Tivozanib + Enzalutamide in Adv Prostate Cancer

NCT01885949 | Terminated Phase 2 Results DMC

• 1 other identifier: 13-073
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational combination of drugs to learn whether they work in treating a specific cancer. "Investigational" means that the combination of drugs is still being studied and that research doctors are trying to find out more about it, such as the safest dose to use and the side effects they may cause. It also means that the FDA has not yet approved the combination. The two drugs being tested in this study are tivozanib and enzalutamide. Enzalutamide has been approved by the FDA for treatment of prostate cancer. On the other hand, tivozanib is still investigational, and has not been tested in a combination with enzalutamide before. Enzalutamide is an androgen receptor antagonist (it blocks the activity of the male sex hormones). Prostate cancers are initially dependent on the male hormone testosterone for growth. Hormonal therapies that lower testosterone or block the ability of testosterone to act at the level of the prostate cancer are currently among the most effective treatments for prostate cancers taht have spread to other body organs (metastasized). The effectiveness of hormonal treatments, however, is not permanent, and over time many prostate cancers progress in spite of these treatments. Enzalutamide is a drug that has been proven to help delay the progression of advanced prostate cancer on average for about 8 months. Tivozanib is an anti-angiogenesis medicine that fights different types of cancer by blocking the blood supply to the tumor, so that the tumor does not receive the nutrients it needs to grow. The main goal of this study is to determine whether the combination of tivozanib and enzalutamide is more effective in delaying the progression of disease than when enzalutamide is given alone. This study will also determine whether treatment with the combination of the tivozanib and enzalutamide will have more side effects then treatment with enzalutamide alone.

Conditions

Prostate Cancer

Keywords

Metastatic

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  The primary objective of this study will be to demonstrate an improvement in progression free survival in men with metastatic castration resistant prostate cancer (mCRPC) treated with tivozanib and enzalutamide.

  2 years

Secondary Outcomes (4)

• Safety and Tolerability

  2 years

• Overall Survival

  2 years

• PSA Response Rate

  2 years

• Time to PSA Progression

  2 years

Study Arms (1)

Experimental Treatment Arm

EXPERIMENTAL

Tivozanib, taken daily for 21 days followed by a 7 day break Enzalutamide taken daily for 28 days

Drug: Tivozanib; Drug: Enzalutamide

Interventions

Tivozanib DRUG

Oral

Also known as: AV-951

Experimental Treatment Arm

Enzalutamide DRUG

oral

Also known as: MDV-3100

Experimental Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Adenocarcinoma of the prostate that is metastatic or unresectable and for which standard curative options do not exist
• Radiographic evidence of metastatic prostate cancer
• Progressive disease despite ongoing androgen deprivation therapy (ADT), defined as castration resistant prostate cancer (CRPC)
• Other than ongoing prior treatment with other hormonal agents such as antiandrogens or ketoconazole must have been stopped at least two weeks prior to enrollment
• Have received prior docetaxel-based chemotherapy for prostate cancer within the past 12 months. Such chemotherapy must have been stopped at least 3 weeks prior to the first dosing in this study
• Life expectancy of at least 12 weeks
• Must agree to use adequate contraception prior to study entry and for the duration of study participation

You may not qualify if:

• Prior treatment with enzalutamide, TOK-001, or ARN-509
• Participants who have received more than two prior chemotherapy regimens for metastatic CRPC
• Receiving any other investigational anticancer agents
• Known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib or enzalutamide
• Radiotherapy or minor surgical procedure within 2 weeks, or major surgical procedure within 4 weeks prior to administration of first dose of study drug; inadequate recovery from prior surgical procedure
• History of seizure of condition that may predispose to seizure
• Significant cardiovascular disease
• Non-healing wound, bone fracture or skin ulcer
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug
• Serious/active infection or infection requiring parenteral antibiotics
• Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug
• Currently active second primary malignancy, including hematologic malignancies, except for non-melanoma skin cancers, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast
• History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant
• Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that severly affects the absorption of study drugs, major resection of the stomach or small bowel, or gastric bypass procedure

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

tivozanib; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Dror Michaelson
• Organization: MGH Cancer Center

dmichaelson1@mgh.harvard.edu

6177244000

Study Officials

• M. Dror Michaelson, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: June 25, 2013
• Study Start: September 3, 2013
• Primary Completion: May 23, 2024
• Study Completion: May 23, 2024
• Last Updated: February 24, 2026
• Results First Posted: July 16, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)