Trial Outcomes & Findings for Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer (NCT NCT01469546)

Last Updated: 2016-08-29

Results Overview

To determine the 6-months progression-free survival (PFS) rate in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

6 months

Results posted on

2016-08-29

Participant Flow

42 patients were enrolled. 12 patients did not complete the first cycle or undergo repeat tumor imaging (due to adverse event, disease progression, non-compliance or physician discretion). Only 30 patients were analyzed..

Participant milestones

Participant milestones
Measure	Axitinib (AG-013736) 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.
Received 5 mg Dose STARTED	42
Received 5 mg Dose Completed First Cycle	30
Received 5 mg Dose COMPLETED	19
Received 5 mg Dose NOT COMPLETED	23
Dose Escalation to 10 mg STARTED	19
Dose Escalation to 10 mg COMPLETED	19
Dose Escalation to 10 mg NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Axitinib (AG-013736) 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.
Received 5 mg Dose Adverse Event	13
Received 5 mg Dose Death	2
Received 5 mg Dose Protocol Violation	2
Received 5 mg Dose Progressive Disease	3
Received 5 mg Dose Physician Decision	3

Baseline Characteristics

Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axitinib (AG-013736) n=30 Participants 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.
Age, Continuous	62 years n=99 Participants
Sex: Female, Male Female	7 Participants n=99 Participants
Sex: Female, Male Male	23 Participants n=99 Participants

PRIMARY outcome

Timeframe: 6 months

Population: 42 patients were enrolled. 12 patients did not complete the first cycle or undergo repeat tumor imaging (due to adverse event, disease progression, non-compliance or physician discretion). Only 30 patients were analyzed.

To determine the 6-months progression-free survival (PFS) rate in patients with unresectable recurrent and metastatic head and neck cancer treated with Axitinib.

Outcome measures

Outcome measures
Measure	Axitinib (AG-013736) n=30 Participants 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.
Percentage of Patients Alive and Free of Progression at 6 Months	27 percentage of patients

SECONDARY outcome

Timeframe: 2 years

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.

Outcome measures

Outcome measures
Measure	Axitinib (AG-013736) n=30 Participants 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.
Number of Participants Who Achieved Complete Response, Partial Response or Stable Disease	23 participants

SECONDARY outcome

Timeframe: 28 Days Post Treatment

Population: All patients that received at least one dose of treatment were analyzed for toxicity.

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.

Outcome measures

Outcome measures
Measure	Axitinib (AG-013736) n=42 Participants 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.
Number of Patients That Experienced Grade 3 or 4 Toxicities Fatigue	7 patients
Number of Patients That Experienced Grade 3 or 4 Toxicities Rash	5 patients
Number of Patients That Experienced Grade 3 or 4 Toxicities Mucocitis/Stomatitis	3 patients
Number of Patients That Experienced Grade 3 or 4 Toxicities Pain	1 patients
Number of Patients That Experienced Grade 3 or 4 Toxicities Thrombosis	1 patients

SECONDARY outcome

Timeframe: 6 months

To evaluate PFS time in patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN) treated with Axitinib.

Outcome measures

Outcome measures
Measure	Axitinib (AG-013736) n=30 Participants 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.
Median Progression-Free Survival (PFS)Time	3.7 months Interval 3.5 to 5.7

Adverse Events

Axitinib (AG-013736)

Serious events: 22 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Axitinib (AG-013736) n=42 participants at risk 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.
Cardiac disorders Supraventricular and nodal arrhythmia	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Cardiac disorders Sinus tachycardia	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Cardiac disorders Cardiac ischemia/infarction	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Cardiac disorders Pericardial effusion (non-malignant)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Death not associated with CTCAE term	14.3% 6/42 • Number of events 6 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Dehydration	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Obstruction, GI	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Stricture/stenosis (including anastomotic), GI	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Vascular disorders Hemorrhage, GI	7.1% 3/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Vascular disorders Hemorrhage, pulmonary/upper respiratory	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Lung	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Blood	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Skin	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection with unknown ANC, Lung	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Hydrocephalus	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Syncope (fainting)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Pain, Abdomen	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Pain, Chest	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Eye disorders Pain, Eye	2.4% 1/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Pain, Face	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome (ARDS)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Vascular disorders Thrombosis/thrombus/embolism	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.

