0 g/dL

               -  Potassium, total calcium (corrected for serum albumin), magnesium, sodium and
                  phosphorus within normal limits for the institution or corrected to within normal
                  limits with supplements before first dose of study medication per protocol
                  guidelines

               -  INR ≤1.5

               -  Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50 mL/min

               -  In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate
                  aminotransferase (AST) <2.5 x ULN. If the patient has liver metastases, ALT and
                  AST <5 x ULN

               -  Total bilirubin < ULN; or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x
                  ULN in patients with well-documented Gilbert's Syndrome.

          8. Standard, triplicate 12-lead ECG with the following parameters (defined as the mean of
             the triplicate ECGs):

               -  QTcF interval at screening <450msec (using Fridericia's correction)

               -  Resting heart rate 50-90 bpm

          9. Women of child bearing potential must agree to use adequate means to prevent pregnancy

         10. Men should either be sterile or must agree not to impregnate a women

        Exclusion Criteria:

          1. Patients with known hypersensitivity to ribociclib or similar class of agent.

          2. Patients with concurrent malignancy which requires active treatment or malignancy
             within 3 years prior to starting study drug with the exception of basal or squamous
             cell carcinoma, or non-melanomatous skin cancer.

          3. Patients with impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drug (e.g., ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
             resection).

          4. Patients with known history of HIV infection (testing not mandatory).

          5. Patients with any other concurrent severe and/or uncontrolled medical condition that,
             in the investigator's judgment, would cause unacceptable safety risks, contraindicate
             patient participation in the clinical study or compromise compliance with the protocol
             (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled
             fungal, bacterial or viral infections, etc.).

          6. Clinically significant, uncontrolled heart disease and/or recent events including any
             of the following:

               -  History of acute coronary syndromes (including myocardial infarction, unstable
                  angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
                  symptomatic pericarditis within 12 months prior to screening

               -  History of documented congestive heart failure (New York Heart Association
                  functional classification III-IV)

               -  Documented cardiomyopathy

               -  Patients with Left Ventricular Ejection Fraction (LVEF) <50% as determined by
                  Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening

               -  History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal
                  arrhythmias, or conduction abnormality, high grade AV block (e.g. bifascicular
                  block, Mobitz type II and third degree AV block) within 12 months of screening

               -  Congenital long QT syndrome or family history of long QT syndrome

               -  Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or
                  hypomagnesemia, history of cardiac failure, or history of clinically
                  significant/symptomatic bradycardia.

               -  Concomitant use of medication(s) with a known risk to prolong the QT interval
                  and/or known to cause Torsades de Pointe that cannot be discontinued (within 5
                  half-lives or 7 days prior to starting study drug) or replaced by safe
                  alternative medication

               -  Inability to determine the QT interval on screening (QTcF, using Fridericia's
                  correction)

               -  Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening

               -  Bradycardia (heart rate <50 at rest), by ECG or pulse, at screening

          7. Patients receiving any of the following medications that cannot be discontinued 7 days
             prior to starting study drug (see Appendix II, Table 1 for details):

               1. Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit
                  hybrids, pummelos, star-fruit, and Seville oranges

               2. That have a narrow therapeutic window and are predominantly metabolized through
                  CYP3A4/5

               3. That have a known risk to prolong the QT interval or induce Torsades de Pointes,
                  herbal preparations/medications, dietary supplements.

          8. Patients receiving or have received systemic corticosteroids ≤ 2 weeks prior to
             starting study drug or who have not fully recovered from side effects of such
             treatment. The following uses of corticosteroids are permitted: single doses, topical
             applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways
             diseases), eye drops or local injections (e.g., intra-articular).

          9. Patients receiving warfarin or other coumadin-derived anticoagulant for treatment,
             prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or
             fondaparinux is allowed.

         10. Patient who has received radiotherapy ≤4 weeks or limited field radiation for
             palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1
             or better from related side effects of such therapy (exceptions include alopecia)
             and/or in whom ≥25% of the bone marrow (Ellis, 1961) was irradiated.

         11. Patient who has had prior treatment for current oral cavity malignancy, except for
             biopsy for diagnostic purposes.

         12. Patient has had major surgery within 14 days prior to starting study drug or has not
             recovered from major side effects (tumor biopsy is not considered as major surgery).

         13. Patient has not recovered from all toxicities due to prior anticancer therapies for a
             different malignancy to NCI-CTCAE version 4.03 Grade ≤1 (Exception to this criterion:
             patients with any grade of alopecia and neuropathy grade≤ 2 are allowed to enter the
             study).

         14. Patient with a Child-Pugh score B or C.

         15. Patient has a history of non-compliance to medical regimen or inability to grant
             consent.

         16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
             female after conception and until the termination of gestation, confirmed by a
             positive hCG laboratory test.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Treatment with a CDK4/6 inhibitor, Ribociclib, decreases pRB1 levels in patients with SCCHN of the oral cavity, oropharynx and larynx.
Time Frame:1-2 months
Safety Issue:
Description:pre-treatment to post-treatment changes in pRB1 expression levels will be measured

Secondary Outcome Measures

Measure:Change in pre-treatment to post-treatment levels of Ki67 in tissue samples from patients
Time Frame:2-3 months
Safety Issue:
Description:
Measure:Change in pre-treatment to post-treatment levels of ERK1/2 in tissue samples from patients
Time Frame:2-3 months
Safety Issue:
Description:
Measure:Change in pre-treatment to post-treatment levels of phosphorylated-ERK1/2 in tissue samples from patients
Time Frame:2-3 months
Safety Issue:
Description:
Measure:Change in pre-treatment to post-treatment levels of p16 in tissue samples from patients
Time Frame:2-3 months
Safety Issue:
Description:

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fox Chase Cancer Center

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