Temsirolimus and Cetuximab in Patients With Advanced or Metastatic Solid Tumors (TORERO)

Phase I Study of Temsirolimus and Cetuximab in Adults Patients With Advanced or Metastatic Solid Tumors

Cetuximab is an EGFR inhibitor that has shown efficacy alone or in combination in colorectal cancer or head and neck cancer in several phase II/III studies.

Temsirolimus is a new mTOR inhibitor that has shown interesting results in several Phase I/II studies in advance kidney cancer of bad prognosis.

Study hypothesis is that combination of those two compounds and the inhibition of two pathways at the same time will have more efficiency on tumoral growth than the inhibition of those pathways in isolation.

Study Overview

• Status: Unknown
• Conditions: Patients With Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: Cetuximab; Drug: Temsirolimus

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: SORIA Jean Charles, MD, PhD; Phone Number: +33 0142114291; Email: jean-charles.soria@gustaveroussy.fr
• Study Contact Backup: Name: HASSELBERG Rudiger, MD,PhD; Phone Number: +33 0142116250; Email: rudgier.hasselberg@gustaveroussy.fr

Study Locations

• France
  • Val de Marne
    • Villejuif, Val de Marne, France, 94805
      • Recruiting
      • Gustave Roussy
      • Contact: Rudiger HASSELBERG; Phone Number: +33 0142116250; Email: rudiger.hasselberg@gustaveroussy.fr
      • Principal Investigator: Jean Charles SORIA, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with malignant tumor confirmed histologically or cytologically who does not respond to usual therapeutics or for whom there is no curative treatment
• Age >/= 18 years
• ECOG 0 or 1
• Life expectancy >/= 12 weeks
• Grade </=1 for all adverse effects related to previous therapy or surgery (except for alopecia)
• Appropriate organic functions as defined:
• ASAT and ALAT </= 2.5xLSN or ASAT and ALAT </= 5xLSN in case of inappropriate hepatic function due to the underlying disease
• Bilirubin </= 1.5xLSN
• Albumin >/= 3.0 g/dL
• Neutrophil counts (PNN) >/= 1 500/mL
• Platelets >/= 100 000/mL
• Hemoglobin >/= 9.0 g/dL
• Creatinin </= 1.5xLSN
• Cooperative patients able to respect the protocol

Exclusion Criteria:

• Treatment by chemotherapy, radiotherapy, surgery or the two compounds of the study within 4 weeks before the inclusion
• Previous treatment with an association of mTOR inhibitor or EGFR inhibitor
• Diagnosis of a secondary cancer within the last 3 years except for a basal-cell carcinoma, cutaneous spinocellular cancer or in situ carcinoma well treated
• Grade >/= 2 nephropathy according to NCI CTCAE
• Current treatment with curative dose of coumadin or heparin of low molecular weight
• Previous uncontrolled brain metastases, medullar compression or carcinomatosis meningitis or any proof of leptomeningeal pathology or metastasis.
• Presence of one og those pathologies during the last 12 months before the inclusion:
• myocardial infarction
• angina pectoris
• bypass of coronal or peripheral arteries
• heart failure
• stroke
• cerebral bleeding
• pulmonary embolism
• Grade 3 bleeding according to NCI CTCAE criteria less than 3 weeks before treatment start
• Uncontrolled high blood pressure (>150/100mhHg)
• Grade >/=2 heart rate disorder, atrial fibrillation whichever the grade, lengthen of QTC >450 msec for male or >470 msec for female.
• Patients HIV positive
• Pregnant or breastfeeding woman
• Patients with psychiatric disorder
• Active alcoholism
• Previous pulmonary interstitial disease
• Previous hypersensitivity to antihistamine treatment and/or medical contraindication for an antihistamine or corticoid treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cetuximab + Temsirolimus; Cetuximab: 400mg/m² IV for 120 minutes Temsirolimus: 15mg IV for 60 minutes	Drug: Cetuximab; Drug: Temsirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Adverse effects will be assessed using NCI-CTC.AE v.4	Assessed every every week from inclusion during the four first weeks then at week 8 then every 2 months until death or progression whichever comes first up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy	Tumorous response will be assessed using RECIST criteria	Assessed every 2 cycles (44 days) from inclusion up to 24 months

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: August 8, 2014
• First Submitted That Met QC Criteria: August 12, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Estimate): February 10, 2016
• Last Update Submitted That Met QC Criteria: February 9, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus; Cetuximab
• Other Study ID Numbers: 2010-012275-88; 2010/1626 (Other Identifier: CSET number)