Head and Neck Squamous Cell CarcinomaPhase 2NCT01469546
Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer
A Phase 2 study testing Axitinib (AG-013736) in people with Head and Neck Squamous Cell Carcinoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to investigate a new agent Axitinib in the treatment of head and neck cancer. This is a new drug that is given as a pill twice a day to treat cancer. This is one of the new, "smart" drugs. 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?
- Axitinib (AG-013736)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Mar 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 documented squamous cell head and neck cancer with or without metastases, not amenable to curative treatment.
- Presence of measurable disease by CT scan.
- Adequate bone marrow, hepatic, and renal function (including absence of proteinuria, PT (Prothrombin Time) <1.5, WBC (White Blood Cell count)≥ 3x109 cells/ml, ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥ 9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN), AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) within 2.5x institutional upper limits of normal unless there are liver metastases in which case AST and ALT within 5.0 x ULN, serum creatinin clearance ≥ 60 ml/min), urinary protein <2+ by urine dipstick (if dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours), documented within 14 days prior to initiation of Axitinib treatment.
- Age ≥18 years.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
- Life expectancy of ≥12 weeks.
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- No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 30 minutes apart. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
- Willingness and ability to comply with scheduled visits, treatment plans, including willingness to take Axitinib, laboratory tests, and other study procedures.
Who cannot join
- Central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (i.e. carotid artery).
- History of hemoptysis.
- Gastrointestinal abnormalities causing impaired absorption requiring intravenous alimentation, prior surgical procedures affecting absorption including gastric resection, treatment for active peptic ulcer disease in the past 6 months, active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy, malabsorption syndromes.
- Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors of epidermal growth factor (EGF), platelet derived growth factor (PDGF), or fibroblast growth factors (FGF) receptors within 30 days preceding study entrance.
- Current use or anticipated inability to avoid use of drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir , and delavirdine).
- Current use or anticipated inability to avoid use of drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).
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- Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
- A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
- History of a malignancy (other than head and neck cancer) except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years.
- Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
- Patients (male and female) having procreative potential who are not willing or not able to use adequate contraception or practicing abstinence.
- Women who are pregnant or breast-feeding.
- History of prior treatment with more than 2 lines of therapy for metastatic head and neck cancer.
- Patients with history of bleeding diathesis, DVT (deep venous thrombosis) or arterial thromboembolism, current use of therapeutic anticoagulation with oral vitamin K antagonists, factor Xa inhibitors, heparin products, oral direct thrombin inhibitors, or presence of non-healing wounds. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed.
- Patients residing in prison.
- Prior experimental therapy within 30 days of planned start of this trial.
- HIV virus infection irrespective of viral load, treatment status, or CD4 count, or acquired immunodeficiency syndrome (AIDS)-related illness.
- Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
- History of deep vein thrombosis or pulmonary embolism within 6 month of anticipated starting of Axitinib.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
About this study
Official title: Phase II Trial Evaluating Axitinib (AG-013736) In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer
The purpose of this study is to investigate a new agent Axitinib in the treatment of head and neck cancer.
This is a new drug that is given as a pill twice a day to treat cancer. This is one of the new, "smart" drugs. It binds to a protein on the surface of the cancer cell called VEGFR, and this way it slows down the growth of cancer cells and kills them. Head and neck cancer cells are known to carry this protein on their surface. Research in animals and in patients with other kinds of cancer showed that Axitinib can be effective at killing cancer cells, or stopping their growth, by this mechanism. It is generally a safe drug that is given by mouth. The investigators do not know, however, whether Axitinib is effective in head and neck cancer. This research study is being conducted to learn if Axitinib works in head and neck cancer, and also to learn to predict who would benefit from it. Four blood draws will be done to check special blood tests while the subjects are treated with Axitinib. These will be drawn at the same time as your routine labs, and there will not be additional sticks needed. A biopsy of the tumor before and after 1 month of treatment may be obtained to test how the cancer cells are responding to treatment. By testing these blood and tissue samples, the researchers will look at special tests (protein molecules) to try to determine what kind of head and neck patients would best respond to this drug. This is an open-label study, meaning that all subjects are on the active drug and there is no placebo (sugar pill).
