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Tivozanib + Enzalutamide in Adv Prostate Cancer

Primary Purpose

Prostate Cancer

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tivozanib

Enzalutamide

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental Treatment Arm

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Safety and Tolerability

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.

Overall Survival

To estimate overall survival in patients treated with tivozanib and enzalutamide

PSA Response rate

To evaluate PSA response rate

Time to PSA Progression

The time to PSA progression (in months) will be evaluated in patients treated with enzalutamide and tivozanib

Full Information

NCT ID

NCT01885949

First Posted

June 19, 2013

Last Updated

March 13, 2023

Sponsor

Massachusetts General Hospital

Collaborators

National Comprehensive Cancer Network

1. Study Identification

Unique Protocol Identification Number

NCT01885949

Brief Title

Tivozanib + Enzalutamide in Adv Prostate Cancer

Official Title

Phase 2 Combination Trial of Tivozanib and Enzalutamide in Men With Advanced Prostate Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 3, 2013 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

National Comprehensive Cancer Network

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Experimental Treatment Arm

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Tivozanib

Other Intervention Name(s)

AV-951

Intervention Description

Oral

Intervention Type

Drug

Intervention Name(s)

Enzalutamide

Other Intervention Name(s)

MDV-3100

Intervention Description

oral

Primary Outcome Measure Information:

Title

Progression Free Survival

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Safety and Tolerability

Description

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.

Time Frame

2 years

Title

Overall Survival

Description

To estimate overall survival in patients treated with tivozanib and enzalutamide

Time Frame

2 years

Title

PSA Response rate

Description

To evaluate PSA response rate

Time Frame

2 years

Title

Time to PSA Progression

Description

The time to PSA progression (in months) will be evaluated in patients treated with enzalutamide and tivozanib

Time Frame

2 years

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

M. Dror Michaelson, MD, PhD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Tivozanib + Enzalutamide in Adv Prostate Cancer

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