Vinflunine in Hormone Refractory Prostate Cancer (HRPC)

• Sponsor: SCRI Development Innovations, LLC (Other)
• Overall Status: Completed
• CT.gov ID: NCT00545766
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 41
• Locations: 12
• Arm: 1
• Duration (Months): 20.1
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Currently, there are no established 2nd-line or salvage chemotherapy regimens for patients with HRPC, many of whom retain an excellent performance status. The antitumor characteristics and toxicity profile of vinflunine make it an ideal agent to be investigated in this setting. In this Phase II trial, we plan to evaluate the efficacy, toxicity, and feasibility of administering IV vinflunine at a dose of 320 mg/m2 q3w as salvage chemotherapy in patients with HRPC. The patients will be evaluated for response, survival, and toxicity. If significant antitumor activity is demonstrated, further evaluation of this agent either alone or combination regimens and at earlier stages of disease will be indicated.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Vinflunine	Phase 2

Detailed Description

This is a non-randomized (single-arm), open-label, multi-center, single-agent, Phase II study of vinflunine as second- or third-line treatment of subjects with HRPC. The primary objective of the study is to evaluate the efficacy of vinflunine in the salvage treatment, as measured by Protein-Specific Antigen (PSA) Response Rate endpoint.

The primary objective of this study is as follows:

To evaluate the efficacy (as measured by the PSA response rate) of IV vinflunine administered q3w in HRPC patients who have progressed after one or two previous chemotherapy regimens.

Secondary Objectives

The secondary objectives of this study are as follows:

• To evaluate the efficacy of IV vinflunine administered q3w in HRPC patients who have previously received chemotherapy (one or two regimens), as measured by:

• Time to PSA progression

• Overall survival

• Palliative response in patients with an Analgesic Score (AS) ≥10 and stable baseline pain

• Health-Related Quality of Life

• To assess the efficacy (as measured by the PSA response rate) of IV vinflunine in HRPC patients based on their response to prior chemotherapy

• Chemotherapy responsive - previous response to most recent chemotherapy regimen lasting

2 months after completion.

• Chemotherapy refractory - failure to respond to, or progression during or within three months of completing last chemotherapy.

• To assess the response rate to IV vinflunine in the subset of patients with measurable disease, as measured by traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Therasse et al. 2000).

• To evaluate the safety of IV vinflunine administered every three weeks in HRPC patients who have previously received chemotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Vinflunine as Salvage Chemotherapy in Hormone Refractory Prostate Cancer (HRPC)
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Interventional	Drug: Vinflunine; Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.; Other Names: Javlor

Outcome Measures

Primary Outcome Measures

1. Protein-specific Antigen (PSA) Response Rate [18 months]

   Defined as the percentage of patients with an objective decrease in PSA and/or experience an objective benefit from treatment.

Secondary Outcome Measures

1. Time to PSA Progression [18 months]

   Time to PSA Progression is defined as the time from the first dose administration to the date when criteria for PSA progression (for Progressive Disease) are initially met.

2. Progression Free Survival [18 months]

   Progression free survival is defined as the time from the first day of treatment until the day tumor progression was documented. Response categories were assigned after completion of two weeks of vinflunine therapy using Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is defined as an increase in >=25% of of serum PSA above baseline value documented by at least two successive values separated by at least one week.

3. Number of Participants Experiencing Overall Survival (OS) [18 months]

   OS is defined as the time from the first treatment until date of death due to any cause. In the absence of confirmation of death or lack of data beyond follow-up period, the survival time was censored to last date the participant was known to be alive. Number of participants experiencing overall survival is reported here.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Men age 18 years of age or older who have HRPC are eligible for this study based on the following inclusion criteria:

1. Histologically confirmed adenocarcinoma of the prostate.

2. Progressive hormone refractory locally advanced or metastatic disease.

• (Definition of HRPC): Clinical or serological evidence of disease progression despite adequate anti-androgen therapy, documented by castrate levels of serum testosterone (<50 ng/mL).

• Patients on medical castration therapy should continue on treatment to maintain castrate levels of serum testosterone. Patients receiving anti-androgen or estrogen therapy should either be maintained on it, or have documented progression 4 weeks after withdrawal of all agents (except nilutamide and bicalutamide), which requires 6 weeks.

1. Disease Progression, documented by any of the following:

• PSA Progression, documented by an elevated PSA level (>5 ng/mL), which has risen serially from the baseline PSA value (PSA value #1) on two occasions, each at least 1 week apart (these will be considered PSA values #2 and #3). (Note: if the level of PSA value #3 is less than the level of PSA value #2, a subsequent PSA value must be obtained (PSA value #4) at least 1 week after PSA value #3 was measured. In order for this event to be considered a PSA progression, the level of this final PSA value (PSA value #4) must be greater than the PSA level that was observed for PSA value #2.