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Axitinib (AG-013736)
- Keywords
- Squamous Cell Carcinoma of the Head and Neck
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axitinib (AG-013736)Drug
The subjects will be started on treatment with 5 mg of Axitinib twice a day continuously, with subsequent dose escalation to 7 mg and then 10 mg twice a day in the absence of grade 2 or worse toxicities. This will be followed by clinical and/or radiologic response assessment after 8 weeks and subsequently every 2 months until disease progression (defined per RECIST [Response Evaluation Criteria In Solid Tumors] criteria, or obvious progression on clinical or laryngoscopic/endoscopic exam) or intolerable toxicity (defined as below). During treatment on this protocol, all patients will be evaluated for safety. Correlative biomarker analysis will also be conducted.
| Study group | Role | What they receive |
|---|---|---|
| Axitinib (AG-013736) | Experimental | A prospective, single-institution, single-arm phase II study of Axitinib in patients with unresectable recurrent and metastatic head and neck squamous cell carcinoma who have received no more than two prior lines of systemic therapy for recurrent or metastatic head and neck cancer. Receives: Drug: Axitinib (AG-013736) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Patients Alive and Free of Progression at 6 Months
To determine the 6-months progression-free survival (PFS) rate in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.
Measured: 6 months
Secondary outcomes (3)
Number of Participants Who Achieved Complete Response, Partial Response or Stable Disease
To determine the disease control rate (complete response+partial response+stable disease), in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.
Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) will be used.
Complete Response is defined as the disappearance of all tumor for a period of one month.
Partial Response is defined as a 30% or more decrease in the sum of the longest diameters (LD) of all measured lesions without any evidence of progression of any lesion or the appearance of any new lesion for a period of one month.
Stable Disease is defined as any change in measurable disease which is less than the criteria for partial remission or progression without any evidence of new lesions and persisting for at least 2 evaluations or 2 months.
Measured: 2 years
Number of Patients That Experienced Grade 3 or 4 Toxicities
The number of patients who develop these while on treatment and for 28 days after cessation of axitinib, and graded in severity per CTCAE v. 3.0 and as described in the protocol. According to the CTCAE v. 3.0, grade 3 toxicities are severe and grade 4 toxicities are life-threatening or disabling.
Measured: 28 Days Post Treatment
Median Progression-Free Survival (PFS)Time
To evaluate PFS time in patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) treated with Axitinib.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study startJan 2012
- Primary completionApr 2015
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Francis P Worden, MD, Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469546
- Sponsor's protocol ID
- UMCC 2011.053
- Other IDs
- HUM00051095
- Status last verified
- Jul 2016
- First submitted
- 24 Oct 2011
- Last updated
- 29 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial Evaluating Axitinib (AG-013736) In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer
- ClinicalTrials.gov ID
- NCT01469546
- Acronym / sponsor ID
- UMCC 2011.053
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Keywords
- Squamous Cell Carcinoma of the Head and Neck
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Apr 2015 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 10 Nov 2011 (estimated)
- Results
- Posted 9 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate a new agent Axitinib in the treatment of head and neck cancer.
