Ruxolitinib in Operable Head and Neck Cancer

NCT ID: NCT03153982

Last Updated: 2024-10-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-08
• Study Completion Date: 2023-10-18

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.

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Given orally

Interventions

Ruxolitinib

Given orally

Intervention Type: DRUG

Other Intervention Names

Jakafi

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Ryan, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

University of Arizona Cancer Center

Tucson, Arizona, United States

University of California, San Francisco

San Francisco, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 35929989 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2017-02304

Identifier Type: REGISTRY

Identifier Source: secondary_id

16201

Identifier Type: -

Identifier Source: org_study_id