Trial Outcomes & Findings for Study Combining Imatinib Mesylate (Gleevec) With Sorafenib in Patients With Androgen-independent Prostate Cancer (AIPC) (NCT NCT00424385)
NCT ID: NCT00424385
Last Updated: 2014-07-21
Results Overview
Eligible patients were enrolled in one of 4 cohorts, where each cohort allowed 3 evaluable patients to be on study, patients withdrawn from treatment for reasons other than toxicity were not considered evaluable. If one of the three evaluable patients experienced a dose limiting toxicity (DLT) the cohort was expanded to 6 evaluable patients. Patients will receive both study drugs on escalated dosing schedule until the maximum of 400 mg PO BID is reached for both drugs or toxicity is established. If 2 out of six evaluable patients experience a dose limiting toxicity this would show that the Maximum Tolerated Dose (MTD) was the dose from the prior cohort.
COMPLETED
PHASE1
17 participants
up to 20 weeks
2014-07-21
Participant Flow
17 patients were enrolled from our practice.
Patients enrolled failed previous chemotherapy.
Participant milestones
| Measure |
Imatinib + Sorafenib
Both drugs, Gleevec + Sorafenib are given to all patients on study. There are 4 potential cohorts. Each will enroll 3 evaluable (patients that complete 2 cycles of treatment) patients. If a Dose Limiting Toxicity is demonstrated in a cohort, an additional 3 evaluable patients can be enrolled in that cohort.
Cohort 0 was 400mg Sorafenib every day (QD)and 300mg of Imatinib QD. Cohort 1 was 400mg Sorafenib two times a day and 300mg QD Imatinib.
|
|---|---|
|
Cohort 0
STARTED
|
12
|
|
Cohort 0
COMPLETED
|
6
|
|
Cohort 0
NOT COMPLETED
|
6
|
|
Cohort 1
STARTED
|
5
|
|
Cohort 1
COMPLETED
|
4
|
|
Cohort 1
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Imatinib + Sorafenib
Both drugs, Gleevec + Sorafenib are given to all patients on study. There are 4 potential cohorts. Each will enroll 3 evaluable (patients that complete 2 cycles of treatment) patients. If a Dose Limiting Toxicity is demonstrated in a cohort, an additional 3 evaluable patients can be enrolled in that cohort.
Cohort 0 was 400mg Sorafenib every day (QD)and 300mg of Imatinib QD. Cohort 1 was 400mg Sorafenib two times a day and 300mg QD Imatinib.
|
|---|---|
|
Cohort 0
Withdrawal by Subject
|
5
|
|
Cohort 0
Physician Decision
|
1
|
|
Cohort 1
Withdrawal by Subject
|
1
|
Baseline Characteristics
Study Combining Imatinib Mesylate (Gleevec) With Sorafenib in Patients With Androgen-independent Prostate Cancer (AIPC)
Baseline characteristics by cohort
| Measure |
Arm 1
n=17 Participants
Only 1 arm for the study - this arm gets both drugs, gleevec and sorafenib
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to 20 weeksPopulation: Cohort 0: 6 evaluable patients were enrolled. Patients who withdrew for reasons other than toxicity were not considered evaluable for MTD. 1 out of 6 patients had a DLT, therefore Cohort 1 was started. Cohort 1: 2 DLTs were demonstrated from 5 evaluable patients. By definition the Maximum tolerated dose was the dosing schedule used in cohort 0.
Eligible patients were enrolled in one of 4 cohorts, where each cohort allowed 3 evaluable patients to be on study, patients withdrawn from treatment for reasons other than toxicity were not considered evaluable. If one of the three evaluable patients experienced a dose limiting toxicity (DLT) the cohort was expanded to 6 evaluable patients. Patients will receive both study drugs on escalated dosing schedule until the maximum of 400 mg PO BID is reached for both drugs or toxicity is established. If 2 out of six evaluable patients experience a dose limiting toxicity this would show that the Maximum Tolerated Dose (MTD) was the dose from the prior cohort.
