- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01939483
A Pilot Study of Irinotecan in Patients With Breast Cancer and CNS Metastases
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES; I. To evaluate the safety and efficacy of irinotecan (irinotecan hydrochloride) in breast cancer patients with brain metastases who progressed after radiation therapy.
II. To estimate central nervous system (CNS) objective response and clinical benefit rate in patients with breast cancer and brain metastases treated with irinotecan.
III. To estimate progression free survival. IV. To estimate overall survival. V. To assess the toxicity of Irinotecan.
OUTLINE:
Patients receive irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1, 8, 15, 22, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for up to 24 months.
Study Type
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of breast cancer (irrespective of receptor status), with evidence of CNS disease by computed tomography (CT) or magnetic resonance imaging (MRI), who have progressed after whole brain radiation therapy or stereotactic radiosurgery
- Patients must not be a candidate for surgical resection and/or further stereotactic radiosurgery
- Patients may have had an unlimited number of prior treatments, including any systemic chemotherapy (excluding prior progression of disease with topoisomerase inhibitors as explained below), surgical resection, whole brain radiation, stereotactic radiosurgery, or radioimmunotherapy
- Patient must have MRI of brain obtained within two weeks of study initiation for staging and patients must also receive first dose within two weeks of study enrollment
- Patients must have at least one measurable brain lesion prior to start of treatment (≥ 10 mm on T1-weighted, gadolinium-enhanced MRI)
- Karnofsky performance score greater than 60
- At least two weeks must have elapsed since prior chemotherapy, three weeks must have elapsed since last surgery, and six weeks since completion of radiation therapy
- Hemoglobin > 9
- Absolute neutrophil count (ANC) > 1500
- Platelet count (plt) > 125
- Creatinine < 1.5
- Total bilirubin < 1.5
- Aspartate aminotransferase and alanine aminotransferase levels within five times the upper limit of normal
- Patients may be on oral corticosteroids at stable dose (no dose change within two weeks of enrollment), and may be on antiepileptic medication (except for cytochrome P450 3A4 (CYP3A4) enzyme-inducing antiepileptic medications)
- Fertile patients must use effective contraception
Exclusion Criteria:
- Pregnancy, lactation, immunosuppression other than corticosteroids
- Patient may be on hormonal therapy or Herceptin, but no other concurrent chemotherapy is allowed
- Patients who had progression of their breast cancer after prior administration of irinotecan are excluded
- Patients with leptomeningeal carcinomatosis as the only site of CNS involvement are excluded
- No other active malignancy except for any of the following: curatively treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, other malignancies considered disease-free
- Patients using valproic acid within the last two weeks and patients with contraindications to anticholinergic agents will be excluded
- Concurrent administration of CYP3A4 enzyme-inducing antiepileptic medications (e.g. phenytoin) will not be allowed (if patients are taking one of these agents, they must switch to a non- enzyme-inducing antiepileptic medication prior to start of treatment)
- No history of immediate or delayed-type hypersensitivity reaction to gadolinium contrast agents or other contraindication to gadolinium contrast, and no other known contraindication to MRI
- Homozygous for uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele * All patients will be tested for UGT1A genotype prior to starting treatment and be excluded if they are homozygous for the UGT1A1*28 allele (UGT1A1 7/7 genotype); irinotecan's active metabolite glucuronidation of 7-ethyl-10-hydroxycamptothecin (SN-38) is inactivated through glucuronidation by uridine diphosphate glucuronosyltransferases (UGTs) mainly in the liver and is excreted through the bile ducts; a meta-analysis demonstrated that the UGT1A1*28 genotype is moderately predictive of severe irinotecan induced hematologic toxicity at moderate doses and strongly predictive at high doses, and in 2005, the Food and Drug Administration (FDA) added a warning to the irinotecan packaging label that patients with the UGT1A1*28 genotype were at increased risk for neutropenia
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (irinotecan hydrochloride)
Patients receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, 15, 22, and 29. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. This arm also includes laboratory biomarker analysis as an intervention. |
Correlative studies
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
CNS objective response (complete response or partial response), defined as at least 20% volumetric reduction of CNS lesions in absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease, based on MRI
Time Frame: Up to 24 months
|
Up to 24 months
|
Response rate of patients who have remained progression-free, based on MRI
Time Frame: Up to 6 months
|
Up to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Time between treatment initiation and death, assessed up to 24 months
|
The product limit estimator developed by Kaplan and Meier was used to graphically describe the distribution of survival among patients with recurrent disease.
|
Time between treatment initiation and death, assessed up to 24 months
|
Progression free survival (PFS)
Time Frame: Time between treatment initiation and disease progression/relapse/death, assessed up to 24 months
|
The product limit estimator developed by Kaplan and Meier was used to graphically describe the distribution of PFS among patients with recurrent disease.
|
Time between treatment initiation and disease progression/relapse/death, assessed up to 24 months
|
Clinical benefit rate (objective response + stable disease at least 16 weeks)
Time Frame: Up to 24 months
|
Up to 24 months
|
|
Frequency of toxicity occurrence, assessed by National Cancer Institute's Common Terminology Criteria (CTC) for Adverse Events version 4.0
Time Frame: Up to 24 months
|
Tabulated by type, and worst grade experienced by the patient.
Toxicity will initially be summarized within each cohort or patient subgroup, and then collectively summarized.
|
Up to 24 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rita Mehta, MD, University of California, Irvine
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Neoplastic Processes
- Breast Neoplasms
- Neoplasm Metastasis
- Breast Neoplasms, Male
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
- Camptothecin
Other Study ID Numbers
- UCI 11-22
- 2011-8497 (Other Identifier: University of California, Irvine)
- NCI-2013-01136 (Other Identifier: NCI Clinical Trials Reporting Program (CTRP))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Male Breast Cancer
-
Centro Hospitalar Lisboa OcidentalInstituto Nacional de Medicina Legal e Ciências Forenses, Delegação do SulUnknownMale Breast Cancer | Female Breast Cancer
-
University of WashingtonNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast CancerUnited States
-
National Cancer Institute (NCI)CompletedMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)WithdrawnHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast CancerUnited States
-
National Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast CancerUnited States
-
Innocrin PharmaceuticalCompletedBreast Cancer | Advanced Breast Cancer | Metastatic Breast Cancer | Triple Negative Breast Cancer | Male Breast Cancer | ER+ Breast Cancer | Cancer of the BreastUnited States
-
Organon and CoInstitute for Applied Economics and Health Research ApsCompleted
-
German Breast GroupPfizerCompletedMale Breast CancerGermany
-
Salah Azaïz Cancer InstituteUnknownMale Breast CancerTunisia
Clinical Trials on laboratory biomarker analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States