A Pilot Study of Irinotecan in Patients With Breast Cancer and CNS Metastases

Sponsor

University of California, Irvine (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01939483

Collaborator

(none)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

This pilot clinical trial studies irinotecan hydrochloride in treating patients with breast cancer and brain metastases that progressed after whole brain radiation therapy or stereotactic radiosurgery. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Metastases Male Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer	Drug: irinotecan hydrochloride Other: laboratory biomarker analysis	N/A

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.

To estimate central nervous system (CNS) objective response and clinical benefit rate in patients with breast cancer and brain metastases treated with irinotecan.
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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study of Irinotecan in Patients With Breast Cancer and CNS Metastases

Study Start Date :

Dec 1, 2012

Anticipated Primary Completion Date :

Aug 1, 2017

Anticipated Study Completion Date :

Aug 1, 2018

Arms and Interventions

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.	Drug: irinotecan hydrochloride Given IV Other Names: Campto Camptosar camptothecin-11 CPT-11 irinotecan irinotecan HCl U-101440E Other: laboratory biomarker analysis Correlative studies

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.

Drug: irinotecan hydrochloride

Given IV

Other Names:

Campto

Camptosar

camptothecin-11

CPT-11

irinotecan

irinotecan HCl

U-101440E

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

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 [Up to 24 months]
Response rate of patients who have remained progression-free, based on MRI [Up to 6 months]

Secondary Outcome Measures

Overall survival [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.
Progression free survival (PFS) [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.
Clinical benefit rate (objective response + stable disease at least 16 weeks) [Up to 24 months]
Frequency of toxicity occurrence, assessed by National Cancer Institute's Common Terminology Criteria (CTC) for Adverse Events version 4.0 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 UGT1A128 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 UGT1A128 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 UGT1A128 genotype were at increased risk for neutropenia