New Individualized Therapy Trial for Metastatic Colorectal Cancer

NCT00867334 | Completed Phase 1 Results

• 1 other identifier: CSTI571BUS278T
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of imatinib mesylate in combination with panitumumab for the treatment of stage IV colorectal cancer that has spread to the liver. It will also assess the whether imatinib mesylate, either alone or in combination with panitumumab, is effective in treating this type of cancer. In addition, the study will evaluate the feasibility of a predefined lab score and whether it can predict which patients will respond to treatment with imatinib mesylate.

Conditions

Colorectal Neoplasm; Colorectal Cancer

Keywords

colorectal neoplasm; colorectal cancer; imatinib mesylate; Gleevec; Physiological Effects of Drugs; panitumumab; Vectibix; c-kit receptor; Receptor; Platelet-Derived Growth Factor alpha

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Adverse Events

  Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, will be collected and recorded.

  From consent up until 4 weeks after patient has stopped study participation

Secondary Outcomes (1)

• Number of Participants With Stabilization or Reduction in Tumor Size

  8 weeks after baseline

Study Arms (2)

Imatinib mesylate and panitumumab

EXPERIMENTAL

Subjects whose initial liver biopsy samples meet certain lab values will be placed in Arm 1. Each participant assigned to Arm 1 will receive imatinib mesylate for 28 days, followed by a combination of imatinib mesylate and panitumumab.

Drug: Imatinib mesylate and panitumumab

Panitumumab (standard-of-care)

ACTIVE COMPARATOR

Subjects whose initial liver biopsy samples meet certain lab values will be placed in Arm 2. Participants in Arm 2 will receive standard-of-care treatment with panitumumab.

Drug: Standard-of-care treatment with panitumumab

Interventions

Imatinib mesylate and panitumumab DRUG

Patients will be entered into sequential cohorts with escalating doses of imatinib mesylate. After approximately 28 days of monotherapy treatment with imatinib mesylate, patients will be asked to have a liver biopsy performed (this biopsy is voluntary and is not required for continued participation in the study). All patients in this group will then receive imatinib mesylate in combination with standard-of-care doses of panitumumab. After approximately 1-2 months of combination treatment, patients will asked to have an additional liver biopsy performed (this biopsy is voluntary and is not required for continued participation in the study). Combination treatment will continue for the remainder of the subject's time in the trial.

Also known as: Gleevec, ST1571

Imatinib mesylate and panitumumab

Standard-of-care treatment with panitumumab DRUG

Panitumumab as standard of care. After approximately 2-3 months of standard of care treatment, patients will asked to have a liver biopsy performed (this biopsy is voluntary and is not required for continued participation in the study).

Also known as: Vectibix, ABX-EGF monoclonal antibody

Panitumumab (standard-of-care)

Eligibility Criteria

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

You may qualify if:

• Patients ≥ 18 years of age.
• Histologically documented diagnosis of Stage IV Metastatic Colorectal Cancer with Liver Metastases, refractory or progressive after at least one (1) prior line of therapy that must include a fluoropyrimidine (5-fluorouracil or capecitabine) AND (oxaliplatin OR irinotecan), i.e. FOLFOX, FOLFIRI, XELOX, or XELIRI.
• Documentation of wild type k-Ras expression in the liver lesion.
• At least one measurable site of disease (as defined by Response Evaluation Criteria in Solid Tumors, see Appendix 3), or other response assessment criteria, as appropriate.
• Must have ≥ 1 measurable liver lesion that can be accessed by CT guided biopsy.
• Performance status 0,1, or 2 (ECOG).
• Adequate end organ function, defined as the following: total bilirubin \< 1.5 x ULN, SGOT and SGPT \< 2.5 x UNL, creatinine \< 1.5 x ULN, ANC \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L.
• Life expectancy of at least 3 months.
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 7 days following discontinuation of study drug.
• Written, voluntary informed consent.

You may not qualify if:

• Patient has received any other investigational agents within 28 days of first day of study drug dosing, unless the disease is rapidly progressing.
• Patient is \< 5 years free of another primary malignancy except: if the other primary malignancy is neither currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
• Female patients who are pregnant or breast-feeding.
• Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
• Patient has a known brain metastasis not treated with definitive therapy with stable disease ≥ 4 weeks.
• Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
• Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
• Patient received chemotherapy within 2 weeks (6 weeks for nitrosourea or mitomycin-C)prior to study entry, unless the disease is rapidly progressing.
• Patient previously received radiotherapy to ≥ 25% of the bone marrow
• Patient had a major surgery within 2 weeks prior to study entry.
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• Patients intolerant to imatinib mesylate.

Sponsors & Collaborators

• Inova Health Care Services: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Inova Fairfax Hospital Department of Surgery

Falls Church, Virginia, 22042, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Imatinib Mesylate; Panitumumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

This is a pilot study utilizing only a small sample size of people.

Results Point of Contact

• Title: Emanuel Petricoin
• Organization: George Mason University

epetrico@gmu.edu

571-830-4166

Study Officials

• Kirsten Edmiston, MD, FACS

  Inova Fairfax Hospital Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: March 19, 2009
• First Posted: March 23, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 30, 2020
• Results First Posted: September 9, 2019

Record last verified: 2016-06

Locations

US (2)