Head and Neck Squamous Cell CarcinomaEarly Phase 1NCT02593929
Pharmacodynamic Effects and Predictive Biomarkers With Ruxolitinib in Operable Head and Neck Cancer
A Early Phase 1 study testing ruxolitinib in people with Head and Neck Squamous Cell Carcinoma, run by University of Pittsburgh.
Trial summary
This study will 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Jan 2018
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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 undergo research biopsy prior to receiving drug.
- Age ≥ 18 years.
- ECOG performance status 0-2 (See Appendix I).
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (sensitivity ≤ 25IU HCG/L) within 4 weeks prior to registration and will be repeated within 72 hours prior to the start of study drug administration.
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- 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, AST or ALT ≤ 2.5 x ULN.
- Have signed written informed consent
Who cannot join
- 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.
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- 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
- 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, conivaptam, indinavir, itraconazle, 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.
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
About this study
Official title: Pharmacodynamic Effects and Predictive Biomarkers of JAK/STAT Inhibition With Ruxolitinib in Operable Head and Neck Cancer: a Window Trial
This study will 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.
Read the detailed description
In this study, ruxolitinib will be administered for a short period of 2-3 weeks prior to planned surgical resection of HNSCC. The dose will be 20 mg twice daily, the FDA-approved dose in myelofibrosis. The brief treatment duration is within the expected window of time that elapses from initial patient evaluation by a surgeon to performance of surgery. In the phase 0 or window trial model, a paired specimen analysis permits ex vivo evaluation of target modulation and pharmacodynamic changes in downstream or parallel molecular pathways.32 This study design is optimal in order to assess the biochemical and immunomodulatory effects of ruxolitinib on HNSCC. Furthermore, predictive biomarkers can be developed as related to a clinical endpoint or a biochemical, pharmacodynamic endpoint.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- ruxolitinib
- Keywords
- squamous cell carcinoma, head and neck cancer, operable
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ruxolitinibDrug
| Study group | Role | What they receive |
|---|---|---|
| ruxolitinib | Experimental | Ruxolitinib will be taken orally for 14-21 days prior to surgery, every morning and every evening, and will be discontinued after the morning dose on the day of planned surgical resection. Receives: Drug: ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
baseline and/or pharmacodynamic biomarkers of response to ruxolitinib based upon association with change in tumor size
Measured: 14-21 days
Secondary outcomes (4)
preliminary efficacy of neoadjuvant ruxolitinib in patients with operable HNSCC as determined by quantitative ΔTumor size
Measured: 14-21 days
the tolerability of brief neoadjuvant exposure to ruxolitinib as determined by the number of participants with treatment related adverse events as assessed by CTCAE v4.0
Measured: 14-21 days
the effect of ruxolitinib on the tumoral Ki-67 proliferation index
Evaluate the change in the KI-67 proliferation index after exposure to ruxolitinib. Ki-67 immunohistochemistry will be performed with the Dako North America M7240 antibody and scored quantitatively with Aperio computer-assisted digital analysis by the research pathologist. In keeping with international consensus guidelines, at least 5000 tumor cells/specimen will be counted. The percentage of positive tumor cells represents the proliferation index.
Measured: 14-21 days
additional candidate biomarkers of ruxolitinib response or resistance in HNSCC patients as determined by quantitative ΔTumor size
Measured: 14-21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2015 (estimated)
- Study startJan 2017
- Primary completionJan 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02593929
- Sponsor's protocol ID
- UPCI 14-207
- Status last verified
- Jan 2017
- First submitted
- 14 Oct 2015
- Last updated
- 8 Jun 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Effects and Predictive Biomarkers of JAK/STAT Inhibition With Ruxolitinib in Operable Head and Neck Cancer: a Window Trial
- ClinicalTrials.gov ID
- NCT02593929
- Acronym / sponsor ID
- UPCI 14-207
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Keywords
- squamous cell carcinoma, head and neck cancer, operable
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Study start
- Jan 2017
- Primary completion
- Jan 2018 (estimated)
- First posted
- 2 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will 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.
Detailed description
In this study, ruxolitinib will be administered for a short period of 2-3 weeks prior to planned surgical resection of HNSCC. The dose will be 20 mg twice daily, the FDA-approved dose in myelofibrosis. The brief treatment duration is within the expected window of time that elapses from initial patient evaluation by a surgeon to performance of surgery. In the phase 0 or window trial model, a paired specimen analysis permits ex vivo evaluation of target modulation and pharmacodynamic changes in downstream or parallel molecular pathways.32 This study design is optimal in order to assess the biochemical and immunomodulatory effects of ruxolitinib on HNSCC. Furthermore, predictive biomarkers can be developed as related to a clinical endpoint or a biochemical, pharmacodynamic endpoint.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ruxolitinib | Experimental | Drug: ruxolitinibRuxolitinib will be taken orally for 14-21 days prior to surgery, every morning and every evening, and will be discontinued after the morning dose on the day of planned surgical resection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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 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 undergo research biopsy prior to receiving drug.
- Age ≥ 18 years.
- ECOG performance status 0-2 (See Appendix I).
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ruxolitinib | Drug | ruxolitinib |
Primary outcome
baseline and/or pharmacodynamic biomarkers of response to ruxolitinib based upon association with change in tumor size
Time frame: 14-21 days
4 secondary outcomes
preliminary efficacy of neoadjuvant ruxolitinib in patients with operable HNSCC as determined by quantitative ΔTumor size
Time frame: 14-21 days
the tolerability of brief neoadjuvant exposure to ruxolitinib as determined by the number of participants with treatment related adverse events as assessed by CTCAE v4.0
Time frame: 14-21 days
the effect of ruxolitinib on the tumoral Ki-67 proliferation index
Time frame: 14-21 days
additional candidate biomarkers of ruxolitinib response or resistance in HNSCC patients as determined by quantitative ΔTumor size
Time frame: 14-21 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ruxolitinib in people with Head and Neck Squamous Cell Carcinoma, run by University of Pittsburgh.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
baseline and/or pharmacodynamic biomarkers of response to ruxolitinib based upon association with change in tumor size (time frame: 14-21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.