Expansion Trial for Axitinib In Head And Neck Cancer

Sponsor
University of Michigan Rogel Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT02762513
Collaborator
National Comprehensive Cancer Network (Other)
29
1
1
43.3
0.7

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

Study Type:
Interventional
Actual Enrollment :
29 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Expansion Trial Evaluating Axitinib in Patients With Unresectable Recurrent, or Metastatic Head and Neck Cancer Utilizing Choi Response Criteria Phase
Actual Study Start Date :
Aug 30, 2016
Actual Primary Completion Date :
Apr 9, 2020
Actual Study Completion Date :
Apr 9, 2020

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

  1. 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

  1. Median Overall Survival Time [Up to approximately 2.5 years]

    median will be calculated by Kaplan-Meier method.

  2. Median Progression Free Survival (PFS) Time [Up to approximately 2.5 years]

    Median will be calculated by Kaplan-Meier method.

  3. 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

  4. 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

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier:
NCT02762513
Other Study ID Numbers:
  • UMCC 2016.040
  • HUM00114022
First Posted:
May 5, 2016
Last Update Posted:
May 5, 2021
Last Verified:
Apr 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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.
3. Secondary Outcome
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.
4. Secondary Outcome
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%
5. Secondary Outcome
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

[Not Specified]

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
Email pswiecic@med.umich.edu
Responsible Party:
University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier:
NCT02762513
Other Study ID Numbers:
  • UMCC 2016.040
  • HUM00114022
First Posted:
May 5, 2016
Last Update Posted:
May 5, 2021
Last Verified:
Apr 1, 2021