Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
Exelixis
High Impact Clinical Research Support Program (HI-CRSP)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01630590
First received: June 26, 2012
Last updated: July 9, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: Cabozantinib
Drug: Androgen Ablation Therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Observational Study of XL-184 Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Castrate-resistant progression defined by any of the following: (a) radiographic progression (using RECIST 1.1 for visceral disease and PCWG2 for Bone Scans), (b) receipt of additional anti-cancer therapy, or (c) clinical progression warranting discontinuation from the study as judged by the treating physician.


Estimated Enrollment: 60
Study Start Date: January 2014
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Cabozantinib
Starting dose of 60 mg by mouth every day of a 21 day cycle.
Other Name: XL 184
Drug: 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.

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.

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 6 weeks, this blood will also be used to check your thyroid function and measure your PSA.
  • Urine will be collected for routine tests (every 6 weeks).

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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 1 month.
  3. Patients must have "high-volume" disease as evidenced by 3 or more bone lesions or involvement of viscera
  4. Metastatic disease on bone scan and/or involvement of soft tissues (lymph nodes and/or viscera) by computed tomography (CT) scan and/or magnetic resonance imaging (MRI)
  5. PSA > 1 ng/ml
  6. Life expectancy from a co-morbid illness > 3 years
  7. Eastern Cooperative Oncology Group (ECOG) performance status </= 2
  8. Patients must have adequate organ function as defined by: Absolute Neutrophil Count (ANC) >/= 1,500/ul (without colony stimulating factor support); Hemoglobin (Hgb) >/= 9 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; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 3.0 x ULN if no liver involvement, or </= 5 x ULN with liver involvement; Lipase < 1.5 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.
  9. Prior ADT is allowed if it was an adjunct to definite local therapy, was given for </= 6 months, and was completed at least 12 months before initiating therapy for metastatic diseases
  10. 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.
  11. 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.
  12. 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 prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test results at screening >/= 1.3 x the laboratory ULN.
  6. The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or Factor Xa (FXa) inhibitors, and antiplatelet agents (eg, clopidogrel). Low dose aspirin (</= 81 mg/day), low-dose warfarin (</= 1 mg/day), and prophylactic Low Molecular Weight Heparin (LMWH) are permitted.
  7. The subject has uncontrolled or significant intercurrent illness including, but not limited to, the following conditions: Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm mercury (Hg) systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (including transient ischemic attack [TIA], or other ischemic event) within 6 months of study treatment, myocardial infarction within 6 months of study treatment, history of thromboembolic event requiring therapeutic anticoagulation within 6 months of study treatment or main portal vein or vena cava thrombosis or occlusion.;Gastrointestinal (GI) disorders particularly those associated with a high risk of perforation or fistula formation including: Any of the following at the time of screening;
  8. Continued from # 7) a) intra-abdominal tumor/metastases invading GI mucosa; b) active peptic ulcer disease; c) inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis;Any of the following within 6 months before the first dose of study treatment: a) history of abdominal fistula; b) gastrointestinal perforation; c) bowel obstruction or gastric outlet obstruction; d) intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 6 months ago.; GI surgery (particularly when associated with delayed or incomplete healing) within 28 days. Note: Complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more that 28 days ago.
  9. Continued from # 8) ;Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus.
  10. The subject is unable to swallow capsules tablets
  11. The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation.
  12. Oral corticosteroids >/= 7.5mg/day prednisone (or prednisone equivalents).
  13. Prior treatment with cabozantinib.
  14. The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) >500 ms within 28 days before randomization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01630590

Contacts
Contact: Paul Corn, MD, PHD 713-792-2830

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Exelixis
High Impact Clinical Research Support Program (HI-CRSP)
Investigators
Principal Investigator: Paul Corn, MD, PHD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01630590     History of Changes
Other Study ID Numbers: 2012-0252, NCI-2014-00934
Study First Received: June 26, 2012
Last Updated: July 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Prostate Cancer
Metastatic Prostate Cancer
Prostate adenocarcinoma
Androgen-Dependent Prostate Cancer
Cabozantinib
XL 184
Androgen Ablation

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014