Back to resultsA Proof of Concept Study of Maintenance Therapy With Tasquinimod in Patients With Metastatic Castrate-resistant Prostate Cancer Who Are Not Progressing After a First Line Docetaxel Based Chemotherapy
Primary Purpose
Metastatic Castrate Resistant Prostate Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tasquinimod
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Castrate Resistant Prostate Cancer
Eligibility Criteria
Inclusion Criteria:
- Histologically documented prostate cancer with evidence of metastatic disease on radiological evaluation, with or without symptoms (defined according to the BPI scale, with use of analgesics or narcotics)
- Has received a first line docetaxel based chemotherapy (as a monotherapy) every 3 weeks schedule of administration with corticosteroids for a minimum of 6 cycles with a cumulative dose ≥360 mg/m2. Any combination with investigational or non investigational agent is prohibited
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Docetaxel-related adverse effects must have been resolved to NCI-CTCAE v4.03 (Common Toxicity Criteria for Adverse Effects) Grade ≤1. Chemotherapy-induced alopecia and Grade 2 peripheral neuropathy are allowed
- No progressive disease at the end of docetaxel treatment defined according to RECIST criteria, no new lesion(s) assessed by bone scan and no elevated prostate specific antigen (PSA) for the three last tests with PSA3≤PSA2≤PSA1. The time between each PSA test should be preferably at least 14 days, however, a minimum of 7 days is acceptable.
Note: PSA value can be rounded to the nearest whole number if PSA>10 ng/mL. If the PSA3 value is above the PSA2, a fourth PSA test will be performed. The PSA4 value should be below or equal to PSA2
- Last dose of docetaxel administered between 21 and 42 days before randomisation
- Chemical or surgical castration verified by levels of serum testosterone ≤50 ng/dL (1.75 nmol/L)
Exclusion Criteria:
- Has concurrent use of other anticancer agents or treatments, with the following exceptions: ongoing treatment with luteinising hormone-releasing hormone agonists or antagonists, denosumab or bisphosphonate (e.g., zoledronic acid) is permitted if started ≥4 weeks prior to Screening. Ongoing treatment should be kept at a stable dose regimen
- Has ongoing treatment with warfarin
- Had prior radiation therapy since starting docetaxel. Exceptions may be made for palliative non-myelosuppressive radiation therapy administered more than 2 weeks prior to randomisation
- Had prior strontium, samarium or radium therapy or prior treatment with tasquinimod, or any agents with antiangiogenic properties
- Has ongoing treatment with corticosteroids at >10 mg/day prednisolone equivalent
- Has prostate cancer pain that warrants the initiation of radiotherapy or chemotherapy
- Has known brain or epidural metastases. Patients with previous medullary cord compression without any neurological deficit could be included
- Has a history of other malignancies, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated, without evidence of disease for >5 years
Sites / Locations
- AZ Maria Middelares
- UZ Gent
- Besancon
- Centre Leon Berard
- Hopital Edouard Herriot
- Bajcsy-Zsilinszky Kórház
- Országos Onkológia Intézet
- Uzsoki utcai Kórház
- Urology and Urological Oncology Department and Clinic
- Wojewódzki Szpital Specjalistyczny we Wrocławiu
- Hospital Clinic Vllarroel
- Hospital del Mar
- Hospital Valle de Hebrón
- Guy's & St Thomas NHS Foundation
- The Royal Marsden NHS Trust
- University College Hospitals London
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tasquinimod
Placebo
Arm Description
1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg or 1 mg per day) until disease progression or toxicity or patient's willingness to stop.
1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.
Outcomes
Primary Outcome Measures
Time to Radiological Progression Free Survival [PFS]
The time from the date of randomisation to the date of radiological progression or death due to any cause.
Radiological progression was defined
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
Secondary Outcome Measures
Overall Survival Based on Number of Subjects Who Died
Overall survival is defined as the time from randomisation to death due to any cause.
The number of participants who died is presented since the Median was not reached for this assessment.
Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73
Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)
The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause.
Radiological progression was defined
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death
Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use].
Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events.
The median symptomatic PFS for placebo and tasquinimod groups was not reached.
Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73
Time to Further Anticancer Treatment for Prostate Cancer
Time from randomisation to further treatment for prostate cancer
Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
End of Study visit (within 14 days of last dose of study treatment)
Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P
The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)
Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score
Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment)
The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to "the worst health you can imagine", and the highest rate(100) corresponds to "the best health you can imagine"
Safety Profile of Tasquinimod
Number of subjects reporting adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01732549
Brief Title
A Proof of Concept Study of Maintenance Therapy With Tasquinimod in Patients With Metastatic Castrate-resistant Prostate Cancer Who Are Not Progressing After a First Line Docetaxel Based Chemotherapy
Official Title
A Randomised, Double-Blind, Placebo-Controlled Proof Of Concept Study Of Maintenance Therapy With Tasquinimod In Patients With Metastatic Castrate-Resistant Prostate Cancer Who Are Not Progressing After A First Line Docetaxel Based Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Why Stopped
Development of tasquinimod in prostate cancer discontinued
Study Start Date
January 2013 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
May 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to confirm that tasquinimod used as maintenance therapy is active and tolerable in patients with metastatic castrate-resistant prostate cancer not progressing after a first chemotherapy with docetaxel.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castrate Resistant Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
144 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tasquinimod
Arm Type
Experimental
Arm Description
1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg or 1 mg per day) until disease progression or toxicity or patient's willingness to stop.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.
