Trial Outcomes & Findings for Evaluation of Metformin, Targeting Cancer Stem Cells for Prevention of Relapse in Gynecologic Patients (NCT NCT01579812)
NCT ID: NCT01579812
Last Updated: 2018-05-25
Results Overview
Determine the percentage of patients alive without recurrence at 18 months. Investigators will also determine recurrence free survival when patients with persistent disease are excluded. Definition of progression or recurrence and survival will be defined as increasing clinical, radiological or histological evidence of disease since study entry or two serum values of CA-125 greater than or equal to two times the upper limits of normal (ULN) performed at least one week apart, regardless of CT scan results. Recurrence-Free Interval will be defined as date from start of chemotherapy to the date of first clinical, biochemical, or radiological evidence of progression or death due to any cause.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
90 participants
Primary outcome timeframe
18 months
Results posted on
2018-05-25
Participant Flow
Participant milestones
| Measure |
Metformin
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
|---|---|
|
Overall Study
STARTED
|
90
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
52
|
Reasons for withdrawal
| Measure |
Metformin
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
|---|---|
|
Overall Study
Ineligible after treatment start
|
40
|
|
Overall Study
Patient choice
|
3
|
|
Overall Study
Noncompliance
|
3
|
|
Overall Study
Withdrawal by Subject
|
6
|
Baseline Characteristics
Evaluation of Metformin, Targeting Cancer Stem Cells for Prevention of Relapse in Gynecologic Patients
Baseline characteristics by cohort
| Measure |
Metformin
n=90 Participants
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
|---|---|
|
Age, Continuous
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
90 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
69 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 monthsPopulation: 90 patients were enrolled, only 38 completed treatment and were analyzed. Patients found to have persistent disease were censored at the time they were found to have progressive disease. 11 patients had persistent disease.
Determine the percentage of patients alive without recurrence at 18 months. Investigators will also determine recurrence free survival when patients with persistent disease are excluded. Definition of progression or recurrence and survival will be defined as increasing clinical, radiological or histological evidence of disease since study entry or two serum values of CA-125 greater than or equal to two times the upper limits of normal (ULN) performed at least one week apart, regardless of CT scan results. Recurrence-Free Interval will be defined as date from start of chemotherapy to the date of first clinical, biochemical, or radiological evidence of progression or death due to any cause.
Outcome measures
| Measure |
Metformin - All Patients Analyzed
n=38 Participants
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
Metformin - Patients With Persistent Disease Excluded
n=27 Participants
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
Patients with persistent disease were excluded in this analysis.
|
Metformin - Patients With Stage IV Ovarian Cancer
Patients with stage IV ovarian cancer receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
|
|---|---|---|---|
|
Recurrence-Free Survival
|
58.1 percentage of patients
Interval 38.0 to 73.8
|
55.6 percentage of patients
Interval 35.2 to 71.8
|
—
|
SECONDARY outcome
Timeframe: Up to 3 YearsPopulation: 90 patients were enrolled and only 38 patients completed treatment. 25 of the 38 patients had stage IIc/III ovarian cancer. 13 of the 38 patients had stage IV ovarian cancer.
Determine the median overall survival time for all patients who complete treatment as well as for patients presenting with stage IIc/ III and stage IV ovarian cancer.
Outcome measures
| Measure |
Metformin - All Patients Analyzed
n=38 Participants
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
Metformin - Patients With Persistent Disease Excluded
n=25 Participants
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
Patients with persistent disease were excluded in this analysis.
|
Metformin - Patients With Stage IV Ovarian Cancer
n=13 Participants
Patients with stage IV ovarian cancer receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
|
|---|---|---|---|
|
Overall Survival
|
43 months
Interval 35.0 to 56.0
|
52 months
Interval 35.0 to 65.0
|
36 months
Interval 15.0 to 43.0
|
Adverse Events
Metformin
Serious events: 26 serious events
Other events: 40 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Metformin
n=90 participants at risk
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
6/90 • Number of events 6 • Up to 30 days post treatment
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Asystole
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Heart failure
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Sick sinus syndrome
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Supraventricular tachycardia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Ascites
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Gastric ulcer
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Ileus
|
6.7%
6/90 • Number of events 6 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.2%
2/90 • Number of events 3 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Upper gastrointestinal hemorrhage
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
General disorders
Non-cardiac chest pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Infections and infestations
Lung infection
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Infections and infestations
Sepsis
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Infections and infestations
Wound infection
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Investigations
Neutrophil count decreased
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Investigations
Platelet count decreased
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Investigations
White blood cell decreased
|
3.3%
3/90 • Number of events 4 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
3.3%
3/90 • Number of events 4 • Up to 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Nervous system disorders
Ischemia cerebrovascular
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Nervous system disorders
Syncope
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Psychiatric disorders
Anxiety
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Renal and urinary disorders
Acute kidney injury
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Vascular disorders
Hypotension
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Vascular disorders
Thromboembolic event
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
Other adverse events
| Measure |
Metformin
n=90 participants at risk
Metformin: Patients receiving primary surgical debulking followed by adjuvant chemotherapy will initiate metformin prior to primary surgery. Following surgery patients will be initiated on metformin prior to the initiation of chemotherapy.