Outcome measures
| Measure |
Imatinib + Sorafenib Cohort 0
n=6 Participants
300mg every day (QD)Imatinib + 400mg every day (QD) Sorafenib, by mouth
|
Imatinib + Sorafenib Cohort 1
n=5 Participants
300mg every day (QD) Imatinib + 400mg twice daily (BID)Sorafenib, by mouth
|
|---|---|---|
|
Number of Patients Experiencing Dose Limiting Toxicities (DLT's)
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: up to 20 weeksPopulation: There were 17 patients enrolled. 10 were evaluable for assessment of overall clinical benefit. 7 were not evaluable due to having received \<1 cycle of drug.
Overall Clinical Benefit was measured as the sum of complete response (CR), partial response (PR), and stable disease (SD).
Outcome measures
| Measure |
Imatinib + Sorafenib Cohort 0
n=10 Participants
300mg every day (QD)Imatinib + 400mg every day (QD) Sorafenib, by mouth
|
Imatinib + Sorafenib Cohort 1
300mg every day (QD) Imatinib + 400mg twice daily (BID)Sorafenib, by mouth
|
|---|---|---|
|
Overall Clinical Benefit
|
20 percentage of evaluable participants
|
—
|
SECONDARY outcome
Timeframe: up to 5 cycles, an average of 20 weeks, from the day of first treatment until the date of the last dose of study drugMedium TTP is 2 months (range 1-5). 10 patients were evaluable for disease progression for these patients occurred between 1-5 months after starting the study. The TTP was calculated per protocol. For radiographic assessment Response Evaluation Criteria in Solid Tumors (RECIST) was used. Complete response = disappearance of all lesions. Partial response (PR)=30% or greater decrease in sum of longest diameter of measureable lesions SD. Lesions have no sufficient decrease for progressive disease and no sufficient increase to meet Progressive Disease (PD). PD more than 20% increase in sum of longest diameter of measurable lesions or 2 or more new bone mets. prostate-specific antigen (PSA) assessment for patients with measurable disease, PSA progression in the absence of measurable disease progression will not be considered progressive disease.
Outcome measures
| Measure |
Imatinib + Sorafenib Cohort 0
n=10 Participants
300mg every day (QD)Imatinib + 400mg every day (QD) Sorafenib, by mouth
|
Imatinib + Sorafenib Cohort 1
300mg every day (QD) Imatinib + 400mg twice daily (BID)Sorafenib, by mouth
|
|---|---|---|
|
Time to Disease Progression (TTP)
|
2 months
Interval 1.0 to 5.0
|
—
|
Adverse Events
Arm 1
Serious adverse events
| Measure |
Arm 1
n=17 participants at risk
Only 1 arm for the study - this arm gets both drugs, gleevec and sorafenib
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Broken C2 verebrae
|
5.9%
1/17
|
|
General disorders
Pain
|
5.9%
1/17
|
|
Gastrointestinal disorders
Nausea
|
11.8%
2/17
|
|
Gastrointestinal disorders
Vomiting
|
11.8%
2/17
|
|
Renal and urinary disorders
Urinary Tract Infection
|
5.9%
1/17
|
|
Cardiac disorders
Chest pain
|
5.9%
1/17
|
|
Cardiac disorders
Syncopal episode
|
5.9%
1/17
|
|
Gastrointestinal disorders
Dehydration
|
11.8%
2/17
|
|
Gastrointestinal disorders
Diarrhea
|
11.8%
2/17
|
|
General disorders
Weakness
|
5.9%
1/17
|
|
Cardiac disorders
Atrial Fibrillation
|
5.9%
1/17
|
|
General disorders
Syndrome of Inappropriate Antiduretic Hormone
|
5.9%
1/17
|
Other adverse events
| Measure |
Arm 1
n=17 participants at risk
Only 1 arm for the study - this arm gets both drugs, gleevec and sorafenib
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
58.8%
10/17
|
|
Gastrointestinal disorders
Appetite decreased
|
35.3%
6/17
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.8%
2/17
|
|
