Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00379197
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 82
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Naltrexone may fight breast cancer by blocking the use of estrogen by the tumor cells. Naltrexone may also stop the growth of breast cancer by impairing blood flow to the tumor.

PURPOSE: This phase II trial is studying how well naltrexone works in treating women with metastatic breast cancer that is no longer responsive to previous hormone therapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: naltrexone; Procedure: PET scan	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of naltrexone in women with hormone-refractory, metastatic breast cancer as measured by serial fludeoxyglucose F 18 positron emission tomography-CT scans.

Secondary

• Determine the safety of naltrexone in these patients.

• Determine the median time to event (first time when maximum specific uptake values is higher than that at baseline) within 1 year of study entry.

OUTLINE: This is an open-label study.

Patients receive oral naltrexone once daily for 8 weeks in the absence of disease progression or unacceptable toxicity. After 8 weeks, patients may continue naltrexone off study at the discretion of the physician.

Patients undergo fludeoxyglucose F 18 positron emission tomography-CT scans at baseline, week 4, week 8, and periodically thereafter.

After completion of study treatment, patients are followed for up to 1 year.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Naltrexone for the Treatment of Hormone-Refractory, Metastatic Breast Cancer
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Naltrexone Naltrexone 50 mg will be taken orally once a day every day of a 28 day treatment course (cycle 1) and continue for another identical 28 day treatment (cycle 2) . PET scan will be performed after cycle 1 and cycle 2 complete.

Drug: naltrexone; Naltrexone 50 mg will be orally taken once daily for 28 day (cycle 1), and continues once daily for another 28 days (cycle 2) without interval.; Other Names: REVIA ; Procedure: PET scan; Patients will receive PET scan approximately one hour after being injected with 2-Deoxy-2-[18F]fluoro-D-Glucose (FDG). PET scans will be performed after the completion of cycle 1 and cycle 2 and during the 1 year follow-up.; Other Names: Positron-emission tomography scan

Outcome Measures

Primary Outcome Measures

1. Disease Response [Week 4]

   A response is the number of participants whose tumor demonstrated a decrease in FDG uptake (SUV) by 50% or greater in at least one of the metastatic sites as measured by PET imaging at the end of 4 weeks of treatment compared to baseline.

Secondary Outcome Measures

1. Median Time to Event [From Baseline to 1 Year]

   First time when maximum SUV is higher than that at baseline within 1 year of study entry.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Metastatic, hormone-receptor positive breast cancer

• Disease that has progressed despite previous systemic hormonal therapy. Hormone therapy must be terminated at least 2 weeks prior to study enrollment.

• Prior chemotherapy, immunotherapy, or biological therapy is allowed if at least 3 weeks since last treatment. Patient must recover from the acute toxic effects of the treatment prior to study enrollment.

• Measurable disease as defined by solid tumor response (RECIST) criteria or non-measurable bone disease that is Positron-emission tomography (PET) avid

• Karnofsky performance status >70%

• Female, age 18 years or older

• Adequate organ function within 14 days of study enrollment including the following:

• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.5 x 10^{9/L, platelets >75 x 10}9/L, and hemoglobin > 8 g/dL

• Hepatic: bilirubin ≤ 2 times the upper limit of normal (× ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2 × ULN. (AST and ALT ≤ 5 × ULN is acceptable if liver has tumor involvement)

• Renal: creatinine ≤ 2 times the upper limit of normal

• Women of childbearing potential are required to use an effective method of contraception (ie, a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after the last dose of study drug.

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion criteria:

• Brain metastases unless stable for 1 month or more following radiation therapy.

• Pregnant or lactating women. PET-CT is not approved during pregnancy. A negative urine or serum pregnancy test is required for all females of child bearing potential within 7 days prior to study entry. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

• Use of any short-acting or long-acting opioid medication (including morphine, meperidine, oxycodone, hydromorphone, hydrocodone, fentanyl, tramadol) within 10 days prior to study enrollment

• Pain uncontrolled with the use of non-narcotic drugs (acetaminophen or non-steroidal medications)

