Megestrol Acetate With or Without Mirtazapine in Treating Cancer Patients With Weight Loss or Loss of Appetite
Primary Purpose
Anorexia
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Megestrol Acetate
Mirtazapine
Sponsored by
About this trial
This is an interventional supportive care trial for Anorexia
Eligibility Criteria
Inclusion Criteria:
- Patient must have a histologically or cytologically confirmed solid malignancy
- Patient must be >=18 years old.
- Patient must have shown unintentional weight loss of >= 5% in 6 weeks dating back from time of consent or >= 10% in 6 months dating back from time of consent
- Patient must have a poor appetite (defined as a score of =< 14 on the Simplified Nutritional Appetite Questionnaire (SNAQ)
- Prior diagnostic or therapeutic surgery is allowed as long as the wound has fully healed, the patient has fully recovered from the procedure, and at least 4 weeks have elapsed from the procedure; for needle or core biopsy, or minimally invasive procedures such as chest tube placement, this 4-week recovery period does not apply, but the patient must have recovered fully from the procedure
- Concomitant administration of chemotherapy is permitted but not required
- Prior radiation therapy is allowed for local symptom palliation prior to the start of treatment as long as at least 2 weeks have elapsed from the procedure and the patient has fully recovered from treatment-related toxicities
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patient must have normal organ and marrow function as defined below:
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- Patient must be able to understand and willing to sign a written informed consent document
Exclusion Criteria:
- Patient must not be receiving any other investigational agents
- Patient must not be receiving any tube feeds or parenteral nutrition
- Patient must not be taking either MA or MRZ within 4 weeks prior to enrolling on the study, prior use of either MA or MRZ more than 4 weeks before enrollment is allowed
- Patient must not be taking any medication for appetite stimulation within 4 weeks prior to enrolling on the study; prior use of an appetite stimulant more than 4 weeks before enrollment is allowed
- Patient must not have a known seizure disorder
- Patient must not have received abdominal radiation within 4 weeks of enrolling on the study; patients who have received abdominal radiation more than 4 weeks prior to enrollment may participate in the study, as long as they have recovered from toxicities of radiation therapy
- Patient must not be taking chronic systemic corticosteroids (e.g., prednisone, dexamethasone) within the 4 weeks prior to study entry or while on study (unless as pre-medication for chemotherapy)
- Patient must not have moderate to severe depression defined as score of >= 20 on the Center for Epidemiologic Studies Depression Scale (CES-D)
- Patient must not be taking any anti-depressant therapy within the 4 weeks prior to study entry
- Patient must not be on antipsychotic therapy such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone for 30 days prior to study; patient may receive prochlorperazine or other phenothiazines as antiemetic therapy
- Patient must not have a history of phenylketonuria (MRZ compounds contain phenylalanine)
- Patient must not have active dysphagia or gastrointestinal tract obstruction
- Patient must not have a previous history of deep venous thrombosis, pulmonary embolism, or thrombophlebitis
- Patient must not be receiving any other agent to increase appetite or weight such as growth hormone (GH), insulin-like growth factor (IGF-1), growth hormone-releasing hormone, insulin-like growth factor binding protein-3 (IGFBP-3), or cannabinoids within the 6 weeks prior to study entry
- Patient must not have a body mass index (BMI) > 30
- Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MA or MRZ
- Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Mirtazapine can cause non-teratogenic adverse effects on the developing human fetus at the recommended therapeutic dose; for this reason and because MA as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women of childbearing potential must have a negative pregnancy test prior to study entry
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A (megestrol alone)
Arm B (megestrol plus mirtazapine)
Arm Description
Megestrol acetate 800 mg PO daily x 8 weeks
Megestrol acetate 800 mg PO daily x 8 weeks Mirtazapine 15 mg PO at bedtime x 1 week followed by 30 mg PO at bedtime x 7 weeks
Outcomes
Primary Outcome Measures
Response rates for weight gain
Determine the rates of >= 5% weight gain in the treatment groups. Compare the difference of the response rate between the 2 groups.
Secondary Outcome Measures
Safety and tolerability of MA alone and MA + MRZ
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Weight change (in lbs)
Change over time as well as the difference between groups for weight (in lbs) will be analyzed.
Appetite stimulation
Assessed using Simplified Nutritional Appetite Questionnaire (SNAQ). The change over time as well as the difference between groups will be analyzed.
Quality of life
Assessed using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The Change over time as well as the difference between groups will be analyzed.
Mood assessments
Measured using CES-D. The Change over time as well as the difference between groups will be analyzed.
Evaluation of biochemical markers
Explore the relationship between weight gain and serum markers of nutritional status (prealbumin, transferrin, C-reactive protein, TNF-alpha, and IL-1 and IL-6).