This is a new drug that is given as a pill twice a day to treat cancer. This is one of the new, "smart" drugs. It binds to a protein on the surface of the cancer cell called VEGFR, and this way it slows down the growth of cancer cells and kills them. Head and neck cancer cells are known to carry this protein on their surface. Research in animals and in patients with other kinds of cancer showed that Axitinib can be effective at killing cancer cells, or stopping their growth, by this mechanism. It is generally a safe drug that is given by mouth. The investigators do not know, however, whether Axitinib is effective in head and neck cancer. This research study is being conducted to learn if Axitinib works in head and neck cancer, and also to learn to predict who would benefit from it. Four blood draws will be done to check special blood tests while the subjects are treated with Axitinib. These will be drawn at the same time as your routine labs, and there will not be additional sticks needed. A biopsy of the tumor before and after 1 month of treatment may be obtained to test how the cancer cells are responding to treatment. By testing these blood and tissue samples, the researchers will look at special tests (protein molecules) to try to determine what kind of head and neck patients would best respond to this drug. This is an open-label study, meaning that all subjects are on the active drug and there is no placebo (sugar pill).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib (AG-013736) | Experimental | Drug: Axitinib (AG-013736)A prospective, single-institution, single-arm phase II study of Axitinib in patients with unresectable recurrent and metastatic head and neck squamous cell carcinoma who have received no more than two prior lines of systemic therapy for recurrent or metastatic head and neck cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically documented squamous cell head and neck cancer with or without metastases, not amenable to curative treatment.
- Presence of measurable disease by CT scan.
- Adequate bone marrow, hepatic, and renal function (including absence of proteinuria, PT (Prothrombin Time) <1.5, WBC (White Blood Cell count)≥ 3x109 cells/ml, ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 cells/mm3, hemoglobin ≥ 9.0 g/dL, concentrations of total serum bilirubin within 1.5 x upper limit of normal (ULN), AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) within 2.5x institutional upper limits of normal unless there are liver metastases in which case AST and ALT within 5.0 x ULN, serum creatinin clearance ≥ 60 ml/min), urinary protein <2+ by urine dipstick (if dipstick is ≥2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours), documented within 14 days prior to initiation of Axitinib treatment.
- Age ≥18 years.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
Key exclusion criteria (20 listed)
- Central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (i.e. carotid artery).
- History of hemoptysis.
- Gastrointestinal abnormalities causing impaired absorption requiring intravenous alimentation, prior surgical procedures affecting absorption including gastric resection, treatment for active peptic ulcer disease in the past 6 months, active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy, malabsorption syndromes.
- Previous treatment with anti-angiogenesis agents including thalidomide, or inhibitors of epidermal growth factor (EGF), platelet derived growth factor (PDGF), or fibroblast growth factors (FGF) receptors within 30 days preceding study entrance.
- Current use or anticipated inability to avoid use of drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir , and delavirdine).
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 |
|---|---|---|
| Axitinib (AG-013736)The subjects will be started on treatment with 5 mg of Axitinib twice a day continuously, with subsequent dose escalation to 7 mg and then 10 mg twice a day in the absence of grade 2 or worse toxicities. This will be followed by clinical and/or radiologic response assessment after 8 weeks and subsequently every 2 months until disease progression (defined per RECIST [Response Evaluation Criteria In Solid Tumors] criteria, or obvious progression on clinical or laryngoscopic/endoscopic exam) or intolerable toxicity (defined as below). During treatment on this protocol, all patients will be evaluated for safety. Correlative biomarker analysis will also be conducted. | Drug | Axitinib (AG-013736) |
Primary outcome
Percentage of Patients Alive and Free of Progression at 6 Months
Time frame: 6 months
To determine the 6-months progression-free survival (PFS) rate in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.
3 secondary outcomes
Number of Participants Who Achieved Complete Response, Partial Response or Stable Disease
Time frame: 2 years
Number of Patients That Experienced Grade 3 or 4 Toxicities
Time frame: 28 Days Post Treatment
Median Progression-Free Survival (PFS)Time
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Francis P Worden, MD principal investigator
University of Michigan Rogel Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Axitinib (AG-013736) in people with Head and Neck Squamous Cell Carcinoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
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 10 inclusion and 20 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: finished, as of the sponsor's last update on 29 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Patients Alive and Free of Progression at 6 Months (time frame: 6 months). 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 29 Aug 2016.