Panitumumab and Chemotherapy in Patients With Advanced Colorectal Cancer After Prior Therapy With Bevacizumab

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Ohio State University Comprehensive Cancer Center
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Christina Wu, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01814501
First received: February 25, 2013
Last updated: September 11, 2013
Last verified: September 2013
  Purpose

This phase II trial studies how well panitumumab and combination chemotherapy works in treating patients with metastatic colorectal cancer previously treated with combination chemotherapy and bevacizumab. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving panitumumab and combination chemotherapy together may kill more tumor cells


Condition Intervention Phase
Mucinous Adenocarcinoma of the Colon
Mucinous Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Signet Ring Adenocarcinoma of the Colon
Signet Ring Adenocarcinoma of the Rectum
Stage IV Colon Cancer
Stage IV Rectal Cancer
Biological: panitumumab
Drug: irinotecan hydrochloride
Drug: fluorouracil
Drug: leucovorin calcium
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Panitumumab in Combination With FOLFIRI After Progression on FOLFIRI Plus Bevacizumab in KRAS(Kirsten Rat Sarcoma) Wild-Type Metastatic Colorectal Cancer.

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Progression free survival(PFS) [ Time Frame: Time from study day 1 to the time the patient is first recorded as having disease progression or death, assessed up to 2 years ] [ Designated as safety issue: No ]
    Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Estimated using the Kaplan-Meier estimator with confidence interval calculated based on the Brookmeyer-Crowley method.


Secondary Outcome Measures:
  • Frequency and severity of toxicities of the regimens, graded according to the NCI CTCAE v4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Frequencies will be computed for discrete data.

  • Overall response rate, as described in RECIST v1.1 criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Time from study day 1 to the date of death or the last date the patient was known to be alive, assessed up to 1 year ] [ Designated as safety issue: No ]
    Continuous variables will be expressed by means, standard deviations and 95% confidence intervals. Kaplan-Meier estimator will be used.


Estimated Enrollment: 35
Study Start Date: February 2013
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (panitumumab, combination chemotherapy)
5-Fluorouracil, irinotecan, and panitumumab
Biological: panitumumab
Given IV
Other Names:
  • ABX-EGF
  • MOAB ABX-EGF
  • monoclonal antibody ABX-EGF
  • Vectibix
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the median progression-free survival in patients treated with leucovorin calcium, fluorouracil, and irinotecan hydrochloride (FOLFIRI) and panitumumab for K-ras wild-type, metastatic colorectal carcinoma who have already progressed on FOLFIRI + Bevacizumab.

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of toxicities of the regimens. II. To determine overall response rate. III. To determine the median overall survival and the overall survival rate at 1 year.

OUTLINE:

Patients receive panitumumab intravenously (IV) over 60-90 minutes, leucovorin calcium IV over 90 minutes, fluorouracil IV continuously over 46 hours, and irinotecan hydrochloride IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

  Eligibility

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

Inclusion Criteria:

  • Patients with advanced adenocarcinoma of the colon or rectum not curable with surgery or radiotherapy and have been previously treated for their disease with FOLFIRI plus bevacizumab in the first line metastatic setting; patients will only be eligible if their last line of therapy prior to enrolling onto the study was FOLFIRI and bevacizumab received no more than 6 months prior to enrolling in this study; they should have been treated with FOLFIRI plus bevacizumab until disease progression is radiographically documented
  • Patients' tumors will need to tested for the K-RAS mutation status; only those patients with wild-type or unmutated K-RAS oncogene are eligible to participate in this study
  • Provide written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
  • Prior cetuximab is allowed in the adjuvant but not in the metastatic setting, but must have been completed at least 6 months before starting this trial
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Life expectancy greater than 12 weeks
  • No active brain metastasis; previously surgically treated or irradiated lesions are allowed if not clinically active
  • Has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential)
  • Ability to understand and willingness to sign a written informed consent
  • No history of severe reactions to fluorouracil (5-FU), irinotecan (irinotecan hydrochloride), or a monoclonal antibody
  • Leukocytes >= 3000/uL
  • Absolute neutrophil count >= 1500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9 mg/dL
  • Total bilirubin =< 1.5 X upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 X ULN (or < 5 x ULN with liver metastases)
  • Creatinine clearance (CrCl) >= 30 ml/min (Cockroft-Gault equation)
  • Magnesium >= lower limit of normal
  • Measurable disease is required according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • The effects of Panitumumab on the developing human fetus are unknown; for this reason and because monoclonal antibodies as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and up to 6 months after completing therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria:

  • Pregnant or lactating women; women of childbearing potential with either a positive or no pregnancy test at baseline; woman or men of childbearing potential not using a reliable and appropriate contraceptive method; (postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential)
  • Sexually active males unwilling to practice contraception during the study and 6 months beyond
  • Uncontrolled intercurrent illness including but not limited to clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias) or myocardial infarction within the last 12 months, and serious concurrent infections
  • History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
  • KRAS mutant tumors
  • Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as >= Common Toxicity Criteria [CTC] grade 2 [Common Terminology Criteria for Adverse Events (CTCAE) version 4.0])
  • Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =< 1 year
  • Bevacizumab within the last 4 weeks before starting treatment on trial
  • Patient is more than 6 months since the last dose of FOLFIRI
  • Patients who have required toxicity related dose reductions of no less than 50% of the original dose of infusional 5-FU and/or irinotecan during the administration of FOLFIRI + bevacizumab
  • Prior exposure to panitumumab in any setting
  • Prior exposure to cetuximab in the metastatic (stage IV) setting
  • Radiotherapy =< 14 days prior to enrollment; patients must have recovered from all radiotherapy-related toxicities
  • Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, leucovorin (leucovorin calcium), irinotecan, or panitumumab
  • Treatment for other carcinomas within the last three years, except cured non-melanoma skin and treated in-situ cervical cancer
  • Participation in any investigational drug study within 4 weeks preceding the start of study treatment
  • Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
  • Major surgery within 4 weeks of the start of study treatment, without complete recovery
  • Unwillingness to give written informed consent
  • Unwillingness to participate or inability to comply with the protocol for the duration of the study
  • Patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and those severely immunocompromised will be excluded; however, no patients will be tested for HIV
  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: NCT01814501

Contacts
Contact: Ohio State University Comprehensive Cancer Center 1-800-293-5066 Jamesline@osumc.edu
Contact: Christina Wu, MD 614-293-6529 Christina.Wu@osumc.edu

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Christina Wu    614-293-9863    Christina.Wu@osumc.edu   
Principal Investigator: Christina Wu         
Sub-Investigator: Richard Goldberg, MD         
Sub-Investigator: Tony Saab, MD         
Sub-Investigator: Ahmed Ghany, MD         
Sponsors and Collaborators
Christina Wu
Amgen
Investigators
Principal Investigator: Christina Wu Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Christina Wu, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01814501     History of Changes
Other Study ID Numbers: OSU-11131, NCI-2013-00432
Study First Received: February 25, 2013
Last Updated: September 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
Metastatic colon cancer

Additional relevant MeSH terms:
Cystadenocarcinoma
Adenocarcinoma
Colonic Neoplasms
Rectal Neoplasms
Adenocarcinoma, Mucinous
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Cystic, Mucinous, and Serous
Antibodies, Monoclonal
Fluorouracil
Irinotecan
Bevacizumab
Camptothecin
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014