Full Information
NCT ID
NCT01501396
First Posted
December 20, 2011
Last Updated
January 31, 2014
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT01501396
Brief Title
Megestrol Acetate With or Without Mirtazapine in Treating Cancer Patients With Weight Loss or Loss of Appetite
Official Title
Treatment of Cancer Anorexia-cachexia Syndrome (CACS) With Mirtazapine and Megestrol Acetate
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Withdrawn
Study Start Date
September 2013 (undefined)
Primary Completion Date
September 2015 (Anticipated)
Study Completion Date
September 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This randomized phase II trial studies the safety and efficacy of megestrol acetate given with or without mirtazapine in treating cancer patients with weight loss and loss of appetite. To date, no pharmacologic interventions have been approved by FDA to treat cancer anorexia-cachexia syndrome (CACS). Megestrol acetate has been shown to increase appetite in cancer patients. Adding mirtazapine may provide a much more effective treatment and help improve quality of life.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anorexia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (megestrol alone)
Arm Type
Experimental
Arm Description
Megestrol acetate 800 mg PO daily x 8 weeks
Arm Title
Arm B (megestrol plus mirtazapine)
Arm Type
Experimental
Arm Description
Megestrol acetate 800 mg PO daily x 8 weeks
Mirtazapine 15 mg PO at bedtime x 1 week followed by 30 mg PO at bedtime x 7 weeks
Intervention Type
Drug
Intervention Name(s)
Megestrol Acetate
Other Intervention Name(s)
BDH 1298, Maygace, Megace, Megestil, Niagestin, Pallace
Intervention Type
Drug
Intervention Name(s)
Mirtazapine
Other Intervention Name(s)
Remeron
Primary Outcome Measure Information:
Title
Response rates for weight gain
Description
Determine the rates of >= 5% weight gain in the treatment groups. Compare the difference of the response rate between the 2 groups.
Time Frame
Baseline to 8 weeks
Secondary Outcome Measure Information:
Title
Safety and tolerability of MA alone and MA + MRZ
Description
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Time Frame
Baseline to 12 weeks (30 days after end of study)
Title
Weight change (in lbs)
Description
Change over time as well as the difference between groups for weight (in lbs) will be analyzed.
Time Frame
Baseline to 8 weeks
Title
Appetite stimulation
Description
Assessed using Simplified Nutritional Appetite Questionnaire (SNAQ). The change over time as well as the difference between groups will be analyzed.
Time Frame
Baseline to 8 weeks
Title
Quality of life
Description
Assessed using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The Change over time as well as the difference between groups will be analyzed.
Time Frame
Baseline to 8 weeks
Title
Mood assessments
Description
Measured using CES-D. The Change over time as well as the difference between groups will be analyzed.
Time Frame
Baseline to 8 weeks
Title
Evaluation of biochemical markers
Description
Explore the relationship between weight gain and serum markers of nutritional status (prealbumin, transferrin, C-reactive protein, TNF-alpha, and IL-1 and IL-6).
Time Frame
Baseline to 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient must have a histologically or cytologically confirmed solid malignancy
Patient must be >=18 years old.
Patient must have shown unintentional weight loss of >= 5% in 6 weeks dating back from time of consent or >= 10% in 6 months dating back from time of consent
Patient must have a poor appetite (defined as a score of =< 14 on the Simplified Nutritional Appetite Questionnaire (SNAQ)
Prior diagnostic or therapeutic surgery is allowed as long as the wound has fully healed, the patient has fully recovered from the procedure, and at least 4 weeks have elapsed from the procedure; for needle or core biopsy, or minimally invasive procedures such as chest tube placement, this 4-week recovery period does not apply, but the patient must have recovered fully from the procedure
Concomitant administration of chemotherapy is permitted but not required
Prior radiation therapy is allowed for local symptom palliation prior to the start of treatment as long as at least 2 weeks have elapsed from the procedure and the patient has fully recovered from treatment-related toxicities
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Patient must have normal organ and marrow function as defined below:
Leukocytes >= 3,000/mcL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
Patient must be able to understand and willing to sign a written informed consent document
Exclusion Criteria:
Patient must not be receiving any other investigational agents
Patient must not be receiving any tube feeds or parenteral nutrition
Patient must not be taking either MA or MRZ within 4 weeks prior to enrolling on the study, prior use of either MA or MRZ more than 4 weeks before enrollment is allowed
Patient must not be taking any medication for appetite stimulation within 4 weeks prior to enrolling on the study; prior use of an appetite stimulant more than 4 weeks before enrollment is allowed
Patient must not have a known seizure disorder
Patient must not have received abdominal radiation within 4 weeks of enrolling on the study; patients who have received abdominal radiation more than 4 weeks prior to enrollment may participate in the study, as long as they have recovered from toxicities of radiation therapy
Patient must not be taking chronic systemic corticosteroids (e.g., prednisone, dexamethasone) within the 4 weeks prior to study entry or while on study (unless as pre-medication for chemotherapy)
Patient must not have moderate to severe depression defined as score of >= 20 on the Center for Epidemiologic Studies Depression Scale (CES-D)
Patient must not be taking any anti-depressant therapy within the 4 weeks prior to study entry
Patient must not be on antipsychotic therapy such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone for 30 days prior to study; patient may receive prochlorperazine or other phenothiazines as antiemetic therapy
Patient must not have a history of phenylketonuria (MRZ compounds contain phenylalanine)
Patient must not have active dysphagia or gastrointestinal tract obstruction
Patient must not have a previous history of deep venous thrombosis, pulmonary embolism, or thrombophlebitis
Patient must not be receiving any other agent to increase appetite or weight such as growth hormone (GH), insulin-like growth factor (IGF-1), growth hormone-releasing hormone, insulin-like growth factor binding protein-3 (IGFBP-3), or cannabinoids within the 6 weeks prior to study entry
Patient must not have a body mass index (BMI) > 30
Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MA or MRZ
Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Mirtazapine can cause non-teratogenic adverse effects on the developing human fetus at the recommended therapeutic dose; for this reason and because MA as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; women of childbearing potential must have a negative pregnancy test prior to study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saiama Waqar, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
12. IPD Sharing Statement
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
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Megestrol Acetate With or Without Mirtazapine in Treating Cancer Patients With Weight Loss or Loss of Appetite
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