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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study on Inlyta® (Axitinib) in Recurrent and/or Metastatic Salivary Gland Cancers (SGCs) of the Upper Aerodigestive Tract

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.

Detailed Summary:

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
Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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)
  • Quality of life [ Time Frame: 2 years and 7 months ]
    To assess the quality of life will be administered the questionnaires EORTC QLQ-C30, EORTC QLQ H&N35


Original Secondary Outcome: Same as current

Information By: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Dates:
Date Received: May 6, 2016
Date Started: December 2014
Date Completion: January 2018
Last Updated: August 2, 2016
Last Verified: May 2016