Ruxolitinib in Operable Head and Neck Cancer

NCT03153982 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16201NCI-2017-02304
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

JAK/STAT inhibition; Biomarkers

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Participants With Treatment-related Adverse Events

  Up to 12 weeks

• Number of Participants With Documented Surgical Complications

  Up to 12 weeks.

• Median Length of Hospital Stay

  Up to 12 weeks

• Median Change in Ki-67 Proliferative Index Value

  Up to 12 weeks

Study Arms (1)

Neoadjuvant Ruxolitinib

EXPERIMENTAL

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

Interventions

Ruxolitinib DRUG

Given orally

Also known as: Jakafi

Neoadjuvant Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• 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).
• Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) site will be included.
• 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.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (See Appendix 1).
• 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.
• 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.
• Adequate hematologic, renal and hepatic function, as defined by:
• Absolute neutrophil count (ANC) ≥ 1,500/ul, platelets ≥ 150,000/ul.
• Creatinine ≤ 1.5 x institutional upper limit of normal (ULN).
• Bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x ULN.
• Have signed written informed consent

You may not qualify if:

• Subjects who fail to meet the above criteria.
• 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.
• 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.
• 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).
• Current active infection requiring systemic antibiotic or antifungal therapy.
• Acute hepatitis or known HIV.
• Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
• New York Heart Association (NYHA) Class III or IV heart disease.
• 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.
• 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
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Incyte Corporation: collaborator

Study Sites (2)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Related Publications (1)

• 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.

  PMID: 35929989 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Study closed earlier than expected due to slow accrual

Results Point of Contact

• Title: WIlliam Ryan, MD
• Organization: University of California, San Francisco

William.Ryan@ucsf.edu

(415) 502-1877

Study Officials

• William Ryan, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: May 15, 2017
• Study Start: June 8, 2018
• Primary Completion: October 18, 2023
• Study Completion: October 18, 2023
• Last Updated: October 30, 2024
• Results First Posted: October 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)