Efficacy Study of Temsirolimus to Treat Head and Neck Cancer

A Single Arm, Open-label Multicenter Phase II Trial of Temsirolimus in Patients With Relapsed/Recurrent Squamous Cell Cancer of the Head and Neck (HNSCC)

The purpose of this study is to determine whether temsirolimus is effective in the treatment of relapsed/recurrent squamous cell cancer of the head and neck (HNSCC)

Temsirolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a crucial regulator of cell cycle progression. It was approved in the treatment of advanced renal cell carcinoma. Temsirolimus demonstrated also antitumor activity in a variety of other human cancer models, such as gliomas, rhabdomyosarcomas, neuroblastomas, prostata and breast cancer through induction of apoptosis or inhibition of proliferation. A similar effect was noted in HNSCC cell lines.

This is the first study evaluating the efficacy and safety of temsirolimus in platinum/cetuximab-refractory HNSCC.

Inclusion Criteria:

• Signed written informed consent must be given prior to study inclusion
• Histological or cytological confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC)
• Measurable progressive disease after platinum-based radiochemotherapy or recurrence or metastatic progressive disease after 1st line platinum-based chemotherapy
• Patients with loco-regional recurrence need to be progression free for at least 6 months after platinum-based radiochemotherapy, if locoregional recurrence is the only lesion
• Cetuximab must have been included in at least one prior line of therapy
• Disease is not amenable to surgery, radiotherapy or platinum-based chemotherapy
• At least one measurable lesion according to RECIST (Version 1.0) criteria
• Age > 18 years
• ECOG performance status 0-2
• Brain metastases require completion of local therapy with discontinuation of steroids prior to start of treatment
• If of childbearing potential, willingness to use effective contraceptive method (double barrier method) for the study duration and 2 months after last dose
• Willingness and ability to comply with the protocol
• Adequate bone marrow function, liver and renal function

Exclusion Criteria:

• Live expectancy less than 3 months
• Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
• Participation in a clinical trial within the last 30 days prior to study treatment
• Serious illness or medical condition other than the disease under study
• Other malignancies within 3 years, with exception of HNSCC, history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
• Inability to potentially complete follow up and treatment per protocol for psychological, familial, sociological or geographical reasons
• Pregnancy or breast feeding
• Known allergic/hypersensitivity reaction to any component of the treatment
• Concurrent treatment with oral anticoagulants
• Uncontrolled diabetes: fasting serum glucose > 2.0 ULN
• Active or uncontrolled infection