Expansion Trial for Axitinib In Head And Neck Cancer
Study Details
Study Description
Brief Summary
This study will be a prospective, single-institution, single-arm phase II study of Axitinib in patients with unresectable recurrent and metastatic head and neck squamous cell carcinoma. 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 or intolerable toxicity.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Axitinib Participants will receive 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 |
Drug: Axitinib
|
Outcome Measures
Primary Outcome Measures
- Number of Evaluable Patients Alive at 6 Months [6 Months after treatment initiation]
Evaluable defined as any participant who receives at least one cycle of Axitinib. Number of evaluable patients and percentage of patients alive at 6 months is reported.
Secondary Outcome Measures
- Median Overall Survival Time [Up to approximately 2.5 years]
median will be calculated by Kaplan-Meier method.
- Median Progression Free Survival (PFS) Time [Up to approximately 2.5 years]
Median will be calculated by Kaplan-Meier method.
- Best Overall Response [16 Weeks]
Tabulation of best response measured by Choi. Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progression (PD) at 16 weeks. CR is defined as no new lesions and the disappearance of all lesions. PR is defined as a decrease in size of ≥ 10% or a decrease in tumor density (HU) ≥ 15% on CT (Computerized Tomography), no new lesions and no obvious progression of non-measurable disease
- The Number of Patients That Experience Grade 3 or Worse Toxicities [Duration of treatment and up to 28 days after treatment discontinuation]
Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For any treatment-related toxicity that occurred at any grade with a frequency greater than 10% in the overall study population, grade 3 or worse toxicities are shown here.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically documented squamous cell head and neck cancer with or without metastases, not amenable to curative treatment; or the patient has documented refusal of curative treatment.
-
Presence of measurable disease per protocol.
-
Adequate bone marrow, hepatic, and renal function.
-
Age ≥18 years.
-
ECOG (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death.) performance status of 0-2.
-
Life expectancy of ≥12 weeks.
-
No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 30 minutes apart. 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
-
Willingness and ability to comply with scheduled visits, treatment plans, including willingness to take Axitinib, laboratory tests, and other study procedures.
-
If a curative treatment option in the form of chemoradiation exists in a patient with unresectable disease, this has to be attempted first and must have failed, unless the patient has documented refusal of curative treatment.
Exclusion Criteria:
-
Central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (i.e. carotid artery).
-
Active 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 CYP3A4/5 inhibitors
-
Current use or anticipated inability to avoid use of drugs that are known CYP3A4/5 inducers
-
Active seizure disorder or evidence of untreated or progressive brain metastases, spinal cord compression, or carcinomatous meningitis (Subjects with brain metastases are eligible if they have been treated and there is no CT or MRI evidence for at least 4 weeks after CNS (Central Nervous System) metastasis treatment is complete.).
-
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.
-
Patients with history of bleeding diathesis, 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. HIV testing is not required by this protocol.
-
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.
-
Availability of curative treatment option for the patient's cancer, whether surgery, chemotherapy, radiation, or combination thereof, unless the patient has documented refusal of curative treatment.
-
Increased risk of wound dehiscence or presence of non-healing wounds.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- University of Michigan Rogel Cancer Center
- National Comprehensive Cancer Network
Investigators
- Principal Investigator: Paul Swiecicki, M.D., University of Michigan Rogel Cancer Center
Study Documents (Full-Text)
More Information
Publications
None provided.- UMCC 2016.040
- HUM00114022
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | 1 patient enrolled but progressed before starting study treatment. |
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Period Title: Overall Study | |
STARTED | 28 |
COMPLETED | 28 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Overall Participants | 28 |
Age (years) [Mean (Full Range) ] | |
Mean (Full Range) [years] |
63.9
|
Sex: Female, Male (Count of Participants) | |
