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

NCT01630590 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2012-0252NCI-2014-00934
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Metastatic Prostate Cancer; Prostate adenocarcinoma; Androgen-Dependent Prostate Cancer; Cabozantinib; XL 184; Androgen Ablation

Outcome Measures

Primary Outcomes (2)

• 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.

  31.2 months

• 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.

  Start of treatment up to 30 days after study drug, up to 80 months

Study Arms (1)

Cabozantinib + Androgen Ablation Therapy

EXPERIMENTAL

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; Drug: Androgen Ablation Therapy

Interventions

Cabozantinib DRUG

Starting dose of 60 mg by mouth every day of a 21 day cycle.

Also known as: XL 184

Cabozantinib + Androgen Ablation Therapy

Androgen Ablation Therapy DRUG

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.

Cabozantinib + Androgen Ablation Therapy

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic proof of prostate adenocarcinoma
• 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.
• Metastatic disease on bone scan and/or involvement of soft tissues (lymph nodes and/or viscera) by CT scan, PET/CT, or MRI
• PSA \> 1 ng/ml, unless anaplastic features are present (according to eligibility 10)
• Life expectancy from a co-morbid illness \> 3 years
• Eastern Cooperative Oncology Group (ECOG) performance status \</= 2
• 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.
• 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.
• 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.
• 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.
• 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).

You may not qualify if:

• Biological agents (antibodies, immune modulators, cytokines, or vaccines) or radionuclide treatment within 6 weeks of the first dose of study treatment.
• Radiation therapy within 2 weeks prior to initiation of study treatment.
• Symptomatic or uncontrolled brain metastasis or epidural disease requiring current treatment including steroids and anti-convulsant.
• 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.
• Continued from # 5) Other cardiovascular disorders such as symptomatic congestive heart failure (CHF), 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; 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
• Continued from # 6) 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. Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus.
• The subject is unable to swallow capsules tablets
• The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation.
• Oral corticosteroids \>/= 7.5mg/day prednisone (or prednisone equivalents).
• Prior treatment with cabozantinib.
• The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \>500 ms within 28 days before randomization.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Exelixis: collaborator
• High Impact Clinical Research Support Program: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Paul Corn, Chair Ad Interim, Genitourinary Medical Oncology
• Organization: UT MD Anderson Cancer Center

pcorn@mdanderson.org

(713) 563-7208

Study Officials

• Paul Corn, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2012
• First Posted: June 28, 2012
• Study Start: January 8, 2014
• Primary Completion: April 6, 2021
• Study Completion: April 6, 2021
• Last Updated: March 25, 2022
• Results First Posted: March 25, 2022

Record last verified: 2022-03

Locations

US (1)