• History of sensitivity to naltrexone

• Acute hepatitis or liver failure

• Immunosuppressive therapy for patients with autoimmune diseases, organ transplant, or other indications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Douglas Yee, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00379197
• Other Study ID Numbers: 2006LS016; UMN-0604M85308
• First Posted: Sep 21, 2006
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: stage IV breast cancer, estrogen receptor positive; recurrent breast cancer; hormone-refractory, metastatic breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Naltrexone
Arm/Group Description	Naltrexone 50 mg taken orally once daily for 2 28-day cycles with an option to continue on Naltrexone at the discretion of the treating physician.
Period Title: Overall Study
STARTED	13
COMPLETED	8
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Naltrexone
Arm/Group Description	Naltrexone hydrochloride 50 mg will be taken once a day every day of a 28 day treatment course. Positron-emission tomography (PET) / computed tomography (CT) given with injection of 2-Deoxy-2-[18F]fluoro-D-Glucose (FDG). naltrexone hydrochloride: Naltrexone should be taken with water or food, and it can be taken at any time day. Naltrexone 50 mg will be taken once a day every day of a 28 day treatment course. Positron-emission tomography (PET) / computed tomography (CT): Given with injection of 2-Deoxy-2-[18F]fluoro-D-Glucose (FDG). Follow-up scans will be performed after the completion of cycle 1 and cycle 2 and during the 1 year follow-up.
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 50%
>=65 years	4 50%
Sex/Gender, Customized (participants) [Number]
Female only	8 100%
Region of Enrollment (participants) [Number]
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Disease Response
Description	A response is the number of participants whose tumor demonstrated a decrease in FDG uptake (SUV) by 50% or greater in at least one of the metastatic sites as measured by PET imaging at the end of 4 weeks of treatment compared to baseline.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Naltrexone Treatment
Arm/Group Description	Naltrexone 50 mg will be orally taken once daily for 28 day (cycle 1), and continues once daily for another 28 days (cycle 2) without interval. PET scan will be performed as baseline level at the beginning of study and after the completion of cycle 1 and cycle 2.
Measure Participants	8
Number [participants]	1 12.5%

2. Secondary Outcome

Title	Median Time to Event
Description	First time when maximum SUV is higher than that at baseline within 1 year of study entry.
Time Frame	From Baseline to 1 Year

Outcome Measure Data

Analysis Population Description

One of the 8 participants did not have an increase in SUV above baseline at 8 weeks, but no further PET scans were performed after 8 weeks. The reported median value is for the remaining 7 participants.

Arm/Group Title	Naltrexone
Arm/Group Description	Naltrexone 50 mg will be taken orally once a day every day of a 28 day treatment course (cycle 1) and continue for another identical 28 day treatment (cycle 2) . PET scan will be performed after cycle 1 and cycle 2 complete. naltrexone: Naltrexone 50 mg will be orally taken once daily for 28 day (cycle 1), and continues once daily for another 28 days (cycle 2) without interval. PET scan: Patients will receive PET scan approximately one hour after being injected with 2-Deoxy-2-[18F]fluoro-D-Glucose (FDG). PET scans will be performed after the completion of cycle 1 and cycle 2 and during the 1 year follow-up.
Measure Participants	7
Median (Full Range) [weeks]	8

Adverse Events

Arm/Group Title	Naltrexone Treatment
Arm/Group Description	Naltrexone 50 mg will be orally taken once daily for 28 day (cycle 1), and continues once daily for another 28 days (cycle 2) without interval. PET scan will be performed after the completion of cycle 1 and cycle 2 and during the 1 year follow-up compared to the baseline level of FDG uptake.
All Cause Mortality
	Naltrexone Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Naltrexone Treatment
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Naltrexone Treatment
	Affected / at Risk (%)	# Events
Total	4/8 (50%)
Blood and lymphatic system disorders
Anemia	1/8 (12.5%)
Pain right axillary node	1/8 (12.5%)
Pancytopenia	1/8 (12.5%)
Cardiac disorders
Palpitations	1/8 (12.5%)
Gastrointestinal disorders
Abdominal bloating	1/8 (12.5%)
right upper quadrant abdominal pain	1/8 (12.5%)
increased thirst	1/8 (12.5%)
Ascites	1/8 (12.5%)
Nausea	1/8 (12.5%)
Hepatobiliary disorders
Cirrhotic Appearing Liver	1/8 (12.5%)
Investigations
Weight Gain	1/8 (12.5%)
Musculoskeletal and connective tissue disorders
pain - muscular	1/8 (12.5%)
Psychiatric disorders
Insomnia	1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Shortness of breath	1/8 (12.5%)
cough	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Itching	1/8 (12.5%)
mild erythema	1/8 (12.5%)
hand and foot syndrome	1/8 (12.5%)
Vascular disorders
Hot Flashes	1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.