Axitinib in R/M Salivary Gland Cancers of the Upper Aerodigestive Tract - SGC-AX14 (SGC-AX14)
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|ClinicalTrials.gov Identifier: NCT02857712|
Recruitment Status : Completed
First Posted : August 5, 2016
Last Update Posted : August 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Salivary Gland Cancers||Drug: Axitinib||Phase 2|
Carcinomas of the salivary glands (SGCs) are rare, (less than 1% of all cancers of the head and neck and include more than 20 malignant histotypes). They can occur both in major and minor salivary glands, are locally aggressive, demonstrating invasiveness that leads to involvement of the facial nerve, skin, bone and surrounding soft tissue. The standard treatment is surgical excision, followed by radiotherapy in selected cases such as high-grade histotypes, advanced disease and neck nodes diffusion. Loco-regional recurrence occurs in 16% to 85%, it can be managed in very selected cases with further surgery and/or radiotherapy, although the prognosis of these patients remains poor. Adenoid cystic cancer (ACC) is the most common SGC histotype observed in metastatic subjects (60%), while the other histotypes (non-ACC) such as mucoepidermoid cancer (MEC), salivary duct gland cancer, adenocarcinoma, myoepithelial carcinoma are more uncommon. Distant metastases are the principal cause of failure, being diagnosed in 25-55% of the patients. Only 20% of the patients with distant metastases is alive at 5 years. First-line treatment is palliative chemotherapy that is typically not associated with solid data showing any benefit neither in response rate nor in outcome. Very recently a phase II trial with sorafenib has been carried out in 37 subjects (19 ACC and 18 non-ACC) with recurrent and/or metastatic SGCs. Interestingly, a response rate of 16% (95% CI 6,2-32,0) was observed, 11% in ACC and 22% in non-ACC cases with two outstanding responses in patients with an high-grade MEC. In one case the metastatic lesion evolved in a cavitation as observed with antiangiogenic agents. In preclinical models, VEGF seems to contribute to tumor aggressiveness as well as 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®. These results prompted a phase II study to test the activity of axitinib in relapsed and/or metastatic and progressive ACC patients. Results were 9% of partial responses and 75% of stable disease as best overall response. Inlyta®, a potent VEGFR specific-inhibitor, has been approved by FDA as second line treatment for renal cancer. Based on preclinical and clinical data, we believe that targeting VEGFR might represent a rational basis to further test Inlyta® in patients with relapsed and/or metastatic ACC but also in subjects with recurrent/metastatic non-ACC .
Open-label, monocentric, single arm phase II study evaluating the activity and safety of axitinib in recurrent and/or metastatic tumors of salivary gland. 26 patients with histologically proven relapsed or metastatic SGC, progressed within 6 months at study entry will be enrolled over two years. A 2-stage Simon design will be applied: 15 patients enrolled into step one and if a least 1/15 response is observed, 11 additional patients will be enrolled into second step. Axitinib will be administered orally at 5 mg twice daily to patients for the first two weeks. Patients who tolerate axitinib with no adverse events axitinib-related should have a dose increased until to 10 mg twice. The drug will be taken until progression of disease or intolerable toxicity. Tissue paraffin block from primary lesion or metastasis will be collected for CRTC1-MAML2 translocation analysis in MEC; MYB-NFIB translocation analysis in ACC; androgen receptor and HER2 analysis in SDC and adenocarcinoma NOS.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study on Inlyta® (Axitinib) in Recurrent and/or Metastatic Salivary Gland Cancers (SGCs) of the Upper Aerodigestive Tract|
|Study Start Date :||December 2014|
|Actual Primary Completion Date :||October 2018|
|Actual Study Completion Date :||January 2019|
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.
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.
Other Name: Inlyta
- Objective response rate (CR+PR) [ Time Frame: 2 years and 7 months ]Objective response rate (CR+PR) will be evaluated according to RECIST response evaluation criteria 1.1 at any subsequent re-evaluation
- Progression free survival [ Time Frame: 2 years and 7 months ]PFS according to RECIST criteria 1.1
- Overall survival [ Time Frame: 2 years and 7 months ]After study drug treatment ends, patients will be contacted each 6 months to determine survival status.
- Evaluation acute toxicity (according to CTCAE v4.0) [ Time Frame: 2 years and 7 months ]Acute toxicity according to CTCAE v4.0
- Duration of response [ Time Frame: 2 years and 7 months ]The duration of response will be evaluated to assess the duration of activity of axitinib (CR+PR+SD)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02857712
|Fondazione IRCCS Istituto Nazionale dei Tumori|
|Milan, Italy, 20133|
|Principal Investigator:||Lisa Licitra||Fondazione IRCCS Istituto Nazionale dei Tumori, Milano|