Female |
3
10.7%
|
Male |
25
89.3%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
1
3.6%
|
White |
27
96.4%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (Count of Participants) | |
United States |
28
100%
|
ECOG performance status (Count of Participants) | |
0 (fully functional) |
11
39.3%
|
1 (minor impairment) |
17
60.7%
|
Disease primary site (Count of Participants) | |
Oral cavity |
2
7.1%
|
Oropharynx |
13
46.4%
|
Larynx |
4
14.3%
|
Nasopharynx |
3
10.7%
|
Cutaneous |
6
21.4%
|
HPV status (Count of Participants) | |
Positive |
10
35.7%
|
Negative |
17
60.7%
|
Unknown |
1
3.6%
|
Previous lines of therapy (Count of Participants) | |
0 |
11
39.3%
|
1 |
6
21.4%
|
2 |
5
17.9%
|
>=3 |
6
21.4%
|
Previous exposure to platinum (Count of Participants) | |
Sensitive |
11
39.3%
|
Refractory |
17
60.7%
|
Previous exposure to PD-1 inhibitor (Count of Participants) | |
Primary resistant |
3
10.7%
|
Acquired resistance |
8
28.6%
|
Outcome Measures
Title | Number of Evaluable Patients Alive at 6 Months |
---|---|
Description | Evaluable defined as any participant who receives at least one cycle of Axitinib. Number of evaluable patients and percentage of patients alive at 6 months is reported. |
Time Frame | 6 Months after treatment initiation |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Measure Participants | 28 |
Number (95% Confidence Interval) [percentage of participants] |
71
253.6%
|
Title | Median Overall Survival Time |
---|---|
Description | median will be calculated by Kaplan-Meier method. |
Time Frame | Up to approximately 2.5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Measure Participants | 28 |
Median (95% Confidence Interval) [months] |
9.8
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Axitinib |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median overall survival time (months) |
Estimated Value | 9.8 | |
Confidence Interval |
(2-Sided) 95% to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Median calculated by Kaplan-Meier method. |
Title | Median Progression Free Survival (PFS) Time |
---|---|
Description | Median will be calculated by Kaplan-Meier method. |
Time Frame | Up to approximately 2.5 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Measure Participants | 28 |
Median (95% Confidence Interval) [months] |
3.5
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Axitinib |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median PFS time (months) |
Estimated Value | 3.5 | |
Confidence Interval |
(2-Sided) 95% to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Median calculated by Kaplan-Meier method. |
Title | Best Overall Response |
---|---|
Description | Tabulation of best response measured by Choi. Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progression (PD) at 16 weeks. CR is defined as no new lesions and the disappearance of all lesions. PR is defined as a decrease in size of ≥ 10% or a decrease in tumor density (HU) ≥ 15% on CT (Computerized Tomography), no new lesions and no obvious progression of non-measurable disease |
Time Frame | 16 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Measure Participants | 28 |
Progressive disease |
10
35.7%
|
Stable disease |
3
10.7%
|
Partial response |
11
39.3%
|
Complete response |
1
3.6%
|
Off treatment before 8-wk scan |
3
10.7%
|
Title | The Number of Patients That Experience Grade 3 or Worse Toxicities |
---|---|
Description | Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For any treatment-related toxicity that occurred at any grade with a frequency greater than 10% in the overall study population, grade 3 or worse toxicities are shown here. |
Time Frame | Duration of treatment and up to 28 days after treatment discontinuation |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Axitinib |
---|---|
Arm/Group Description | Participants will receive 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 |
Measure Participants | 28 |
Fatigue |
6
21.4%
|
Hypertension |
2
7.1%
|
Oral mucositis |
2
7.1%
|
Diarrhea |
1
3.6%
|
Oral pain |
1
3.6%
|
Bleeding |
1
3.6%
|
Adverse Events
Time Frame | AEs were collected from time of initial study treatment administration through death or 28 days after treatment discontinuation. Median treatment duration was three 28-day cycles (range 1-9 cycles). All-cause mortality data was collected from time of initial study treatment administration through death or up to 36 months after treatment discontinuation. Median follow-up was 18 months (range 1-36). | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Axitinib | |
Arm/Group Description | Participants will receive 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 | |
All Cause Mortality |
||
Axitinib | ||
Affected / at Risk (%) | # Events | |
Total | 20/28 (71.4%) | |
Serious Adverse Events |