• Progressive metastatic prostate carcinoma, documented by computed tomography (CT), magnetic resonance imaging (MRI), or radiograph of non osseous lesions (see Section 7.2).

• Bone Scan Progression, documented by the appearance of at least one or more new lesions that are not believed to be secondary to tumor flare phenomenon.

1. Patients with bone only disease must have a PSA level >=5 ng/mL; patients with stable lesions must have evidence of PSA progression. Patients must have radiographically or clinically demonstrable metastatic disease.

2. Receipt of either 1 or 2 previous chemotherapy regimens; one of these regimens must have included docetaxel.

3. ECOG performance status of 0-2.

4. Adequate bone marrow function, defined by: white blood cells >=3,500/uL, hemoglobin

=8 g/dL, platelet count >=100,000/uL.

1. Adequate renal function, defined by: serum creatinine <1.8 mg/dL, or calculated or measured creatinine clearance (GFR) of >=60 cc/min. Patients with a creatinine clearance of >30 mL/min but <60 mL/min may also be enrolled, but will require an initial adjusted dose (see Section 5.1)

2. Adequate hepatic function, defined by: total bilirubin <1.5 x the upper limit of normal, AST <2 x the upper limit of normal.

3. Patients must be able to comprehend the nature of the study and provide written informed consent.

4. Partners of women of childbearing potential must use effective contraception while on treatment and for at least 3 months thereafter. Women of childbearing potential include females who have experienced menarche and have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not post-menopausal (i.e., amenorrhea >12 months).

5. Patients on bisphosphonate therapy (at the discretion of the investigator).

Exclusion Criteria:

1. History of other prior malignancy in the past 5 years (excluding resected basal cell or squamous cell skin cancer).

2. History of second- or third-degree heart block, uncontrolled angina, uncontrolled hypertension, or recent myocardial infarction or congestive heart failure (New York Heart Association Class III-IV) within the past 6 months (see Appendix F)

3. Cerebral vascular accident within the past 6 months.

4. Peripheral neuropathy > grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

5. Patients with rising PSA but no demonstrable metastases.

6. Previous radiotherapy, outside of standard portals, utilized for prostate cancer (if total amount of radiotherapy encompasses >25% of bone marrow containing osseous regions).

7. Prior therapy with Strontium 90, Samarium 150, or other injectable therapeutic radioisotopes.

8. History of prior allergic reaction to any vinca alkaloid.

9. Use of chemotherapy or investigational drugs within 4 weeks prior to the first dose of study drug.

10. Treatment with ketoconazole, itraconazole, ritonavir, amprenavir, or indinavir within 4 weeks prior to the first dose of study drug.

11. Previous treatment with an anthracycline.

12. Patients who are unable to receive chemotherapy on a basis of once every three weeks as a result of physical, environmental, or co existent medical problems.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
2	Integrated Community Oncology Network	Jacksonville	Florida	United States	32256
3	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
4	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
5	Consultants in Blood Disorders and Cancer	Louisville	Kentucky	United States	40207
6	Oncology Hematology Care	Cincinnati	Ohio	United States	45242
7	Consultants in Medical Oncology and Hematology	Drexel Hill	Pennsylvania	United States	19026
8	Associates in Hematology Oncology	Chattanooga	Tennessee	United States	37404
9	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
10	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37023
11	South Texas Oncology and Hematology	San Antonio	Texas	United States	78258
12	Peninsula Cancer Institute	Newport News	Virginia	United States	23601

Sponsors and Collaborators

• SCRI Development Innovations, LLC
• Bristol-Myers Squibb

Investigators

• Study Chair: John D. Hainsworth, M.D., SCRI Development Innovations, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Published article in Cancer Investigation

Publications

None provided.

• Responsible Party: SCRI Development Innovations, LLC
• ClinicalTrials.gov Identifier: NCT00545766
• Other Study ID Numbers: SCRI GU 35
• First Posted: Oct 17, 2007
• Last Update Posted: Dec 16, 2021
• Last Verified: Dec 1, 2021

• Keywords provided by SCRI Development Innovations, LLC: Prostate Cancer; Hormone Refractory; Vinflunine; Salvage Chemotherapy
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Period Title: Overall Study
STARTED	41
COMPLETED	36
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Overall Participants	41
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 17.1%
>=65 years	34 82.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72 (8.4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	41 100%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Protein-specific Antigen (PSA) Response Rate
Description	Defined as the percentage of patients with an objective decrease in PSA and/or experience an objective benefit from treatment.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Five patients did not receive two full cycles of vinflunine and were not included in the analysis

Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Measure Participants	36
Number (95% Confidence Interval) [percentage of patients]	3

2. Secondary Outcome

Title	Time to PSA Progression
Description	Time to PSA Progression is defined as the time from the first dose administration to the date when criteria for PSA progression (for Progressive Disease) are initially met.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

38 patients with serial PSA evaluations were included in the analysis. 3 patients only had baseline evaluations and were not included in analysis.

Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Measure Participants	38
Mean (Full Range) [weeks]	12.2

3. Secondary Outcome

Title	Progression Free Survival
Description	Progression free survival is defined as the time from the first day of treatment until the day tumor progression was documented. Response categories were assigned after completion of two weeks of vinflunine therapy using Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is defined as an increase in >=25% of of serum PSA above baseline value documented by at least two successive values separated by at least one week.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Measure Participants	36
Mean (95% Confidence Interval) [months]	2.1

4. Secondary Outcome

Title	Number of Participants Experiencing Overall Survival (OS)
Description	OS is defined as the time from the first treatment until date of death due to any cause. In the absence of confirmation of death or lack of data beyond follow-up period, the survival time was censored to last date the participant was known to be alive. Number of participants experiencing overall survival is reported here.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
Measure Participants	41
Count of Participants [Participants]	15 36.6%

Adverse Events

Time Frame	18 months
Arm/Group Title	Vinflunine
Arm/Group Description	Vinflunine : Vinflunine 320 mg/m2 will be administered as a 20 minute IV infusion q3w. Patients will be evaluated for toxicity after each cycle of therapy. Response to vinflunine will be assessed every 6 weeks (every 2 cycles) of treatment. A maximum of 6 cycles of therapy are planned.
All Cause Mortality
	Vinflunine
	Affected / at Risk (%)	# Events
Total	26/41 (63.4%)
Serious Adverse Events
	Vinflunine
	Affected / at Risk (%)	# Events
Total	11/41 (26.8%)
Blood and lymphatic system disorders
Hemoglobin	1/41 (2.4%)	1
Febrile neutropenia	1/41 (2.4%)	1
Cardiac disorders
Cardiac arrhythmia	1/41 (2.4%)	1
Cardiac ischemia	1/41 (2.4%)	1
Gastrointestinal disorders
Dehydration	3/41 (7.3%)	4
General disorders
Pain - abdomen	2/41 (4.9%)	2
Pain - back	1/41 (2.4%)	1
Infections and infestations
Infection - Pneumonia	1/41 (2.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progression	3/41 (7.3%)	3
Renal and urinary disorders
Renal failure	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Vinflunine
	Affected / at Risk (%)	# Events
Total	33/41 (80.5%)
Blood and lymphatic system disorders
ANC	30/41 (73.2%)	50
HGB	31/41 (75.6%)	76
PLT	13/41 (31.7%)	21
WBC	32/41 (78%)	59
Endocrine disorders
Hot flashes	4/41 (9.8%)	5
Gastrointestinal disorders
Abdominal pain	9/41 (22%)	10
Anorexia	14/41 (34.1%)	23
Constipation	22/41 (53.7%)	36
Dehydration	3/41 (7.3%)	6
Diarrhea	9/41 (22%)	9
Dyspepsia	6/41 (14.6%)	6
Nausea	17/41 (41.5%)	27
Stomatitis	2/41 (4.9%)	2
Vomiting	9/41 (22%)	11
General disorders
Fatigue	33/41 (80.5%)	72
Pain	2/41 (4.9%)	3
Weakness	9/41 (22%)	13
Weight Loss	7/41 (17.1%)	9
Infections and infestations
Febrile Neutropenia	4/41 (9.8%)	5
Infection without Neutropenia	4/41 (9.8%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	7/41 (17.1%)	9
Bone pain	11/41 (26.8%)	20
Myalgia	8/41 (19.5%)	11
Pain (back)	3/41 (7.3%)	3
Nervous system disorders
Depression	2/41 (4.9%)	4
Headache	5/41 (12.2%)	9
Sensory Neuropathy	7/41 (17.1%)	15
Renal and urinary disorders
Urinary frequency	2/41 (4.9%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/41 (19.5%)	14
Skin and subcutaneous tissue disorders
Alopecia	8/41 (19.5%)	11
Injection Site Reaction	7/41 (17.1%)	10
Rash	2/41 (4.9%)	2
Vascular disorders
Edema	6/41 (14.6%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.