Trial Outcomes & Findings for Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer (NCT NCT00071058)
NCT ID: NCT00071058
Last Updated: 2012-09-18
Results Overview
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is defined as the disappearance of all signs and symptoms of tumor for a period of at least 4 weeks. Partial response is defined as at least a 30% decrease in the sum of the longest diameter of all measured lesions lasting for a period of 4 weeks.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
50 participants
Primary outcome timeframe
Every 6 weeks for up to a year
Results posted on
2012-09-18
Participant Flow
Participant milestones
| Measure |
Surgery Plus Chemotherapy
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m\^2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Overall Study
STARTED
|
50
|
|
Overall Study
COMPLETED
|
49
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Surgery Plus Chemotherapy
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m\^2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Overall Study
brain tumor-removed from study
|
1
|
Baseline Characteristics
Surgery Plus Chemotherapy (Doxorubicin, Vincristine and Etoposide), Mitotane, and Tariquidar to Treat Adrenocortical Cancer
Baseline characteristics by cohort
| Measure |
Surgery Plus Chemothrapy
n=50 Participants
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
49 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Age Continuous
|
45.56 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
46 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 6 weeks for up to a yearResponse was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is defined as the disappearance of all signs and symptoms of tumor for a period of at least 4 weeks. Partial response is defined as at least a 30% decrease in the sum of the longest diameter of all measured lesions lasting for a period of 4 weeks.
Outcome measures
| Measure |
Surgery Plus Chemotherapy
n=49 Participants
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Percentage of Participants With a Partial or Complete Response
Complete Response
|
4 Percentage of participants
|
|
Percentage of Participants With a Partial or Complete Response
Partial Response
|
6 Percentage of participants
|
SECONDARY outcome
Timeframe: 60 months, 19 daysHere is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Outcome measures
| Measure |
Surgery Plus Chemotherapy
n=49 Participants
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Number of Participants With Adverse Events
|
49 Participants
|
Adverse Events
Surgery Plus Chemothrapy
Serious events: 13 serious events
Other events: 49 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Surgery Plus Chemothrapy
n=50 participants at risk
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
6.0%
3/50 • Number of events 3
|
|
Cardiac disorders
Cardiac left ventricular function
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Cardiac-ischemia/infarction
|
2.0%
1/50 • Number of events 2
|
|
Cardiac disorders
Thrombosis/embolism
|
4.0%
2/50 • Number of events 2
|
|
General disorders
Fatigue (lethargy, malaise, asthenia)
|
2.0%
1/50 • Number of events 1
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
10.0%
5/50 • Number of events 5
|
|
General disorders
Rigors/chills
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Anorexia
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
6.0%
3/50 • Number of events 3
|
|
Gastrointestinal disorders
Dehydration
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea patients without colostomy
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Dysphagia, esophagitis, odynophagia (painful swallowing)
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Ileus (or neuroconstipation)
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
10.0%
5/50 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
6.0%
3/50 • Number of events 3
|
|
Infections and infestations
Febrile Neutropenia
|
4.0%
2/50 • Number of events 2
|
|
Infections and infestations
Infection
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Infection without neutropenia
|
2.0%
1/50 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain or cramping
|
4.0%
2/50 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
2.0%
1/50 • Number of events 1
|
Other adverse events
| Measure |
Surgery Plus Chemothrapy
n=50 participants at risk
Surgical resection can be performed at the time of study entry, when patients have a mixed response, or if their tumors respond to chemotherapy.
Surgical resection will be followed by chemotherapy with 2 grams oral dose daily of mitotane on cycle 1, day 1, 6 mg/m\^2 continuous intravenous infusion doxorubicin over 96 hours days 1-4, 0.18 mg/m2 continuous intravenous infusion vincristine over 96 hours days 1-4, and 36 mg/m\^2 continuous intravenous infusion etoposide over 96 hours days 1-4, and 150 mg tariquidar through central venous catheter over 30 minutes on days 1 and 3.
