Ruxolitinib in Operable Head and Neck Cancer

Pharmacodynamic Effects and Predictive Biomarkers of Janus Kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) Inhibition With Ruxolitinib in Operable Head and Neck Cancer: a Window Trial

The purpose of this study is to assess the safety and efficacy of ruxolitinib in patients with operable Head and neck squamous cell carcinoma (HNSCC) who are planned for definitive surgery.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Ruxolitinib

Detailed Description

PRIMARY OBJECTIVES:

I. To identify baseline and/or pharmacodynamic biomarkers of response to ruxolitinib, based upon association with quantitative change in tumor size following 14-21 days of neoadjuvant ruxolitinib in patients with operable HNSCC as determined by quantitative change in Tumor size.

SECONDARY OBJECTIVES:

I. To describe the tolerability of brief neoadjuvant exposure to ruxolitinib II. To assess the effect of ruxolitinib on the tumoral Ki-67 proliferation index III. To evaluate additional candidate biomarkers of ruxolitinib response or resistance in HNSCC patients as determined by quantitative change in Tumor size,

OUTLINE:

Participants will be assigned neoadjuvant ruxolitinib based on participant platelet counts at baseline. Participants with a platelet count of 200,000 or greater will take 20 mg twice daily and participants with a platelet count between 150,000 and 200,000 will take 15 mg twice daily. Participants may continue treatment for up to 4 weeks from the time of study entry to time of planned standard of care surgery for cancer. Participants will be followed up for 12-weeks post-operation.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed, primary or recurrent, head and neck squamous cell carcinoma, including variants. Patients must have at least one measureable lesion in accordance with RECIST 1.1 (tumor diameter ≥ 1 cm; short-axis lymph node diameter ≥ 1.5 cm) OR by caliper measurement (tumor diameter ≥ 1 cm). Any diagnostic pretreatment biopsy sample is acceptable including fine needle aspiration (FNA).
2. Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) site will be included.
3. Surgical resection of head and neck must be planned, either as primary treatment or salvage. Patients must have submitted adequate pretreatment archival or fresh tissue.
4. Age ≥ 18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (See Appendix 1).
6. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (sensitivity ≤ 25 human chorionic gonadotropin (HCG) IU/L) within 4 weeks prior to registration and will be repeated within 72 hours prior to the start of study drug administration.
7. Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 12 weeks after study drug is stopped. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.

8. Adequate hematologic, renal and hepatic function, as defined by:

   1. Absolute neutrophil count (ANC) ≥ 1,500/ul, platelets ≥ 150,000/ul.
   2. Creatinine ≤ 1.5 x institutional upper limit of normal (ULN).
   3. Bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN.
9. Have signed written informed consent

Exclusion Criteria:

1. Subjects who fail to meet the above criteria.
2. Prior therapy for head and neck cancer is allowed, and the number of treatments is not limited. However, any systemic therapy should have been completed at least 30 days prior to study enrollment. Any radiation to the head and neck should have been completed at least 30 days prior to study enrollment. Palliative radiation outside of the head and neck does not require a washout.
3. Pregnancy or breastfeeding. Women (patients or partners of male patients) of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. All WOCBP must have a negative pregnancy test within 4 weeks prior to registration, and this must be repeated within 72 hours prior to first receiving ruxolitinib. If the pregnancy test is positive, the patient must not receive ruxolitinib and must not be enrolled in the study.
4. Any unresolved chronic toxicity ≥ grade 2 from previous anticancer therapy (except alopecia and anemia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
5. Current active infection requiring systemic antibiotic or antifungal therapy.
6. Acute hepatitis or known HIV.
7. Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
8. New York Heart Association (NYHA) Class III or IV heart disease.
9. History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (coumadin). Patients who are treated with low molecular weight heparin or fondaparinux are eligible.
10. History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders (e.g., von Willebrand's disease, diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies, or ongoing or recent (≤ 3 months) significant gastrointestinal bleeding
11. Concomitant Medications, any of the following should be considered for exclusion: Strong CYP3A4 inhibitors: (Patients must discontinue drug 7 days prior to starting ruxolitinib), including but not limited to boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, or voriconazole. In addition, patients will be instructed to avoid grapefruit or grapefruit juice, starfruit, or seville oranges.
12. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Neoadjuvant Ruxolitinib; Participants will take 15 mg or 20 mg of ruxolitinib by mouth twice daily for up to 4 weeks during the pre-operative window for 14-21 days, or up to 28 days for delays in planned surgery. Dose will be assigned based on participant platelet count at baseline. The last dose will be taken the morning of planned surgery. Ruxolitinib will be dispensed in 5 mg tablets. Participants will either take three tables (15 mg) in the morning and evening, or four tablets in the morning and evening (20 mg). Participants will be asked to fill out a drug diary indicating when doses of study drug are taken and any side effects they experience.

Drug: Ruxolitinib; Given orally; Other Names: Jakafi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportional Percent Change in Tumor Size by Group	Measured clinical ruxolitinib response of quantitative change in tumor size measured as a proportional percent (range -100% to +100%) from baseline to day 14-21 by group.	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-related Adverse Events	The number of participants with treatment-related adverse events, defined as definite, probable or possibly related to the study intervention and classified according to NCI CTCAE version 4 will be reported.	Up to 12 weeks
Number of Participants With Documented Surgical Complications	The number of participants with documented surgical complications will be reported.	Up to 12 weeks.
Median Length of Hospital Stay	The median length of hospital stay following the standard of care, surgical procedure will be reported.	Up to 12 weeks
Median Change in Ki-67 Proliferative Index Value	A high Ki-67 proliferation index means many cells are dividing quickly and that the cancer is likely to grow and spread. A Ki-67 proliferation index over 30% is typically considered high. The Ki-67 proliferative index will be measured at baseline and post-treatment tumor tissue.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: William Ryan, MD, University of California, San Francisco

Publications and helpful links

General Publications

• Qureshy Z, Li H, Zeng Y, Rivera J, Cheng N, Peterson CN, Kim MO, Ryan WR, Ha PK, Bauman JE, Wang SJ, Long SR, Johnson DE, Grandis JR. STAT3 Activation as a Predictive Biomarker for Ruxolitinib Response in Head and Neck Cancer. Clin Cancer Res. 2022 Nov 1;28(21):4737-4746. doi: 10.1158/1078-0432.CCR-22-0744.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2018
• Primary Completion (Actual): October 18, 2023
• Study Completion (Actual): October 18, 2023

Study Registration Dates

• First Submitted: May 9, 2017
• First Submitted That Met QC Criteria: May 12, 2017
• First Posted (Actual): May 15, 2017

Study Record Updates

• Last Update Posted (Actual): October 30, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Biomarkers; JAK/STAT inhibition
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
• Other Study ID Numbers: 16201; NCI-2017-02304 (Registry Identifier: Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: Yes