Other adverse events

Other adverse events
Measure	Axitinib (AG-013736) n=42 participants at risk 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.
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic)	7.1% 3/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Nausea	14.3% 6/42 • Number of events 6 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Vomiting	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Vascular disorders Hemorrhage, GI	4.8% 2/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Vascular disorders Hemorrhage, pulmonary/upper respiratory	2.4% 1/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection - Other	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Bronchus	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Pneumonia	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Immune system disorders Allergic reaction/hypersensitivity	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Blood and lymphatic system disorders Hemoglobin	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Blood and lymphatic system disorders Hemolysis	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Blood and lymphatic system disorders Platelets	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Cardiac disorders Hypertension	16.7% 7/42 • Number of events 10 All 42 patients received treatment and were therefore evaluable for adverse events.
Cardiac disorders Pericardial effusion (non-malignant)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Constitutional Symptoms	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Fatigue (asthenia, lethargy, malaise)	61.9% 26/42 • Number of events 40 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Fever (in the absence of neutropenia)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Weight loss	21.4% 9/42 • Number of events 12 All 42 patients received treatment and were therefore evaluable for adverse events.
Skin and subcutaneous tissue disorders Dry skin	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Skin and subcutaneous tissue disorders Photosensitivity	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Immune system disorders Rash/desquamation	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	9.5% 4/42 • Number of events 12 All 42 patients received treatment and were therefore evaluable for adverse events.
Endocrine disorders Thyroid function, low (hypothyroidism)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Anorexia	19.0% 8/42 • Number of events 10 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Constipation	19.0% 8/42 • Number of events 10 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Dehydration	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Diarrhea	26.2% 11/42 • Number of events 16 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	7.1% 3/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	9.5% 4/42 • Number of events 4 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Fistula, GI	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Flatulence	2.4% 1/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Hemorrhoids	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam)	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Paranasal	4.8% 2/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Upper Airway	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Infections and infestations Infection, Urinary Tract	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Blood and lymphatic system disorders Edema: head and neck	2.4% 1/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Metabolism and nutrition disorders Calcium, serum-high (hypercalcemia)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Metabolism and nutrition disorders Proteinuria	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Musculoskeletal and connective tissue disorders Joint-function	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Musculoskeletal and connective tissue disorders Lumbar spine-range of motion	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Cognitive disturbance	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Confusion	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Dizziness	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Mood alteration	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Neurology	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Neuropathy: sensory	2.4% 1/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Psychosis (hallucinations/delusions)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Eye disorders Ophthalmoplegia/diplopia (double vision)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Eye disorders Watery eye (epiphora, tearing)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Pain, Abdomen	7.1% 3/42 • Number of events 3 All 42 patients received treatment and were therefore evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain, Back	7.1% 3/42 • Number of events 6 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Pain, Chest	7.1% 3/42 • Number of events 4 All 42 patients received treatment and were therefore evaluable for adverse events.
Ear and labyrinth disorders Pain, External Ear	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Nervous system disorders Pain, Head	16.7% 7/42 • Number of events 9 All 42 patients received treatment and were therefore evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain, Muscle	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Musculoskeletal and connective tissue disorders Pain, Neck	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Pain, Oral Cavity	23.8% 10/42 • Number of events 13 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Pain, NOS	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Gastrointestinal disorders Pain, Throat	7.1% 3/42 • Number of events 5 All 42 patients received treatment and were therefore evaluable for adverse events.
General disorders Pain - Other	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 4/42 • Number of events 4 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	9.5% 4/42 • Number of events 5 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	2.4% 1/42 • Number of events 1 All 42 patients received treatment and were therefore evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria	11.9% 5/42 • Number of events 5 All 42 patients received treatment and were therefore evaluable for adverse events.
Renal and urinary disorders Urinary frequency/urgency	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.
Renal and urinary disorders Urinary retention (including neurogenic bladder)	4.8% 2/42 • Number of events 2 All 42 patients received treatment and were therefore evaluable for adverse events.

Additional Information

Dr. Francis Worden, M.D.

University of Michigan Comprehensive Cancer Center

Phone: 734-936-0453

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place