NCT01166035

Lenalidomide and Cetuximab in Patients With Advanced Solid Tumors

Phase 1/2 Study of Lenalidomide and Cetuximab in Patients With Advanced Solid Tumors

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Medical University Innsbruck · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1/2, open-label, monocentric, dose-escalation study of lenalidomide in combination with cetuximab in subjects with solid tumors. The primary objective is to establish the maximum tolerated dose (MTD) of lenalidomide in combination with cetuximab in patients with solid tumors including colorectal cancer (CRC), squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC).

Detailed description

Background: For metastatic cancer such as head and neck, lung and colorectal cancer, standard therapy comprises chemotherapy regimen partially in combination with monoclonal antibodies blocking the vascular endothelial growth factor (VEGF) or the epidermal growth factor receptor (EGFR). When disease progression occurs during or after these treatment options have been applied, no established therapy is available and the clinical development of new strategies is warranted. Lenalidomide (Revlimid®) is a thalidomide derivative and belongs to the so-called ImiDs, a class of immunostimulatory molecules. IMiDs have profound effects on the immune system. Obviously, IMiDs are able to function as co-stimulatory molecule for mature T cells. In addition, IMiDs are able to mitigate the negative effects of CTLA-4 signalling. On the molecular level, IMiDs induce phosphorylation of CD28, underlining the concept that they act as costimulatory signals during T cell activation. Furthermore, the induction of specific CTL responses by dendritic cells (DC) is enhanced and the activity of suppressive regulatory T cells (Treg) inhibited. In addition to their effects on cells of the adaptive immune system, IMiDs also target the innate immune response. Natural killer cells (NK) as well as natural killer T-cells (NKT) are activated by Immunomodulatory Drugs (IMiDs), and the effects of IMiDs on NK and NKT cells might further contribute to the immune-activating properties of ImiDs. Therefore the rationale of the combination of lenalidomide with a therapeutic IgG1 antibody such as cetuximab (Erbitux®) is based on the fact that several reports suggest a role of antibody-dependent cellular cytotoxicity (ADCC) as a mode of action of cetuximab. However, the exact definition of these anti-cancer mechanisms of lenalidomide alone and in combination with cetuximab in vivo require further investigation in early clinical trials. The goal of this phase I/II trial is to define the toxicity of the combination of lenalidomide and cetuximab and to study potential effects on the tumor and the immune system. Subjects meeting all inclusion criteria will be enrolled in cohorts of three patients to receive a single, oral dose of lenalidomide administered on Days 1-28 and intravenous (IV) infusions of cetuximab (400 mg/m2 first infusion only, then 250 mg/m2 subsequently) administered on Days 1, 8, 15, and 22 of each 28-day cycle. Prior to combination therapy, there will be a 21 day lead in treatment period with lenalidomide monotherapy (Days -21 to -1). Combination treatment will start at Day 1. Tumor biopsies will be taken before monotherapy lenalidomide treatment (between d-25 and -22) and between Day -3 and -1 (before starting cetuximab). A third tumor biopsy will be taken between Cycle 1 Day 21 and 28 after starting combination therapy. Cycles will be repeated every 28 days. All subjects will continue on study drug until disease progression, unacceptable toxicity or treatment discontinuation for any other reason. The MTD of lenalidomide will be defined as the highest dose level at which no more than 1 out of 6 subjects experience a dose-limiting toxicity (DLT) during the first cycle of administration in combination with cetuximab. Safety measurements and analysis will be performed at each visit.

Conditions

• Solid Tumors

Interventions

Type	Name	Description
DRUG	Lenalidomide	Lenalidomide will be supplied as 5 mg, 10 mg, 15 mg, 20 mg and 25 mg capsules for oral administration. Prior to Cycle 1, there will be a 21 day lead in treatment period with lenalidomide monotherapy (Days -21 to -1). Combination treatment will start at Day 1. Subjects will be enrolled in cohorts of three to receive a single, oral dose of lenalidomide administered on Days 1-28. For each cohort of subjects, the decision of whether or not to dose-escalate will be made after subjects have received the first treatment cycle of study drug. Treatment will continue until the occurrence of any of the following events. * Disease progression * Adverse event(s) that, in the judgment of the Investigator, may cause severe or permanent harm or which rule out continuation of the treatment regimen. * Major violation of the study protocol. * Withdrawal of consent * Lost to follow up * Death * Suspected pregnancy
DRUG	Cetuximab	Combination treatment will start at Day 1. Subjects meeting will be enrolled in cohorts of three to receive infusions of cetuximab (400 mg/m2 first infusion only, then 250 mg/m2 subsequently) administered on Days 1, 8, 15, and 22 of each 28-day cycle. Cetuximab will be supplied as Erbitux® 22 mg/ml Vial à 50 ml, Erbitux 5 mg/ml Vial à 10 ml and Erbitux 5 mg/ml Vial à 50 ml for intravenous administration. Treatment will continue until the occurrence of any of the following events. * Disease progression * Adverse event(s) that, in the judgment of the Investigator, may cause severe or permanent harm or which rule out continuation of the treatment regimen. * Major violation of the study protocol. * Withdrawal of consent * Lost to follow up * Death * Suspected pregnancy

Timeline

• Start date: 2010-03-01
• Primary completion: 2011-09-01
• Completion: 2011-12-01
• First posted: 2010-07-20
• Last updated: 2010-07-20

Locations

1 site across 1 country: Austria