||
Axitinib | ||
Affected / at Risk (%) | # Events | |
Total | 8/28 (28.6%) | |
Cardiac disorders | ||
Cardiac arrest | 1/28 (3.6%) | 1 |
Gastrointestinal disorders | ||
Abdominal pain | 1/28 (3.6%) | 1 |
Diarrhea | 2/28 (7.1%) | 2 |
Hepatobiliary disorders | ||
Cholecystitis | 1/28 (3.6%) | 1 |
Infections and infestations | ||
Infections and infestations - Other | 1/28 (3.6%) | 1 |
Lung infection | 1/28 (3.6%) | 1 |
Sepsis | 2/28 (7.1%) | 2 |
Upper respiratory infection | 1/28 (3.6%) | 1 |
Metabolism and nutrition disorders | ||
Dehydration | 1/28 (3.6%) | 1 |
Hyperkalemia | 1/28 (3.6%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Back pain | 1/28 (3.6%) | 1 |
Bone pain | 1/28 (3.6%) | 1 |
Nervous system disorders | ||
Headache | 1/28 (3.6%) | 1 |
Renal and urinary disorders | ||
Acute kidney injury | 1/28 (3.6%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Axitinib | ||
Affected / at Risk (%) | # Events | |
Total | 27/28 (96.4%) | |
Blood and lymphatic system disorders | ||
Anemia | 2/28 (7.1%) | 3 |
Endocrine disorders | ||
Hyperparathyroidism | 1/28 (3.6%) | 1 |
Hypothyroidism | 3/28 (10.7%) | 4 |
Eye disorders | ||
Eye disorders - Other | 2/28 (7.1%) | 2 |
Eye pain | 1/28 (3.6%) | 1 |
Papilledema | 1/28 (3.6%) | 1 |
Gastrointestinal disorders | ||
Abdominal pain | 2/28 (7.1%) | 2 |
Constipation | 5/28 (17.9%) | 5 |
Diarrhea | 8/28 (28.6%) | 10 |
Dry mouth | 2/28 (7.1%) | 3 |
Gastrointestinal disorders - Other | 2/28 (7.1%) | 2 |
Lower gastrointestinal hemorrhage | 1/28 (3.6%) | 2 |
Mucositis oral | 4/28 (14.3%) | 9 |
Nausea | 10/28 (35.7%) | 10 |
Oral dysesthesia | 1/28 (3.6%) | 1 |
Oral pain | 4/28 (14.3%) | 4 |
Rectal perforation | 1/28 (3.6%) | 1 |
Vomiting | 5/28 (17.9%) | 5 |
General disorders | ||
Edema face | 1/28 (3.6%) | 1 |
Fatigue | 21/28 (75%) | 46 |
Neck edema | 1/28 (3.6%) | 1 |
Non-cardiac chest pain | 3/28 (10.7%) | 3 |
Pain | 7/28 (25%) | 7 |
Infections and infestations | ||
Papulopustular rash | 1/28 (3.6%) | 1 |
Upper respiratory infection | 2/28 (7.1%) | 2 |
Urinary tract infection | 2/28 (7.1%) | 2 |
Injury, poisoning and procedural complications | ||
Dermatitis radiation | 3/28 (10.7%) | 3 |
Fall | 2/28 (7.1%) | 3 |
Investigations | ||
Activated partial thromboplastin time prolonged | 1/28 (3.6%) | 1 |
Alanine aminotransferase increased | 2/28 (7.1%) | 2 |
Aspartate aminotransferase increased | 6/28 (21.4%) | 6 |
Blood bilirubin increased | 1/28 (3.6%) | 1 |
Lymphocyte count decreased | 2/28 (7.1%) | 2 |
Platelet count decreased | 1/28 (3.6%) | 1 |
Weight loss | 7/28 (25%) | 9 |
Metabolism and nutrition disorders | ||
Anorexia | 6/28 (21.4%) | 7 |
Dehydration | 3/28 (10.7%) | 3 |
Hypercalcemia | 1/28 (3.6%) | 1 |
Hyperglycemia | 3/28 (10.7%) | 6 |
Hyperkalemia | 3/28 (10.7%) | 3 |
Hypernatremia | 1/28 (3.6%) | 1 |
Hypoglycemia | 2/28 (7.1%) | 2 |
Hypomagnesemia | 1/28 (3.6%) | 1 |
Hyponatremia | 1/28 (3.6%) | 1 |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 1/28 (3.6%) | 1 |
Back pain | 5/28 (17.9%) | 5 |
Musculoskeletal and connective tissue disorder - Other | 1/28 (3.6%) | 1 |
Neck pain | 1/28 (3.6%) | 1 |
Pain in extremity | 2/28 (7.1%) | 2 |
Nervous system disorders | ||
Ataxia | 1/28 (3.6%) | 2 |
Brachial plexopathy | 1/28 (3.6%) | 2 |
Dizziness | 1/28 (3.6%) | 1 |
Dysgeusia | 5/28 (17.9%) | 5 |
Headache | 5/28 (17.9%) | 6 |
Peripheral motor neuropathy | 2/28 (7.1%) | 2 |
Peripheral sensory neuropathy | 1/28 (3.6%) | 1 |
Tremor | 1/28 (3.6%) | 1 |
Psychiatric disorders | ||
Agitation | 1/28 (3.6%) | 1 |
Anxiety | 2/28 (7.1%) | 3 |
Confusion | 1/28 (3.6%) | 1 |
Depression | 3/28 (10.7%) | 3 |
Insomnia | 3/28 (10.7%) | 3 |
Renal and urinary disorders | ||
Acute kidney injury | 1/28 (3.6%) | 1 |
Proteinuria | 2/28 (7.1%) | 5 |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 3/28 (10.7%) | 4 |
Dyspnea | 4/28 (14.3%) | 5 |
Epistaxis | 3/28 (10.7%) | 3 |
Hoarseness | 7/28 (25%) | 9 |
Laryngeal hemorrhage | 1/28 (3.6%) | 1 |
Laryngeal inflammation | 1/28 (3.6%) | 1 |
Nasal congestion | 1/28 (3.6%) | 1 |
Postnasal drip | 1/28 (3.6%) | 1 |
Productive cough | 1/28 (3.6%) | 1 |
Respiratory, thoracic and mediastinal disorders - Other | 1/28 (3.6%) | 1 |
Sinus disorder | 1/28 (3.6%) | 1 |
Sore throat | 4/28 (14.3%) | 6 |
Skin and subcutaneous tissue disorders | ||
Alopecia | 1/28 (3.6%) | 1 |
Hyperhidrosis | 1/28 (3.6%) | 2 |
Palmar-plantar erythrodysesthesia syndrome | 1/28 (3.6%) | 2 |
Rash acneiform | 1/28 (3.6%) | 1 |
Skin and subcutaneous tissue disorders - Other | 2/28 (7.1%) | 3 |
Vascular disorders | ||
Hypertension | 15/28 (53.6%) | 27 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Paul Swiecicki, M.D. |
---|---|
Organization | University of Michigan Rogel Cancer Center |
Phone | 734-647-1017 |
pswiecic@med.umich.edu |
- UMCC 2016.040
- HUM00114022