Axitinib in R/M Salivary Gland Cancers of the Upper Aerodigestive Tract - SGC-AX14
Condition: Salivary Gland Cancers
MeSH terms: Salivary Gland Neoplasms
Study type: Interventional
Phase: Phase 2

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 description: 
      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.
    

Intervention name(s): Axitinib
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Inlyta
Intervention MeSH terms: Axitinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment