Impact of Ribociclib on Head and Neck Squamous Cell Cancer

NCT03179956 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: HN-089
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Treatment with a CDK4/6 inhibitor, Ribociclib, decreases pRB1 levels in patients with SCCHN of the oral cavity, oropharynx and larynx.

  pre-treatment to post-treatment changes in pRB1 expression levels will be measured

  1-2 months

Secondary Outcomes (4)

• Change in pre-treatment to post-treatment levels of Ki67 in tissue samples from patients

  2-3 months

• Change in pre-treatment to post-treatment levels of ERK1/2 in tissue samples from patients

  2-3 months

• Change in pre-treatment to post-treatment levels of phosphorylated-ERK1/2 in tissue samples from patients

  2-3 months

• Change in pre-treatment to post-treatment levels of p16 in tissue samples from patients

  2-3 months

Study Arms (1)

Ribociclib

EXPERIMENTAL

Drug: Ribociclib

Interventions

Ribociclib DRUG

Treatment with ribociclib \[600mg\] will be from Days 1-14, with surgical resection on Day 14. Labs (CBC, CMP, coagulation parameters) and an ECG will be checked once in a window defined by days 9-12.

Ribociclib

Eligibility Criteria

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

You may qualify if:

• Patient has an oral cavity cancer, HPV negative oropharynx cancer, or larynx cancer that is amenable to surgical resection for curative intent.
• Surgical resection must be the part of their standard treatment for management of SCCHN cancer.
• Patient must have archival tissue and must consent to provide pre-treatment archival tissue.
• Patient has signed the Informed Consent (ICF) prior to any screening procedures and is able to comply with protocol requirements.
• Male or Female patients who are 18 years or older.
• 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.
• 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.

You may not qualify if:

• Patients with known hypersensitivity to ribociclib or similar class of agent.
• 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.
• 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).
• Patients with known history of HIV infection (testing not mandatory).
• 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.).
• 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)

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

ribociclib

Condition Hierarchy (Ancestors)

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

Study Officials

• Jessica Bauman, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: June 7, 2017
• Study Start: April 2, 2018
• Primary Completion: November 12, 2018
• Study Completion: January 10, 2019
• Last Updated: February 25, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)