KRAS Wild-type Metastatic Colorectal Cancer Trial

This study has been completed.
Sponsor:
Collaborators:
Amgen
Eisai Inc.
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00879385
First received: April 8, 2009
Last updated: April 10, 2013
Last verified: April 2013
  Purpose

OBJECTIVES:

Primary Objectives

1.To evaluate the safety and feasibility of the sequential use of a DNA methyltransferase (DNMT) inhibitor (decitabine) with a targeted biological agent against EGFR (panitumumab) for KRAS wild type tumors in the second or third line treatment of advanced metastatic colorectal cancer.

Secondary Objectives

  1. To examine re-expression or a reduction in promoter methylation in genes involved in tumor suppressor pathways known to be important in colorectal cancer (CRC) or involved in EGFR signaling pathway.
  2. Evaluate overall response (OR = CR +PR) according to RECIST criteria at 2, 4, and 6 cycles. Progression free survival, measured as the first evidence of tumor growth from the start of treatment will also be assessed.
  3. Measure CEA levels at the beginning of each cycle to examine if they correlate with treatment response or disease progression.

Condition Intervention Phase
Colorectal Cancer
Drug: Dacogen™ (decitabine)
Drug: Vectibix® (panitumumab)
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Targeted Demethylation to Enhance Response or Overcome Resistance to EGFR Blocking Agents in KRAS Wild-type Metastatic Colorectal Cancer Patients Using Sequential Decitabine and Panitumumab

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Evaluate safety & feasibility of sequential use of a DNA methyltransferase (DNMT) inhibitor (decitabine) with targeted biological agent against EGFR (panitumumab) for KRAS wild type tumors in second or third line treatment of colorectal cancer. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To examine re-expression or a reduction in promoter methylation in genes involved in tumor suppressor pathways known to be important in colorectal cancer (CRC) or involved in EGFR signaling pathway. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate overall response (OR = CR +PR) according to RECIST criteria at 2, 4, and 6 cycles. Progression free survival, measured as the first evidence of tumor growth from the start of treatment will also be assessed. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Measure CEA levels at the beginning of each cycle to examine if they correlate with treatment response or disease progression. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: December 2009
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
All participants enrolled.
Drug: Dacogen™ (decitabine)

Dacogen™ (decitabine) is a FDA approved drug (NDA - 021790) for the treatment of myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia).

Decitabine will be given on this study at 45 mg/m2 IV over 2 hrs

Other Name: Dacogen™ (decitabine)
Drug: Vectibix® (panitumumab)

Vectibix® (panitumumab) is a FDA approved drug (BLA-125147) indicated as a single agent for the treatment of EGFR-expressing metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan chemotherapy regimens. Approval is based on progression-free survival; no data demonstrate an improvement in disease-related symptoms or increased survival.

DRUG DESCRIPTION Vectibix® (panitumumab) is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). Panitumumab has an approximate molecular weight of 147 kDa. Panitumumab is produced in genetically engineered mammalian (Chinese Hamster Ovary) cells.

Panitumumab will be given on this study at 6 mg/kg, IV over 1 hr

Other Name: Vectibix® (panitumumab)

  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. At least third line stage IV metastatic colorectal cancer or metastatic colorectal cancer patients intolerant to second line therapy.
  2. Tumor is KRAS wild-type.
  3. ECOG performance status of 0-1
  4. Age (≥)18
  5. Adequate bone marrow function (ANC >1500/mm3, hemoglobin >9 g/dL (which may be obtained by transfusions or growth factor support), platelets >100,000)
  6. Adequate hepatic function (AST and ALT <2.5x upper limit of normal (ULN), unless there are liver metastasis in which case AST and ALT <5.0 x ULN.
  7. Adequate renal function (Serum creatinine ≤1.5 x ULN or calculated creatinine of >50 ml/min)
  8. Timing of the last previous chemotherapy, radiotherapy, immunotherapy, and/or surgery treatment to be greater than 2 weeks before protocol entry
  9. Patients are required to have recovered from side effects of prior treatment with the exception of neuropathy (to be determined by treating physician and NCI CTCAE grade <1)
  10. Women of child-bearing age must be willing to use adequate contraception and have negative serum or urine pregnancy test within 3 days prior to registration.
  11. Available archived tumor sample or provide consent for re-biopsy of tumor.
  12. Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
  13. Patients must have at least one measurable site of disease according to RECIST criteria

Exclusion Criteria:

  1. Prior treatment with decitabine.
  2. Known hypersensitivity to decitabine and panitumumab or their excipients.
  3. Any of the following within 6 months prior to drug administration: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, or cerebrovascular accident.
  4. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2 that are independent of previous treatments.
  5. Severely impaired lung function by medical history and/or clinical lung exam.
  6. Any active (acute or chronic) or uncontrolled infection/ disorders.
  7. Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
  8. Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  9. Hypertension that can not be controlled by medications (>170/100 mmHg)
  10. Diagnosis of any secondary malignancy within the last 3 years (except basal cell carcinoma, squamous cell skin cancer, or stage I or less carcinoma fully treated)
  11. Known HIV infection by patient disclosure or on active treatment.
  12. Other severe acute or chronic medical or psychiatric condition or lab abnormality that would place the participant at excess risk by participating as judged by the study investigator.
  13. Women of child-bearing age who are pregnant or lactating
  14. History of noncompliance to medical regimens
  15. Patients unwilling to or unable to comply with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879385

Locations
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Amgen
Eisai Inc.
Investigators
Principal Investigator: Sunil Sharma, MD Huntsman Cancer Institute
  More Information

No publications provided by University of Utah

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00879385     History of Changes
Other Study ID Numbers: HCI31116
Study First Received: April 8, 2009
Last Updated: April 10, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Utah:
KRAS wild-type
Colon
Cancer
colorectal
metastatic colorectal
advanced colorectal

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Decitabine
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014