KRAS Wild-type Metastatic Colorectal Cancer Trial

NCT00879385 | Completed Phase 1 DMC

• 1 other identifier: HCI31116
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 3.Measure CEA levels at the beginning of each cycle to examine if they correlate with treatment response or disease progression.

Conditions

Colorectal Cancer

Keywords

KRAS wild-type; Colon; Cancer; colorectal; metastatic colorectal; advanced colorectal

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (3)

• 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 years

• 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.

  2 years

• Measure CEA levels at the beginning of each cycle to examine if they correlate with treatment response or disease progression.

  2 years

Study Arms (1)

All patients

EXPERIMENTAL

All participants enrolled.

Drug: Dacogen™ (decitabine); Drug: Vectibix® (panitumumab)

Interventions

Dacogen™ (decitabine) DRUG

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

All patients

Vectibix® (panitumumab) DRUG

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

All patients

Eligibility Criteria

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

You may qualify if:

• At least third line stage IV metastatic colorectal cancer or metastatic colorectal cancer patients intolerant to second line therapy.
• Tumor is KRAS wild-type.
• ECOG performance status of 0-1
• Age (≥)18
• Adequate bone marrow function (ANC \>1500/mm3, hemoglobin \>9 g/dL (which may be obtained by transfusions or growth factor support), platelets \>100,000)
• 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.
• Adequate renal function (Serum creatinine ≤1.5 x ULN or calculated creatinine of \>50 ml/min)
• Timing of the last previous chemotherapy, radiotherapy, immunotherapy, and/or surgery treatment to be greater than 2 weeks before protocol entry
• 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)
• 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.
• Available archived tumor sample or provide consent for re-biopsy of tumor.
• Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
• Patients must have at least one measurable site of disease according to RECIST criteria

You may not qualify if:

• Prior treatment with decitabine.
• Known hypersensitivity to decitabine and panitumumab or their excipients.
• Any of the following within 6 months prior to drug administration: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, or cerebrovascular accident.
• Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2 that are independent of previous treatments.
• Severely impaired lung function by medical history and/or clinical lung exam.
• Any active (acute or chronic) or uncontrolled infection/ disorders.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Hypertension that can not be controlled by medications (\>170/100 mmHg)
• 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)
• Known HIV infection by patient disclosure or on active treatment.
• 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.
• Women of child-bearing age who are pregnant or lactating
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol

Sponsors & Collaborators

• University of Utah: lead
• Amgen: collaborator
• Eisai Inc.: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Garrido-Laguna I, McGregor KA, Wade M, Weis J, Gilcrease W, Burr L, Soldi R, Jakubowski L, Davidson C, Morrell G, Olpin JD, Boucher K, Jones D, Sharma S. A phase I/II study of decitabine in combination with panitumumab in patients with wild-type (wt) KRAS metastatic colorectal cancer. Invest New Drugs. 2013 Oct;31(5):1257-64. doi: 10.1007/s10637-013-9947-6. Epub 2013 Mar 17.

  PMID: 23504398 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasms

Interventions

Decitabine; Panitumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Sunil Sharma, MD

  Huntsman Cancer Institute

  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: April 8, 2009
• First Posted: April 10, 2009
• Study Start: December 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: October 31, 2014

Record last verified: 2014-10

Locations

US (1)