Axitinib in R/M Salivary Gland Cancers of the Upper Aerodigestive Tract - SGC-AX14

NCT02857712 | Completed Phase 2

• 1 other identifier: INT 135/14
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

SGCs are rare (less than 1% of head and neck cancers) and include many malignant histotypes. SGCs are treated mainly with surgery, followed by radiotherapy in selected cases. Chemotherapy is reserved for palliative treatment of metastases or local recurrence but results in term of response rate are very low. Adenoid cystic cancer (ACC) is the most common SGC histotype observed in metastatic subjects while the other histotypes (non-ACC) such as mucoepidermoid cancer (MEC), salivary duct gland cancer, adenocarcinoma, myoepithelial carcinoma are more uncommon. A phase II trial with sorafenib carried out in 37 subjects (19 ACC and 18 non-ACC) with recurrent and/or metastatic SGCs showed a response rate of 16% (11% in ACC and 22% in non-ACC). In preclinical models, VEGF seems to contribute to tumor aggressiveness and to distant metastatization of SGCs, in particular in ACC and MEC. Remarkably three confirmed partial responses, one ACC, one renal cancer and one lung cancer, on 36 patients were observed in a phase I study with Inlyta, a potent VEGFR specific-inhibitor approved by FDA as second line treatment for renal cancer. Based on these data, we want to test Inlyta in patients with relapsed and/or metastatic SGC.

Conditions

Salivary Gland Cancers

Outcome Measures

Primary Outcomes (1)

• Objective response rate (CR+PR)

  Objective response rate (CR+PR) will be evaluated according to RECIST response evaluation criteria 1.1 at any subsequent re-evaluation

  2 years and 7 months

Secondary Outcomes (4)

• Progression free survival

  2 years and 7 months

• Overall survival

  2 years and 7 months

• Evaluation acute toxicity (according to CTCAE v4.0)

  2 years and 7 months

• Duration of response

  2 years and 7 months

Study Arms (1)

Axitinib

EXPERIMENTAL

Axitinib will be administered at 5 mg BID (starting dose); in case of no adverse events above CTCAE version 4.0 Grade 2 for a consecutive 2-week periods, the dose may be increased to 7 mg BID and further to 10 mg BID using the same criteria until tumor progression, unacceptable toxicity or other criteria for discontinuation is met.

Drug: Axitinib

Interventions

Axitinib DRUG

Axitinib will be self orally administered at 5 mg twice daily approximately every 12 hours, on a continuous basis (each morning and evening), in 4 week cycles until tumour progression, unacceptable toxicity or other criteria for discontinuation is met. Patients who tolerate axitinib with no adverse events axitinib-related should have a dose increased until to 10 mg twice.

Also known as: Inlyta

Axitinib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven relapsed and/or metastatic salivary gland cancer for which potentially curative options such as surgery or radiotherapy are not indicated.
• Archival tissue samples or unstained 20 slides from primary tumor or metastasis for translational biological research.
• Subjects with at least one uni-dimensional measurable lesion by CT-scan or MRI according to RECIST criteria 1.1 (target lesion). A previously treated lesion by radiotherapy can be chosen as target lesion only if progression in the respective lesion has been demonstrated during or following radiotherapy.
• Clinical or radiological progression of disease within 6 months at study entry. Progression of disease by RECIST is not required.
• Age ≥18 years
• ECOG Performance Status \< 2
• Life expectancy of \> 3 months
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
• Hemoglobin \>9.0 g/dl
• Neutrophil count (ANC) \>1,000/mm3
• Platelet count ≥ 75,000/µl
• Total bilirubin \< 1.5 times the upper limit of normal
• ALT and AST \< 2.5 x upper limit of normal (\<5 x upper limit of normal for patients with liver metastases)
• Serum creatinine \<1.5 x upper limit of normal
• Urinary protein \< 2+ by urine dipstick

You may not qualify if:

• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry
• Previous systemic therapy for metastatic disease is not allowed (chemotherapy or TKI)
• History of cardiac disease: congestive heart failure \>NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
• Known allergic reaction to any of the components of the treatment
• Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
• Legal incapacity or limited legal capacity
• Active clinically serious infections (\> grade 2 NCI-CTC version 4.0)
• Medical or psychological condition which, in the opinion of the investigator, would not enable the patient to complete the study or knowingly sign the Informed Consent
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial
• Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis and T1\] or any cancer curatively treated \> 3 years prior to study entry.
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft.
• Patients with evidence or history of bleeding diathesis
• Gastrointestinal abnormalities (i.e. inability to take oral medication; malabsorption syndrome)
• Requirement for anticoagulant therapy with oral vitamin K antagonists

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

MeSH Terms

Conditions

Salivary Gland Neoplasms

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Lisa Licitra

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: August 5, 2016
• Study Start: December 1, 2014
• Primary Completion: October 1, 2018
• Study Completion: January 1, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)