Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer
Conditions
Brief summary
This phase I/II trial studies the side effects and best dose of pasireotide and to see how well it works when given together with docetaxel and prednisone in treating patients with metastatic hormone-resistant prostate cancer. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pasireotide may inhibit the secretion of hormones. Giving pasireotide together with docetaxel and prednisone may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) level of SOM 230 (pasireotide) in combination with docetaxel and prednisone. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of the combination in metastatic castration-resistant prostate cancer (CRPC). II. To evaluate preliminary efficacy of the combination of SOM 230 and docetaxel and prednisone as defined by response rates (measurable and prostate-specific antigen \[PSA\]), time to progression (TTP) and overall survival (OS). III. To evaluate the pharmacokinetics (PK) of the combination. IV. To assess the pharmacodynamic (PD) effects of the combination as seen by baseline levels of and changes in insulin-like growth factor (IGF)-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), and to associate them with TTP and OS. V. To assess the pretherapy circulating tumor cell (CTC) counts and change in CTC after therapy, and to associate them with TTP and OS. OUTLINE: This is a phase I dose-escalation study of pasireotide followed by a phase II study. Patients receive pasireotide intramuscularly (IM) on day 1, docetaxel intravenously (IV) over 1 hour, and prednisone orally (PO) twice daily (BID) continuously. Courses with docetaxel repeat every 21 days and courses with pasireotide repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 28 days and then every 3 months thereafter.
Interventions
DRUGdocetaxel
Given IV
DRUGpasireotide
Given IM
DRUGprednisone
Given PO
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed prostate adenocarcinoma with metastasis, and objective progression or rising PSA despite androgen deprivation therapy and antiandrogen withdrawal when applicable; patients with rising PSA must demonstrate a rising trend with 2 successive elevations at a minimum interval of 1 week; a minimum PSA of 5 ng/ml or new areas of bony metastases on bone scan are required for patients with no measurable disease; no minimum PSA requirement for patients with measurable disease * Patient must not have received any prior chemotherapy for metastatic disease; all patients must be documented to be castrate with a testosterone level \< 0.5 ng/ml; luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued, if required to maintain castrate levels of testosterone; patients must be off antiandrogens for a minimum of 4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide * Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy) * Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 * Life expectancy 12 weeks or more * Absolute neutrophil (ANC) \>= 1.5 x 10\^9/L * Platelets \>= 100 x 10\^9/L * Hemoglobin (Hgb) \> 9 g/dL * Serum bilirubin =\< 2 x upper limit of normal (ULN) * Serum transaminases activity =\< 3 x ULN, with the exception of serum transaminases (\< 5 x ULN) if the patient has liver metastases * Serum creatinine =\< 1.5 x ULN * Fasting serum cholesterol =\< 300 mg/dL OR =\< 7.75 mmol/L AND fasting triglycerides =\< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication * Patients must be advised of the importance of using effective birth control measures during the course of the study * Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information
Exclusion criteria
* Prior treatment with any cytotoxic chemotherapy, radiation, immunotherapy, or any investigational drug within the preceding 4 weeks * Patients who have undergone major surgery within 4 weeks prior to study enrollment * Chronic treatment with immunosuppressive agents except steroids * Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry * Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases * Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years * Patients with uncontrolled diabetes mellitus, which is defined as a hemoglobin A1C \> 8% on therapy or \> 7% without therapy, or a fasting plasma glucose \> 1.5 ULN; Note: at the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted * Patients with symptomatic cholelithiasis * Patients who have congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), unstable angina, sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment * QT-related
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Up to day 57 | To identify the maximum tolerated dose (MTD) of pasireotide, The occurrence rate of binary endpoints (eg, specific types of toxicity at a certain dose level and severity grade, response, etc) will be described by point estimates and exact 90% confidence intervals (CIs) for proportions using Wilson's method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel | Every 12 weeks for the first 36 weeks and then every 16 weeks thereafter up to 100 weeks | Percentage of participants responding to treatment by measurements of tumor using Response Evaluation Criteria In Solid Tumors (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, before and after treatment with the combination of pasireotide in combination with docetaxel |
| Percentage Prostate-specific Antigen (PSA) Change Noted | On days 1, 22, 43 | Percentage change of prostate-specific antigen (PSA) decline or increase noted |
| Time to Progression (TTP) | Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study, up to 2 years | Time from Treatment start date to Progression (TTP) Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | On days 1, 8, 15, 22, 29, 36 43, 50 and 57 | The count of patients who experience a given type and grade of toxicity as assessed via NCI CTCAE version 4.0 |
| Pharmacokinetics (PK) of SOM230 | Predosing/end of infusion/2, 3, 4 ,7, 24 and 48 hours after start of docetaxel; Day 43; predosing for docetaxel and pasireotide/end of infusion/2, 3, 4, 7, 24 hours day 44/48 hours day 45 after start of infusion; days 29, 57, and 85 prior to pasireotide | Pharmacokinetics (PK) of SOM230 measured in the bloodstream (in ng/ml) at days 29, 57, and 85. |
| Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | Baseline and days 22 and 43 | Measurement of levels of IGF-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), the change between time points (day 22 and day 43) from day 1 as measured in percent change. |
| Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy | Baseline and days 22 and 43 | Measurements of CTC counts, the change between time-points (day 22 and day 43) from day 1 as measured in percent change. |
| Overall Survival (OS) | Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study | Time from Treatment start date to date of death or last follow-up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy, Receptor Agonist) Patients receive pasireotide IM on day 1, docetaxel IV over 1 hour, and prednisone PO BID continuously. Courses with docetaxel repeat every 21 days and courses with pasireotide repeat every 28 days in the absence of disease progression or unacceptable toxicity.
