Prostate Cancer
Conditions
Keywords
Prostate Cancer, Metastatic Prostate Cancer, Prostate adenocarcinoma, Androgen-Dependent Prostate Cancer, Cabozantinib, XL 184, Androgen Ablation
Brief summary
The goal of this clinical research study is learn if adding cabozantinib (also known as XL184) to hormonal therapy can help to control prostate cancer. The safety of this drug will also be studied. Cabozantinib is designed to block certain proteins in your blood that cause cancer cells to grow. This may cause cancer cells to die.
Detailed description
Study Drug Administration: If you are found to be eligible to take part in this study, you will take 1 capsule of cabozantinib by mouth 1 time every day while you are on study. You should not eat or drink anything other than water for 2 hours before and 1 hour after taking the study drug. You should take the capsule with at least 1 cup (8 ounces) of water. You will also be given separate directions about how to take the study drug. You will also receive hormone therapy. The hormone drug you receive will be standard of care hormone therapy. The study doctor will decide what hormone therapy you will receive and will explain when and how you should take the hormone therapy, as well as its risks. You will be given a drug diary where you will record when you take cabozantinib. You should return this diary to the study staff when you come into the clinic. Study Visits: At every visit, you will be asked about any side effects you may have had and any other drugs you may be taking. If you are receiving Coumadin, every week for the first 3 weeks, you will have blood drawn (about 1 teaspoon) to test your blood clotting function. Every 3 weeks for the first 12 weeks of the study, and then every 6 weeks after that: * You will have a physical exam. * Blood (about 3-4 teaspoons) will be drawn for routine tests. Every 3 weeks for the first 12 weeks of the study, and then every 12 weeks after that, blood (about 1 teaspoon) will be drawn to check your thyroid and pancreatic function. The frequency of the testing may change if the study doctor thinks it is needed. Every 6 weeks, you will have the following tests performed: * Blood (about 2-3 teaspoons) will be drawn to measure your PSA levels and for biomarker testing. * Urine will be collected for routine tests. * You may have these test performed near your home if the study doctor thinks you are tolerating the treatment. Every 12 weeks, you will have a bone scan and CT scans of the chest, abdomen, and pelvis to check the status of the disease. Length of Study: You may continue receiving the study drug for as long as the study doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse, if you have intolerable side effects, or if your study doctor thinks it is in your best interest to stop. Long-Term Follow-Up: You will be contacted every 6 months after you stop taking the study drug to check on how you are feeling and the status of the disease. This will consist of a phone call, e-mail, or medical record review. If you are called, each call should last about 5 minutes. This is an investigational study. Cabozantinib is FDA approved to treat patients with certain types of thyroid cancer. Its use in this study is investigational. Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGCabozantinib
Starting dose of 60 mg by mouth every day of a 21 day cycle.
DRUGAndrogen Ablation Therapy
Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.
Sponsors
Exelixis
High Impact Clinical Research Support Program
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
1. Histologic proof of prostate adenocarcinoma 2. Newly diagnosed Androgen-Dependent Prostate Cancer. Patients already on ADT are eligible as long as the time from initiation of LHRH analog or antagonist is not greater than 3 months. 3. Metastatic disease on bone scan and/or involvement of soft tissues (lymph nodes and/or viscera) by CT scan, PET/CT, or MRI 4. PSA \> 1 ng/ml, unless anaplastic features are present (according to eligibility 10) 5. Life expectancy from a co-morbid illness \> 3 years 6. Eastern Cooperative Oncology Group (ECOG) performance status \</= 2 7. Patients must have adequate organ function as defined by: Absolute Neutrophil Count (ANC) \>/= 1,500/ul (unless due to bone marrow infiltration by tumor in which case ANC \>/=500/ml are allowed) Hemoglobin (Hgb) \>/= 9 gm/dL (unless due to bone marrow infiltration by tumor in which case Hgb\>8 gm/dL); Total bilirubin \</= 1.5times the upper limit of normal (ULN). For patients with known Gilbert's disease, total bilirubin should be \</= 3mg/dL; platelet count \>/= 100,000/mm\^3 (unless due to bone marrow infiltration by tumor in which case \>/=50,000/ml are allowed); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \</= 3.0 x ULN if no liver involvement, or \</= 5 x ULN with liver involvement; Lipase \< 2 x the upper limit of normal; Urine protein/creatinine ratio (UPCR) \</= 1; Serum phosphorus \>/= lower limits of normal (LLN); estimated creatinine clearance of \>/=40 ml/min. 8. Prior ADT is allowed if it was an adjunct to definite local therapy, was given for \</=1 year and was completed at least 12 months before initiating therapy for metastatic disease. 9. Prior therapy with other tyrosine kinase inhibitors (TKI) inhibitors or any other type of investigational agent is allowed if it was an adjunct to definitive local therapy, was given for \</=6 months, and was completed at least 12 months before initiating therapy for metastatic disease. 10. Patients with anaplastic features are eligible for this trial as defined by at least one of the following: a) Any of the following metastatic presentations: exclusive visceral metastases, radiographically predominant lytic bone metastases identified by plain X-ray or CT scan, bulky (\>5 cm in longest dimension) lymphadenopathy or high-grade (gleason \>8) tumor mass in the prostate/pelvis.; b) Low PSA (\</= 10 ng/ml) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (\>/=20) bone metastases.; c) Elevated serum LDH (\>/= 2 x ULN) or elevated serum CEA (\>/= 2 x ULN) in the absence of other etiologies.; d) Short interval (\</= 180 days) to castrate-resistant progression following initiation of hormonal therapy. 11. Sexually active fertile subjects, and their partners, must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study drug(s).
