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Tivozanib + Enzalutamide in Adv Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01885949
Recruitment Status : Active, not recruiting
First Posted : June 25, 2013
Last Update Posted : June 13, 2018
National Comprehensive Cancer Network
Information provided by (Responsible Party):
Dror Michaelson, MD, Massachusetts General Hospital

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Tivozanib Drug: Enzalutamide Phase 2

Detailed Description:

Patients will be treated in treatment cycles of 28 days (4 weeks), during which time they will take tivozanib once a day for 21 days (3 weeks) followed by a one week break from treatment. The other medication, enzalutamide, will be taken every day throughout each cycle.

Patients will be given a Study Drug Administration Diary to keep a brief record of medication administration, and to record any side effects or symptoms.

Patients will be seen in the clinic at the beginning of each cycle (every 4 weeks). During each visit they will have the following procedures: medical history, vital sign measurements, complete physical examination, performance status, routine blood tests, urine sample, prostate specific antigen (PSA) test, assessment of tumor, review of study drug administration diary, and review of current medications.

About four weeks after stopping the study drug patients will be asked to return to the research clinic for a final study visit. The following procedures will be done: medical history, vital sign measurements, brief physical examination, electrocardiogram, review of other medications used since the last visit, routine blood tests, urine sample and a review of any changes in health.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Combination Trial of Tivozanib and Enzalutamide in Men With Advanced Prostate Cancer
Study Start Date : June 2013
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Experimental Treatment Arm
Tivozanib, taken daily for 21 days followed by a 7 day break Enzalutamide taken daily for 28 days
Drug: Tivozanib
Other Name: AV-951

Drug: Enzalutamide
Other Name: MDV-3100

Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 2 years ]
    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.

Secondary Outcome Measures :
  1. Safety and Tolerability [ Time Frame: 2 years ]
    Safety and tolerability of tivozanib and enzalutamide will be assessed. The number of patients having grades 1-4 adverse events by NCI CTC version 4.0 will be recorded.

  2. Overall Survival [ Time Frame: 2 years ]
    To estimate overall survival in patients treated with tivozanib and enzalutamide

  3. PSA Response rate [ Time Frame: 2 years ]
    To evaluate PSA response rate

  4. Time to PSA Progression [ Time Frame: 2 years ]
    The time to PSA progression (in months) will be evaluated in patients treated with enzalutamide and tivozanib

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Significant bleeding disorders within 6 months prior to administration of first dose of study drug
  • Psychiatric disorder or altered mental status precluding informed consent or protocol-related testing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01885949

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
National Comprehensive Cancer Network
Principal Investigator: M. Dror Michaelson, MD, PhD Massachusetts General Hospital

Responsible Party: Dror Michaelson, MD, Principal Investigator, Massachusetts General Hospital Identifier: NCT01885949     History of Changes
Other Study ID Numbers: 13-073
First Posted: June 25, 2013    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Dror Michaelson, MD, Massachusetts General Hospital:

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases