Salivary Gland Cancers Clinical Trial
Official title:
Phase II Study on Inlyta® (Axitinib) in Recurrent and/or Metastatic Salivary Gland Cancers (SGCs) of the Upper Aerodigestive Tract
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.
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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01678105 -
A Phase II Study of Dovitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands
|
Phase 2 | |
| Active, not recruiting |
NCT02568267 -
Basket Study of Entrectinib (RXDX-101) for the Treatment of Patients With Solid Tumors Harboring NTRK 1/2/3 (Trk A/B/C), ROS1, or ALK Gene Rearrangements (Fusions)
|
Phase 2 | |
| Recruiting |
NCT05884320 -
Phase II Trial of Sacituzumab Govitecan in Recurrent and/or Metastatic Secretory Gland Cancers
|
Phase 2 |