Exclusion criteria
1. Biological agents (antibodies, immune modulators, cytokines, or vaccines) or radionuclide treatment within 6 weeks of the first dose of study treatment. 2. Radiation therapy within 2 weeks prior to initiation of study treatment. 3. Symptomatic or uncontrolled brain metastasis or epidural disease requiring current treatment including steroids and anti-convulsant. 4. The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, or superficial bladder cancer. 5. The subject has uncontrolled or significant intercurrent illness including, but not limited to, the following conditions: Chronically uncontrolled hypertension, defined conventionally as consistent and repeated systolic pressures above 140 mmHg or diastolic pressures above 90 mmHg despite anti-hypertensive therapy. This may be better established with home BP readings than with clinic visit results. There is no criterion related to a specific BP result required for eligibility, nor are acute BP elevations that are related to iatrogenic causes, acute pain, or other transient reversible causes considered to be an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | 31.2 months | Progression defined by any of the following: (a) radiographic progression (using RECIST 1.1 for visceral disease and PCWG2 for Bone Scans), (b) receive additional anti-cancer therapy, or (c) clinical progression resulting in stopping the treatment. |
| Serious Adverse Events and Other (Not Including Serious) Adverse Events | Start of treatment up to 30 days after study drug, up to 80 months | Number of instances of Serious Adverse Events and Other (Not Including Serious) Adverse Events. Adverse events were monitored for 30 days beyond the last day of treatment. These adverse events are documented. The adverse events are reported as Serious Adverse Events and Adverse Events. Serious Adverse Events are defined as adverse events in which the participant dies, is hospitalized, is disabled, or is exposed to the medicine while pregnant resulting in and birth defect. Adverse events evaluated for all treated participants using the NCI CTCAE version 4.3. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled from January 2014 - January 2016 at MD Anderson Cancer Center
Participants by arm
| Arm | Count |
|---|---|
| Cabozantinib + Androgen Ablation Therapy Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.
Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.
Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor. | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | 2nd primary tumor | 2 |
| Overall Study | Adverse Event | 9 |
| Overall Study | Automobile accident | 1 |
| Overall Study | Lack of Efficacy | 37 |
| Overall Study | Maximum benefit | 4 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Cabozantinib + Androgen Ablation Therapy |
|---|---|
| Age, Continuous | 62 years |
| Bone Metastases Bone Metastases | 58 Participants |
| Bone Metastases Bone Only | 27 Participants |
| Bone Specific Alkaline Phosphatase Level | 61 µg/L |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 45 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 17 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Gleason Score Gleason 6-7 | 10 Participants |
| Gleason Score Gleason 7 + 5 | 2 Participants |
| Gleason Score Gleason 8-10 | 45 Participants |
| Gleason Score Unknown Gleason Score | 5 Participants |
| Prior Treatment of Primary Tumor No Prior Treatment | 46 Participants |
| Prior Treatment of Primary Tumor Yes Prior Treatment | 16 Participants |
| Prostate Specific Antigen (PSA) Levels | 64.7 ng/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 4 Participants |
| Race (NIH/OMB) White | 57 Participants |
| Region of Enrollment United States | 62 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 62 Participants |
| Soft-Tissue Metastases Liver | 2 Participants |
| Soft-Tissue Metastases Lung | 6 Participants |
| Soft-Tissue Metastases Lymph Nodes | 33 Participants |
| Soft-Tissue Metastases None | 29 Participants |
| Visceral Metastases | 8 Participants |
| Volume of Metastases High | 54 Participants |
| Volume of Metastases Low | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 24 / 62 |
| other Total, other adverse events | 62 / 62 |
| serious Total, serious adverse events | 3 / 62 |
Outcome results
Primary
Progression Free Survival
Progression defined by any of the following: (a) radiographic progression (using RECIST 1.1 for visceral disease and PCWG2 for Bone Scans), (b) receive additional anti-cancer therapy, or (c) clinical progression resulting in stopping the treatment.
Time frame: 31.2 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cabozantinib + Androgen Ablation Therapy | Progression Free Survival | 16.1 months |
Primary
Serious Adverse Events and Other (Not Including Serious) Adverse Events
Number of instances of Serious Adverse Events and Other (Not Including Serious) Adverse Events. Adverse events were monitored for 30 days beyond the last day of treatment. These adverse events are documented. The adverse events are reported as Serious Adverse Events and Adverse Events. Serious Adverse Events are defined as adverse events in which the participant dies, is hospitalized, is disabled, or is exposed to the medicine while pregnant resulting in and birth defect. Adverse events evaluated for all treated participants using the NCI CTCAE version 4.3.
Time frame: Start of treatment up to 30 days after study drug, up to 80 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cabozantinib + Androgen Ablation Therapy | Serious Adverse Events and Other (Not Including Serious) Adverse Events | Other (Not Including Serious) Adverse Events | 2105 adverse events |
| Cabozantinib + Androgen Ablation Therapy | Serious Adverse Events and Other (Not Including Serious) Adverse Events | Serious Adverse Events | 3 adverse events |