Clinical Trials /

Ruxolitinib in Operable Head and Neck Cancer

NCT03153982

Description:

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.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib in Operable Head and Neck Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 16201
  • SECONDARY ID: NCI-2017-02304
  • NCT ID: NCT03153982

Conditions

  • Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
RuxolitinibJakafiHead and neck squamous cell carcinoma

Purpose

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

      Patients will take ruxolitinib twice daily during the pre-operative window for 14-21 days, or
      up to 28 days for delays in planned surgery. Ruxolitinib will be dispensed in 5 mg tablets.
      Participants will either take three tablets (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.

      Dose will be assigned based on participant platelet count at baseline:

        1. Patients with a platelet count of 200,000 or greater will take 20 mg twice daily (four
           5mg tablets in the morning and four 5mg tablets in the evening);

        2. Patients with a platelet count between150,000 and 200,000 will take 15 mg twice daily
           (three 5 mg tablets in the morning and three 5 mg tablets in the evening).
    

Trial Arms

NameTypeDescriptionInterventions
Head and neck squamous cell carcinomaExperimentalParticipants will take 15 mg or 20 mg of ruxolitinib by mouth twice daily for up to 4 weeks during the pre-operative window. 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).
  • Ruxolitinib

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Tumor Size
Time Frame:Over the duration of the study, which is estimated to be approximately 24 months.
Safety Issue:
Description:Measured as a proportional percent (range -100% to +100%) from baseline to day of final dose of ruxolitinib

Secondary Outcome Measures

Measure:Safety- toxicity, surgical complications, and length of hospital stay
Time Frame:Over the duration of the study, which is estimated to be approximately 24 months.
Safety Issue:
Description:Safety will be reported descriptively, including tabulation of toxicities according to NCI CTCAE v.4, surgical complications, and length of hospital stay.
Measure:Ki-67
Time Frame:Over the duration of the study, which is estimated to be approximately 24 months.
Safety Issue:
Description:The Ki-67 proliferative index will be measured in baseline and post-treatment tumor tissue.
Measure:Biomarkers
Time Frame:Over the duration of the study, which is estimated to be approximately 24 months.
Safety Issue:
Description:Biomarkers of ruxolitinib response or resistance will be analyzed for correlations with change in tumor size and change in Ki-67. Biomarkers to be analyzed included baseline activation and/or modulation of additional JAK/STAT3 signaling pathway proteins, baseline Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) overexpression, and Reverse-phase protein array (RPPA).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of California, San Francisco

Trial Keywords

  • HNSCC

Last Updated

November 4, 2019