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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01432119
First received: September 8, 2011
Last updated: April 8, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Advanced Cancers
Device: SIR-Spheres
Drug: Cetuximab
Drug: Erlotinib
Procedure: Break-Through Scan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Cetuximab and Erlotinib (EGFR Inhibitors) and SIR-Spheres (Yttrium Microspheres) in Patients With Advanced Malignancies and Liver Metastases

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 0
Study Start Date: December 2012
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 SIR-Spheres + Cetuximab
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
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.
Drug: Cetuximab
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.
Other Names:
  • C225
  • Erbitux
Procedure: Break-Through Scan
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.
Other Name: x-ray
Experimental: Arm 2 SIR-Spheres + Cetuximab + Erlotinib.
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
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.
Drug: Cetuximab
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.
Other Names:
  • C225
  • Erbitux
Drug: Erlotinib
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.
Other Names:
  • Erlotinib Hydrochloride
  • OSI-774
  • Tarceva
Procedure: Break-Through Scan
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.
Other Name: x-ray

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 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
  3. ECOG performance status </= 3.
  4. 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
  5. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence).
  6. Patients must be able to understand and be willing to sign a written informed consent document.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Patients who have had hepatic external beam radiotherapy.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres, cetuximab, or erlotinib.
  4. Patients with colorectal cancer with known kRAS mutation
  5. Hepatic arterial anatomy that would prevent catheterization and the administration of SIR-Spheres into the liver.
  6. 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
  7. 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.
  8. 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.
  9. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01432119

Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Aung Naing, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01432119     History of Changes
Other Study ID Numbers: 2011-0552
Study First Received: September 8, 2011
Last Updated: April 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancies
Liver Metastases
SIR-Spheres
Selective internal radiation
Yttrium-90
Cetuximab
C225
Erbitux
Erlotinib
Erlotinib Hydrochloride
Tarceva
OSI-774

Additional relevant MeSH terms:
Neoplasms
Cetuximab
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014