docetaxel: Given IV
pasireotide: Given IM
prednisone: Given PO | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy, Receptor Agonist) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 65 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 14 / 18 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
To identify the maximum tolerated dose (MTD) of pasireotide, The occurrence rate of binary endpoints (eg, specific types of toxicity at a certain dose level and severity grade, response, etc) will be described by point estimates and exact 90% confidence intervals (CIs) for proportions using Wilson's method.
Time frame: Up to day 57
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | 60 mg |
Secondary
Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy
Measurement of levels of IGF-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), the change between time points (day 22 and day 43) from day 1 as measured in percent change.
Time frame: Baseline and days 22 and 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | NSE day 1 to day 43 | 8.00 percent change of biomarker from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | IGF-1 day 1 to day 22 | -47.74 percent change of biomarker from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | IGF-1 day 1 to day 43 | -65.64 percent change of biomarker from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | SCA day 1 to day 22 | -25.36 percent change of biomarker from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | SCA day 1 to day 43 | -21.43 percent change of biomarker from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy | NSE day 1 to day 22 | -17.00 percent change of biomarker from day 1 |
Secondary
Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy
Measurements of CTC counts, the change between time-points (day 22 and day 43) from day 1 as measured in percent change.
Time frame: Baseline and days 22 and 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy | CTC from day 1 to day 22 | -5.50 percent change of CTC from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy | CTC from day 1 to day 43 | -29.50 percent change of CTC from day 1 |
Secondary
Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel
Percentage of participants responding to treatment by measurements of tumor using Response Evaluation Criteria In Solid Tumors (RECISTv1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR, before and after treatment with the combination of pasireotide in combination with docetaxel
Time frame: Every 12 weeks for the first 36 weeks and then every 16 weeks thereafter up to 100 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel | 44.4 percentage of participants |
Secondary
Overall Survival (OS)
Time from Treatment start date to date of death or last follow-up.
Time frame: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Overall Survival (OS) | 18.3 months |
Secondary
Percentage Prostate-specific Antigen (PSA) Change Noted
Percentage change of prostate-specific antigen (PSA) decline or increase noted
Time frame: On days 1, 22, 43
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Percentage Prostate-specific Antigen (PSA) Change Noted | from day 1 to day 22 | -18.52 percentage change of PSA from day 1 |
| Treatment (Chemotherapy, Receptor Agonist) | Percentage Prostate-specific Antigen (PSA) Change Noted | from day 1 to day 43 | -31.49 percentage change of PSA from day 1 |
Secondary
Pharmacokinetics (PK) of SOM230
Pharmacokinetics (PK) of SOM230 measured in the bloodstream (in ng/ml) at days 29, 57, and 85.