|
|---|---|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
6.0%
3/50 • Number of events 3
|
|
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
18.0%
9/50 • Number of events 11
|
|
Blood and lymphatic system disorders
Hemoglobin
|
94.0%
47/50 • Number of events 176
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
68.0%
34/50 • Number of events 62
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
90.0%
45/50 • Number of events 101
|
|
Blood and lymphatic system disorders
Platelets
|
66.0%
33/50 • Number of events 109
|
|
Cardiac disorders
Palpitations
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Sinus tachycardia
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Vasovagal episode
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Cardiac left ventricular function
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Edema
|
12.0%
6/50 • Number of events 6
|
|
Cardiac disorders
Hypertension
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Hypotension
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Peripheral arterial ischemia
|
2.0%
1/50 • Number of events 1
|
|
Cardiac disorders
Thrombosis/embolism
|
8.0%
4/50 • Number of events 4
|
|
Blood and lymphatic system disorders
Prothrombin time (PT)
|
2.0%
1/50 • Number of events 1
|
|
General disorders
Fatigue (lethargy, malaise, asthenia)
|
88.0%
44/50 • Number of events 111
|
|
General disorders
Fever
|
24.0%
12/50 • Number of events 13
|
|
General disorders
Rigors, chills
|
2.0%
1/50 • Number of events 1
|
|
General disorders
Sweating (diaphoresis)
|
6.0%
3/50 • Number of events 4
|
|
General disorders
Weight loss
|
22.0%
11/50 • Number of events 15
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
68.0%
34/50 • Number of events 37
|
|
Skin and subcutaneous tissue disorders
Bruising (in absence of grade 3 or 4 thrombocytopenia)
|
4.0%
2/50 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Hand-foot skin reaction
|
6.0%
3/50 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
2.0%
1/50 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pigmentation changes (e.g., vitiligo)
|
2.0%
1/50 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
16.0%
8/50 • Number of events 9
|
|
Endocrine disorders
Hot flashes/flushes
|
8.0%
4/50 • Number of events 6
|
|
Gastrointestinal disorders
Anorexia
|
66.0%
33/50 • Number of events 56
|
|
Gastrointestinal disorders
Constipation
|
56.0%
28/50 • Number of events 45
|
|
Gastrointestinal disorders
Dehydration
|
12.0%
6/50 • Number of events 8
|
|
Gastrointestinal disorders
Diarrhea patients without colostomy
|
56.0%
28/50 • Number of events 56
|
|
Gastrointestinal disorders
Dyspepsia/heartburn
|
16.0%
8/50 • Number of events 9
|
|
Gastrointestinal disorders
Dysphagia, esophagitis, odynophagia (painful swallowing)
|
8.0%
4/50 • Number of events 7
|
|
Gastrointestinal disorders
Flatulence
|
6.0%
3/50 • Number of events 3
|
|
Gastrointestinal disorders
Ileus (or neuroconstipation)
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
84.0%
42/50 • Number of events 91
|
|
Gastrointestinal disorders
Stomatitis/pharyngitis (oral/pharyngeal mucositis)
|
60.0%
30/50 • Number of events 61
|
|
Gastrointestinal disorders
Taste disturbance (dysgeusia)
|
20.0%
10/50 • Number of events 16
|
|
Gastrointestinal disorders
Vomiting
|
60.0%
30/50 • Number of events 54
|
|
Blood and lymphatic system disorders
Hematuria (in the absence of vaginal bleeding)
|
4.0%
2/50 • Number of events 2
|
|
Blood and lymphatic system disorders
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia
|
2.0%
1/50 • Number of events 1
|
|
Blood and lymphatic system disorders
Vaginal bleeding
|
4.0%
2/50 • Number of events 2
|
|
Hepatobiliary disorders
Alkaline phosphatase
|
26.0%
13/50 • Number of events 22
|
|
Hepatobiliary disorders
Bilirubin
|
8.0%
4/50 • Number of events 4
|
|
Hepatobiliary disorders
Hypoalbuminemia
|
50.0%
25/50 • Number of events 55
|
|
Hepatobiliary disorders
SGOT (AST) (serum glutamic oxaloacetic transaminase)
|
52.0%
26/50 • Number of events 58
|
|
Hepatobiliary disorders
SGPT (ALT) (serum glutamic pyruvic transaminase)
|
46.0%
23/50 • Number of events 52
|
|
Infections and infestations
Catheter-related infection
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Febrile neutropenia
|
6.0%
3/50 • Number of events 3
|
|
Infections and infestations
Infection
|
4.0%
2/50 • Number of events 2
|
|
Infections and infestations
Infection without neutropenia