Patients treated with neoadjuvant chemotherapy will be initiated on metformin prior to the initiation of chemotherapy. Following surgery patients will be initiated on metformin prior to the re-initiation of chemotherapy.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
28.9%
26/90 • Number of events 70 • Up to 30 days post treatment
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Palpitations
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Sick sinus syndrome
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Cardiac disorders
Sinus tachycardia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
8.9%
8/90 • Number of events 8 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Bloating
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Constipation
|
3.3%
3/90 • Number of events 3 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Diarrhea
|
14.4%
13/90 • Number of events 19 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Ileus
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Mucositis oral
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Nausea
|
13.3%
12/90 • Number of events 13 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Oral pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Rectal pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Stomach pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Gastrointestinal disorders
Vomiting
|
7.8%
7/90 • Number of events 7 • Up to 30 days post treatment
|
|
General disorders
Chills
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
General disorders
Edema limbs
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
General disorders
Fatigue
|
18.9%
17/90 • Number of events 21 • Up to 30 days post treatment
|
|
General disorders
Fever
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
General disorders
Infusion related reaction
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
General disorders
Non-cardiac chest pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
General disorders
Pain
|
4.4%
4/90 • Number of events 5 • Up to 30 days post treatment
|
|
Immune system disorders
Allergic reaction
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Infections and infestations
Nail infection
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Infections and infestations
Otitis media
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Infections and infestations
Papulopustular rash
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Infections and infestations
Urinary tract infection
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Infections and infestations
Wound infection
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Injury, poisoning and procedural complications
Fall
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Investigations
Alanine aminotransferase increased
|
6.7%
6/90 • Number of events 7 • Up to 30 days post treatment
|
|
Investigations
Alkaline phosphatase increased
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Investigations
Aspartate aminotransferase increased
|
8.9%
8/90 • Number of events 10 • Up to 30 days post treatment
|
|
Investigations
Creatinine increased
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Investigations
Lymphocyte count decreased
|
1.1%
1/90 • Number of events 2 • Up to 30 days post treatment
|
|
Investigations
Neutrophil count decreased
|
13.3%
12/90 • Number of events 17 • Up to 30 days post treatment
|
|
Investigations
Platelet count decreased
|
14.4%
13/90 • Number of events 28 • Up to 30 days post treatment
|
|
Investigations
Weight loss
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Investigations
White blood cell decreased
|
18.9%
17/90 • Number of events 34 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Alkalosis
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
6.7%
6/90 • Number of events 6 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
3.3%
3/90 • Number of events 3 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.8%
7/90 • Number of events 10 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
3.3%
3/90 • Number of events 3 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
1.1%
1/90 • Number of events 2 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.7%
6/90 • Number of events 7 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.6%
5/90 • Number of events 9 • Up to 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.2%
2/90 • Number of events 3 • Up to 30 days post treatment
|
|
Nervous system disorders
Concentration impairment
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Nervous system disorders
Dizziness
|
3.3%
3/90 • Number of events 4 • Up to 30 days post treatment
|
|
Nervous system disorders
Headache
|
3.3%
3/90 • Number of events 3 • Up to 30 days post treatment
|
|
Nervous system disorders
Paresthesia
|
3.3%
3/90 • Number of events 3 • Up to 30 days post treatment
|
|
Nervous system disorders
Peripheral motor neuropathy
|
6.7%
6/90 • Number of events 6 • Up to 30 days post treatment
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
10.0%
9/90 • Number of events 10 • Up to 30 days post treatment
|
|
Psychiatric disorders
Anxiety
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Psychiatric disorders
Depression
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Psychiatric disorders
Insomnia
|
3.3%
3/90 • Number of events 3 • Up to 30 days post treatment
|
|
Psychiatric disorders
Restlessness
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Renal and urinary disorders
Cystitis noninfective
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Renal and urinary disorders
Renal and urinary disorders
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Renal and urinary disorders
Urinary incontinence
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Renal and urinary disorders
Urinary tract pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Reproductive system and breast disorders
Dyspareunia
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Reproductive system and breast disorders
Vaginal pain
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.1%
1/90 • Number of events 2 • Up to 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.1%
1/90 • Number of events 2 • Up to 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.6%
5/90 • Number of events 7 • Up to 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
4.4%
4/90 • Number of events 4 • Up to 30 days post treatment
|
|
Vascular disorders
Hot flashes
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
|
Vascular disorders
Hypotension
|
1.1%
1/90 • Number of events 1 • Up to 30 days post treatment
|
|
Vascular disorders
Thromboembolic event
|
2.2%
2/90 • Number of events 2 • Up to 30 days post treatment
|
Additional Information
Dr. Ronald Buckanovich, MD, PhD
UPMC Hillman Cancer Center
Phone: 412-641-4721
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place