Time frame: Predosing/end of infusion/2, 3, 4 ,7, 24 and 48 hours after start of docetaxel; Day 43; predosing for docetaxel and pasireotide/end of infusion/2, 3, 4, 7, 24 hours day 44/48 hours day 45 after start of infusion; days 29, 57, and 85 prior to pasireotide
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Pharmacokinetics (PK) of SOM230 | Level at day 29 | 15.4 ng/ml |
| Treatment (Chemotherapy, Receptor Agonist) | Pharmacokinetics (PK) of SOM230 | Level at day 57 | 14.9 ng/ml |
| Treatment (Chemotherapy, Receptor Agonist) | Pharmacokinetics (PK) of SOM230 | Level at day 85 | 14.5 ng/ml |
Secondary
The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0
The count of patients who experience a given type and grade of toxicity as assessed via NCI CTCAE version 4.0
Time frame: On days 1, 8, 15, 22, 29, 36 43, 50 and 57
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Diarrhea grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Tremor grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Wheezing grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Abdominal pain grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Agitation grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Alkaline phosphatase increased grade 3 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Allergic reaction grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Alopecia grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Alopecia grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Anemia grade 1 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Anemia grade 3 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Anorexia grade 1 | 6 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Anorexia grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Arthritis grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Aspartate aminotransferase increased grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Aspartate aminotransferase increased grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Back pain grade 1 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Back pain grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Bladder infection grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Blood and lymphatic system disorders-Other grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Bruising grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Cardiac disorders - Other, specify grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Cataract grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Chills grade 1 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Cholesterol high grade 1 | 5 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Conjunctivitis grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Constipation grade 1 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Cough grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Cough grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Creatinine increased grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dehydration grade 2 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dehydration grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Depression grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Diarrhea grade 1 | 10 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Diarrhea grade 2 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dizziness grade 1 | 8 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dry mouth grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dry skin grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dysgeusia grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dysgeusia grade 2 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Dyspnea grade 1 | 6 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Ear and labyrinth disorders-Other, specify grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Edema limbs grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Edema limbs grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | EKG QT corrected interval prolong grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | EKG QT corrected interval prolong grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | EKG QT corrected interval prolong grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Eye disorders - Other, specify grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Fatigue grade 1 | 6 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Lymphocyte count decreased grade 4 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Fatigue grade 2 | 7 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Fatigue grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Fever grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Flank pain grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Flu like symptoms grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Flushing grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Gastroesophageal reflux disease grade 1 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Gastroesophageal reflux disease grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Gastrointestinal disorders -Other, specify grade 1 | 7 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Generalized muscle weakness grade 1 | 5 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Generalized muscle weakness grade 2 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Headache grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hearing impaired grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Heart failure grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hematuria grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hematuria grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hoarseness grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hot flashes grade 1 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hyperglycemia grade 1 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hyperglycemia grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hyperglycemia grade 3 | 10 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hyperkalemia grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypertension grade 2 | 5 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypertension grade 3 | 5 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypertriglyceridemia grade 1 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypertriglyceridemia grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypoalbuminemia grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypocalcemia grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypocalcemia grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypokalemia grade 2 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypomagnesemia grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypomagnesemia grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hyponatremia grade 3 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypophosphatemia grade 3 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypotension grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Hypothyroidism grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Infusion related reaction grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Infusion site extravasation grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Injection site reaction grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Insomnia grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Localized edema grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Lymphedema grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Lymphocyte count decreased grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Lymphocyte count decreased grade 3 | 7 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Mucositis oral grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Muscle weakness lower limb grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Musculoskeletal and connective tissue dis. grade 1 | 5 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Myalgia grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nail discoloration grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nail discoloration grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nail loss grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nail ridging grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nasal congestion grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nausea grade 1 | 10 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nausea grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Nervous system disorders - Other grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Neutrophil count decreased grade 3 | 10 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Neutrophil count decreased grade 4 | 6 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Otitis externa grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Pain grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Pain in extremity grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Pelvic pain grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Penile infection grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Penile pain grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Peripheral sensory neuropathy grade 1 | 7 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Peripheral sensory neuropathy grade 2 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Platelet count decreased grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Rash acneiform grade 1 | 6 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Rash acneiform grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Rectal pain grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Renal and urinary disorders - Other grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Renal and urinary disorders - Other grade 2 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Respiratory, thoracic and mediastinal dis. grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Serum amylase increased grade 4 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Sinus disorder grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Sinusitis grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Skin and subcutaneous tissue disorders grade 1 | 9 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Skin and subcutaneous tissue disorders grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Skin infection grade 4 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Sore throat grade 1 | 3 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Thromboembolic event grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Toothache grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Upper respiratory infection grade 1 | 2 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Upper respiratory infection grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Upper respiratory infection grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Urinary frequency grade 1 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Urinary tract infection grade 2 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Urinary tract infection grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Urinary tract obstruction grade 2 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Vomiting grade 1 | 4 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Watering eyes grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Weight loss grade 1 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Weight loss grade 2 | 6 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | Weight loss grade 3 | 1 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | White blood cell decreased grade 3 | 11 Participants |
| Treatment (Chemotherapy, Receptor Agonist) | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 | White blood cell decreased grade 4 | 3 Participants |
Secondary
Time to Progression (TTP)
Time from Treatment start date to Progression (TTP) Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study, up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Chemotherapy, Receptor Agonist) | Time to Progression (TTP) | 7.2 months |