Pazopanib in Patients With Progressive Recurrent and/or Metastatic Salivary Gland Carcinoma

In the non-ACC SGCHN population, assessment of the activity of pazopanib is exploratory without a predetermined study design, with up to 20 patients. A planned interim analysis of acute toxicities was conducted 3 months after the 14th non-ACC inclusion.

ACC As the endpoint will be evaluated at 6 months after treatment start, a one-stage phase II study design was chosen. The unacceptable 6-month rate of progression free survival is 20% and the promising 6-month rate of progression free survival is 40%.

43 patients are to be treated. If ≤12 patients alive without progression at 6 months will be observed, the drug will be declared ineffective.

If ≥13 patients alive without progression at 6 months will be observed, the drug will be declared promising.

The α error rate (accepting a poor treatment) is 0.07 and the β error rate (rejecting a promising treatment) is 0.07.

Analysis of results will be separated between non ACC and ACC.

Inclusion criteria

• Histologically confirmed diagnosis of recurrent and/or metastatic salivary glands (including ACC and non ACC).
• Progressive disease within 6 months before inclusion as assessed by CT and/or MRI using at least two measurements (RECIST v1.0) with at least one measurable target lesion >10 mm.
• Recurrent and/or metastatic salivary glands carcinoma failing locoregional therapy, without possibility of curative treatment.
• Patients may have had unlimited prior therapy but must have had at least 4 weeks between any chemotherapy, radiotherapy, surgery and study enrollment.
• Tumoral tissue must be provided for subsequent histological review and biomarker analysis.
• Euthyroid patient.
• Hepatic, renal, cardiac and hematology normal functions.
• Ability to take oral medication.

Exclusion criteria

• Non salivary gland carcinoma (lachrymal gland tumor is excluded).
• Known or symptomatic cerebral metastasis.
• Patients treated with strong inhibitor or inductor of CYP3A4 within 14 days before inclusion.
• Presence of uncontrolled infection.
• Diagnosis of any previous malignancy within the last 5 years, except for completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma.
• Stable disease.
• Corrected QT interval (QTc) >480 msecs using Bazett's formula.