Sirolimus and Cetuximab in Advanced Malignancies

NCT00940381 | Completed Phase 1

• 2 other identifiers: 2009-0226NCI-2012-01271
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of the combination of sirolimus and cetuximab that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.

Conditions

Advanced Cancer

Keywords

Advanced Malignancies; Sirolimus; Rapamune; Cetuximab; C225; Erbitux; IMC-225

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab

  MTD defined by DLTs that occur in the first cycle (4 weeks). DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, expected and believed to be related to the study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI-CTC v3.0) or associated with bleeding and/or sepsis; any grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 that is attributable to therapy.

  4 weeks

Study Arms (1)

Sirolimus + Cetuximab

EXPERIMENTAL

Sirolimus beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. Cetuximab Beginning dose 100 mg/m\^2 by vein over two hours on Day 1, and 65 mg/m\^2 on Days 8, 15 and 22 for a 28 day cycle.

Drug: Sirolimus; Drug: Cetuximab

Interventions

Sirolimus DRUG

Beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle.

Also known as: Rapamune

Sirolimus + Cetuximab

Cetuximab DRUG

Beginning dose 100 mg/m\^2 by vein over two hours on Day 1, and 65 mg/m\^2 on Days 8, 15 and 22 for a 28 day cycle.

Also known as: C225, Erbitux, IMC-225

Sirolimus + Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
• Patients must be \>/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be \>/= 5 half-lives or \>/= 3 weeks form the last dose (whichever comes first).
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 3.
• Patients must have normal organ and marrow function defined as: absolute neutrophil count \>/= 1,000/mL; platelets \>/=50,000/mL; creatinine \</= 3 X upper limit of normal (ULN); total bilirubin \</= 2.0; ALT(SGPT) \</= 5 X ULN; Exception for patients with liver metastasis: total bilirubin \</= 3 x ULN; ALT(SGPT) \</= 8 X ULN; cholesterol \</= 350 mg/dL; triglycerides \</= 400 mg/dL.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
• Patients with colorectal cancer with Kirsten rat sarcoma (kRAS) mutations (mutational status must be available prior to entering the study)
• Patients must be able to understand and be willing to sign a written informed consent document.

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
• Pregnant or lactating women.
• History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
• History of hypersensitivity to sirolimus.
• History of hypersensitivity to any component of the formulation.
• Patients with colorectal cancer with kRAS mutations. (mutational status must be available prior to entering the study)
• Patients unwilling or unable to sign informed consent document.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Interventions

Sirolimus; Cetuximab

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Filip Janku, MD,PHD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: July 16, 2009
• Study Start: July 1, 2009
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 18, 2015

Record last verified: 2014-05

Locations

US (1)