KRAS Wild-type Metastatic Colorectal Cancer Trial

• Status: Completed
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Utah
• Collaborators: Amgen; Eisai Inc.
• Treatments: Antibodies, Monoclonal; Azacitidine; Decitabine; Panitumumab

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