Gastrointestinal disorders
Albumin Low
|
47.1%
8/17
|
|
General disorders
Bruises easily
|
5.9%
1/17
|
|
General disorders
Alopecia
|
17.6%
3/17
|
|
Psychiatric disorders
Anxiety
|
5.9%
1/17
|
|
Cardiac disorders
Atrial Fibrillation
|
5.9%
1/17
|
|
Hepatobiliary disorders
Alkaline Phosphatase
|
29.4%
5/17
|
|
Hepatobiliary disorders
AST increased
|
23.5%
4/17
|
|
Renal and urinary disorders
Bilirubin increased
|
11.8%
2/17
|
|
Cardiac disorders
Chest Pain
|
5.9%
1/17
|
|
General disorders
Chloride Low
|
17.6%
3/17
|
|
General disorders
Chills
|
5.9%
1/17
|
|
Gastrointestinal disorders
Constipation
|
11.8%
2/17
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17
|
|
Renal and urinary disorders
Creatinine Increased
|
23.5%
4/17
|
|
Hepatobiliary disorders
Alt Increased
|
5.9%
1/17
|
|
Eye disorders
Eyes tearing
|
11.8%
2/17
|
|
General disorders
Edema lower extremity
|
11.8%
2/17
|
|
General disorders
Edema periorbital
|
5.9%
1/17
|
|
General disorders
Edema ankle
|
5.9%
1/17
|
|
Ear and labyrinth disorders
Ear sore
|
5.9%
1/17
|
|
General disorders
Fatigue
|
41.2%
7/17
|
|
Musculoskeletal and connective tissue disorders
Foot pain
|
5.9%
1/17
|
|
Infections and infestations
Fever
|
11.8%
2/17
|
|
General disorders
Fall
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Desquamation
|
35.3%
6/17
|
|
Gastrointestinal disorders
Diarrhea
|
47.1%
8/17
|
|
Gastrointestinal disorders
Dehydration
|
23.5%
4/17
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea on Excertion
|
17.6%
3/17
|
|
Psychiatric disorders
Depression
|
5.9%
1/17
|
|
Cardiac disorders
Hypotension
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Hand Foot Syndrome
|
17.6%
3/17
|
|
Gastrointestinal disorders
Hypokalemia
|
11.8%
2/17
|
|
Gastrointestinal disorders
Hypercalcemia
|
5.9%
1/17
|
|
Renal and urinary disorders
Hematuria
|
5.9%
1/17
|
|
Gastrointestinal disorders
Hypocalcemia
|
58.8%
10/17
|
|
Gastrointestinal disorders
Hyperkalemia
|
23.5%
4/17
|
|
Gastrointestinal disorders
Hyponatremia
|
23.5%
4/17
|
|
General disorders
Hot Flashes
|
5.9%
1/17
|
|
Endocrine disorders
Hyperglycemia
|
17.6%
3/17
|
|
General disorders
Insomnia
|
11.8%
2/17
|
|
Skin and subcutaneous tissue disorders
Itching
|
17.6%
3/17
|
|
Infections and infestations
Infection
|
11.8%
2/17
|
|
Blood and lymphatic system disorders
Leukopenia
|
17.6%
3/17
|
|
Blood and lymphatic system disorders
Lymphopenia
|
35.3%
6/17
|
|
Reproductive system and breast disorders
Libido decreased
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Muscle Pain
|
11.8%
2/17
|
|
Gastrointestinal disorders
Mouth Dry
|
11.8%
2/17
|
|
Gastrointestinal disorders
Mucositis
|
5.9%
1/17
|
|
Gastrointestinal disorders
Magnesium decreased
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
5.9%
1/17
|
|
Musculoskeletal and connective tissue disorders
Neuropathy
|
5.9%
1/17
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Nail Changes
|
11.8%
2/17
|
|
Gastrointestinal disorders
Nausea
|
35.3%
6/17
|
|
Gastrointestinal disorders
Oral candidiasis
|
5.9%
1/17
|
|
Blood and lymphatic system disorders
Pancytopenia
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Palmar erythema
|
5.9%
1/17
|
|
General disorders
Pain
|
35.3%
6/17
|
|
Gastrointestinal disorders
Phosphorus High
|
5.9%
1/17
|
|
Skin and subcutaneous tissue disorders
Photo Sensitivity
|
11.8%
2/17
|
|
Gastrointestinal disorders
Total Protein Decreased
|
23.5%
4/17
|
Additional Information
Sigrun Hallmeyer, MD Director of Research; Chadi Nabhan, MD FACP (PI)
Oncology Specialists, SC
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place