|
32.0%
16/50 • Number of events 29
|
|
Infections and infestations
Infection/Febrile Neutropenia-Other (Specify, vag. yeast infection)
|
6.0%
3/50 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
2.0%
1/50 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.0%
1/50 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
2.0%
1/50 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
2.0%
1/50 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypernatremia
|
2.0%
1/50 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
10.0%
5/50 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalemia
|
46.0%
23/50 • Number of events 44
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
18.0%
9/50 • Number of events 15
|
|
Metabolism and nutrition disorders
Hyponatremia
|
34.0%
17/50 • Number of events 22
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness (not due to neuropathy)
|
18.0%
9/50 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal-Other (Specify, fracture of L. fibula)
|
2.0%
1/50 • Number of events 1
|
|
Nervous system disorders
Ataxia (incoordination)
|
8.0%
4/50 • Number of events 4
|
|
Nervous system disorders
Confusion
|
10.0%
5/50 • Number of events 5
|
|
Nervous system disorders
Dizziness/lightheadedness
|
14.0%
7/50 • Number of events 9
|
|
Nervous system disorders
Insomnia
|
12.0%
6/50 • Number of events 8
|
|
Nervous system disorders
Mood alteration-anxiety, agitation
|
4.0%
2/50 • Number of events 2
|
|
Nervous system disorders
Mood alteration-depression
|
6.0%
3/50 • Number of events 5
|
|
Nervous system disorders
Neurology-Other (Specify, largyngitis, voice hoarseness; neurology: Tinnitus L>R )
|
4.0%
2/50 • Number of events 2
|
|
Nervous system disorders
Neuropathy - motor
|
4.0%
2/50 • Number of events 2
|
|
Nervous system disorders
Neuropathy-sensory
|
58.0%
29/50 • Number of events 48
|
|
Eye disorders
Cataract
|
2.0%
1/50 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
2.0%
1/50 • Number of events 1
|
|
Eye disorders
Dry eye
|
2.0%
1/50 • Number of events 1
|
|
Eye disorders
Tearing (watery eyes)
|
4.0%
2/50 • Number of events 2
|
|
Eye disorders
Vision-blurred vision
|
8.0%
4/50 • Number of events 4
|
|
Eye disorders
Vision-flashing lights/floaters
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain or cramping
|
38.0%
19/50 • Number of events 29
|
|
Musculoskeletal and connective tissue disorders
Arthralgia (joint pain)
|
66.0%
33/50 • Number of events 93
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.0%
2/50 • Number of events 3
|
|
General disorders
Chest pain (non-cardiac and non-pleuritic)
|
4.0%
2/50 • Number of events 2
|
|
Ear and labyrinth disorders
Earache (otalgia)
|
2.0%
1/50 • Number of events 1
|
|
Nervous system disorders
Headache
|
18.0%
9/50 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Myalgia (muscle pain)
|
22.0%
11/50 • Number of events 18
|
|
General disorders
Pain-Other (Specify, Back Pain; Neck; Flank R; Pain in right rib )
|
8.0%
4/50 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Rectal or perirectal pain (proctalgia)
|
2.0%
1/50 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.0%
3/50 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
24.0%
12/50 • Number of events 14
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.0%
1/50 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
2.0%
1/50 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Voice changes/stridor/larynx (e.g., hoarseness, loss of voice, laryngitis)
|
6.0%
3/50 • Number of events 4
|
|
Renal and urinary disorders
Proteinuria
|
2.0%
1/50 • Number of events 1
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
6.0%
3/50 • Number of events 4
|
|
Renal and urinary disorders
Urinary retention
|
10.0%
5/50 • Number of events 5
|
|
Reproductive system and breast disorders
Vaginitis (not due to infection)
|
2.0%
1/50 • Number of events 1
|
|
Reproductive system and breast disorders
Sexual/Reproductive Function-Other (Specify, Amenorrhea)
|
2.0%
1/50 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other (Specify, Head Rash; pain: port problems, pain, redness )
|
4.0%
2/50 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal-Other (Specify, dental extraction; early satiety; bloating)
|
6.0%
3/50 • Number of events 3
|
Additional Information
Antonio Fojo, M.D.
National Cancer Institute, National Institutes of Health
Phone: 301-496-2631
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place