Phase 1 Trial With SIR-Spheres and Cetuximab +/- Erlotinib

NCT01432119 | Withdrawn Phase 1

• 1 other identifier: 2011-0552
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to find the highest tolerable dose of the combination of selective internal radiation (SIR)-Spheres with yttrium-90 attached and cetuximab. Some participants will also take erlotinib with this combination. Yttrium-90 microspheres are designed to treat cancer that has spread to the liver. SIR-Spheres are designed to deliver the radiation directly to the liver. This radiation may cause the tumor cells to die. Cetuximab and erlotinib are drugs that are designed to block the epidermal growth factor receptor (EGFR). EGFR is a protein that helps cancer cells grow. Blocking the EGFR may stop tumors from growing.

Conditions

Advanced Cancers

Keywords

Advanced Cancers; Advanced Malignancies; Liver Metastases; SIR-Spheres; Selective internal radiation; Yttrium-90; Cetuximab; C225; Erbitux; Erlotinib; Erlotinib Hydrochloride; Tarceva; OSI-774

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Maximum tolerated dose (MTD) is defined as the highest dose studied in which the incidence of dose limiting toxicities (DLT) was less than 33% of treated population.

  8 weeks

Study Arms (2)

Arm 1 SIR-Spheres + Cetuximab

EXPERIMENTAL

Arm 1: SIR-Spheres with yttrium-90 attached and cetuximab. SIR-Spheres Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.

Device: SIR-Spheres; Drug: Cetuximab; Procedure: Break-Through Scan

Arm 2 SIR-Spheres + Cetuximab + Erlotinib.

EXPERIMENTAL

Arm 2: SIR-Spheres with yttrium-90 attached, cetuximab, and erlotinib. Physicians will assign patients to Arm 1 or Arm 2 based on their discretion. SIR-Spheres on Day 1 of Cycle 1; Cetuximab start 200 mg/m2 by vein (IV) Weeks 2-4 of Cycle 1, then weekly Cycles 2+. 28-day Cycles. Erlotinib start 100 mg by mouth daily starting with Cycle 2. 28-day Cycles. Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.

Device: SIR-Spheres; Drug: Cetuximab; Drug: Erlotinib; Procedure: Break-Through Scan

Interventions

SIR-Spheres DEVICE

100% full dose SIR-Spheres on Day 1 of Cycle 1. SIR-Spheres with yttrium-90 microspheres will be given through a catheter in a vein in the groin.

Arm 1 SIR-Spheres + Cetuximab; Arm 2 SIR-Spheres + Cetuximab + Erlotinib.

Cetuximab DRUG

Starting Dose: 200 mg/m2 by vein weekly. During Cycle 1, patients will receive cetuximab during Weeks 2-4. In Cycles 2 and beyond, patients will receive cetuximab weekly.

Also known as: C225, Erbitux

Arm 1 SIR-Spheres + Cetuximab; Arm 2 SIR-Spheres + Cetuximab + Erlotinib.

Erlotinib DRUG

Starting dose: 100 mg by mouth daily. Erlotinib will be given starting with Cycle 2 at 100 mg by mouth daily. If tolerated, the dose will be increased to 150 mg by mouth daily in Cycle 3.

Also known as: Erlotinib Hydrochloride, OSI-774, Tarceva

Arm 2 SIR-Spheres + Cetuximab + Erlotinib.

Break-Through Scan PROCEDURE

Nuclear medicine "break-through" scan performed within 29 days before receiving SIR-Spheres. The results of this test will be used to determine if a full or partial dose of SIR-Spheres with yttrium-90 microspheres will be delivered.

Also known as: x-ray

Arm 1 SIR-Spheres + Cetuximab; Arm 2 SIR-Spheres + Cetuximab + Erlotinib.

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 in the liver, with measureable or evaluable disease, 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
• ECOG performance status \</= 3.
• Patients must have organ and marrow function defined as: • Absolute neutrophil count \>/= 500/mL; • Platelets \>/=50,000/mL; creatinine \</= 2 X ULN; • Total bilirubin \</= 2.0; ALT(SGPT) \</= 5 X ULN
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence).
• Patients must be able to understand and be willing to sign a written informed consent document.

You may not qualify if:

• Pregnant or lactating women.
• Patients who have had hepatic external beam radiotherapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres, cetuximab, or erlotinib.
• Patients with colorectal cancer with known kRAS mutation
• Hepatic arterial anatomy that would prevent catheterization and the administration of SIR-Spheres into the liver.
• Greater than 20% arterio-venous shunting of SIR-Spheres to the lungs estimated from a Technetium-99m-macro-aggregated albumin (99mTc-MAA) nuclear medicine break-through scan
• Contraindication to angiography and selective visceral catheterization: History of severe allergy or intolerance to any contract media, or atropine. Bleeding diathesis, not correctable by usual forms of therapy that would include medical coagulopathy but not limited to the administration of blood products.
• Utilization of capecitabine for the 6 weeks preceding SIR-Spheres therapy and indefinitely following SIR-Spheres therapy as per manufacturer's recommendations due to the increased risk of radiation hepatitis.
• Evidence of ascites, biopsy proven cirrhosis, or portal hypertension suggested by the presence of characteristic imaging features on cross-sectional imaging or esophageal varicosities, demonstrated on endoscopy or barium swallow. A diagnostic study to rule out the presence of portal hypertension will not be required unless the findings on cross sectional imaging are suggestive, but not confirmatory.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• UT MD Anderson Website

MeSH Terms

Interventions

Cetuximab; Erlotinib Hydrochloride; X-Rays

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Aung Naing, MD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2011
• First Posted: September 12, 2011
• Study Start: December 1, 2012
• Primary Completion: December 1, 2019
• Last Updated: April 9, 2013

Record last verified: 2013-04