Intervention Type
Drug
Intervention Name(s)
Tasquinimod
Intervention Description
A patient's dose will escalate from one level to the next, once tolerability of the current dose is established. If tolerability issues arise at 0.5 or 1 mg/day, patients will have their dose reduced to 0.25 or 0.5 mg/day, respectively.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules are identical to tasquinimod capsules in appearance and excipients but exclude the active compound (tasquinimod), to be taken orally once a day with water and food
Primary Outcome Measure Information:
Title
Time to Radiological Progression Free Survival [PFS]
Description
The time from the date of randomisation to the date of radiological progression or death due to any cause.
Radiological progression was defined
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
Time Frame
Every 8 weeks until disease progression documentation (approximately up to 2.5 years)
Secondary Outcome Measure Information:
Title
Overall Survival Based on Number of Subjects Who Died
Description
Overall survival is defined as the time from randomisation to death due to any cause.
The number of participants who died is presented since the Median was not reached for this assessment.
Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73
Time Frame
Every 3 months after study treatment stop until death (approximately up to 2.5 years)
Title
Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)
Description
The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause.
Radiological progression was defined
- Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions.
Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
- Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
Time Frame
Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)
Title
Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death
Description
Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use].
Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events.
The median symptomatic PFS for placebo and tasquinimod groups was not reached.
Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73
Time Frame
Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)
Title
Time to Further Anticancer Treatment for Prostate Cancer
Description
Time from randomisation to further treatment for prostate cancer
Time Frame
Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)
Title
Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Description
End of Study visit (within 14 days of last dose of study treatment)
Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P
The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)
Time Frame
Up to End of Study visit (approximately up to 2.5 years)
Title
Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score
Description
Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment)
The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to "the worst health you can imagine", and the highest rate(100) corresponds to "the best health you can imagine"
Time Frame
Baseline and End-of-study Visit (approximately up to 2.5 years)
Title
Safety Profile of Tasquinimod
Description
Number of subjects reporting adverse events
Time Frame
At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically documented prostate cancer with evidence of metastatic disease on radiological evaluation, with or without symptoms (defined according to the BPI scale, with use of analgesics or narcotics)
Has received a first line docetaxel based chemotherapy (as a monotherapy) every 3 weeks schedule of administration with corticosteroids for a minimum of 6 cycles with a cumulative dose ≥360 mg/m2. Any combination with investigational or non investigational agent is prohibited
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Docetaxel-related adverse effects must have been resolved to NCI-CTCAE v4.03 (Common Toxicity Criteria for Adverse Effects) Grade ≤1. Chemotherapy-induced alopecia and Grade 2 peripheral neuropathy are allowed
No progressive disease at the end of docetaxel treatment defined according to RECIST criteria, no new lesion(s) assessed by bone scan and no elevated prostate specific antigen (PSA) for the three last tests with PSA3≤PSA2≤PSA1. The time between each PSA test should be preferably at least 14 days, however, a minimum of 7 days is acceptable.
Note: PSA value can be rounded to the nearest whole number if PSA>10 ng/mL. If the PSA3 value is above the PSA2, a fourth PSA test will be performed. The PSA4 value should be below or equal to PSA2
Last dose of docetaxel administered between 21 and 42 days before randomisation
Chemical or surgical castration verified by levels of serum testosterone ≤50 ng/dL (1.75 nmol/L)
Exclusion Criteria:
Has concurrent use of other anticancer agents or treatments, with the following exceptions: ongoing treatment with luteinising hormone-releasing hormone agonists or antagonists, denosumab or bisphosphonate (e.g., zoledronic acid) is permitted if started ≥4 weeks prior to Screening. Ongoing treatment should be kept at a stable dose regimen
Has ongoing treatment with warfarin
Had prior radiation therapy since starting docetaxel. Exceptions may be made for palliative non-myelosuppressive radiation therapy administered more than 2 weeks prior to randomisation
Had prior strontium, samarium or radium therapy or prior treatment with tasquinimod, or any agents with antiangiogenic properties
Has ongoing treatment with corticosteroids at >10 mg/day prednisolone equivalent
Has prostate cancer pain that warrants the initiation of radiotherapy or chemotherapy
Has known brain or epidural metastases. Patients with previous medullary cord compression without any neurological deficit could be included
Has a history of other malignancies, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated, without evidence of disease for >5 years
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
AZ Maria Middelares
City
Gent
Country
Belgium
Facility Name
UZ Gent
City
Gent
Country
Belgium
City
Leuven
Country
Belgium
City
Roeselare
Country
Belgium
City
Praha
State/Province
Hradčany
Country
Czechia
City
Praha
State/Province
Libeň
Country
Czechia
City
Brno
Country
Czechia
City
Olomouc
Country
Czechia
City
Prague 2
Country
Czechia
City
Aalborg
Country
Denmark
City
Aarhus
Country
Denmark
City
Herlev
Country
Denmark
City
København
Country
Denmark
City
Angers
Country
France
City
Bordeaux
Country
France
City
Clermont Ferrand
Country
France
City
Dijon
Country
France
City
Lille
Country
France
Facility Name
Besancon
City
Lyon
Country
France
Facility Name
Centre Leon Berard
City
Lyon
Country
France
Facility Name
Hopital Edouard Herriot
City
Lyon
Country
France
City
Paris
Country
France
City
St Herblain
Country
France
City
Toulouse
Country
France
City
Villejuif
Country
France
City
Aachen
Country
Germany
City
Essen
Country
Germany
City
München
Country
Germany
City
Nürtingen
Country
Germany
City
Tübingen
Country
Germany
Facility Name
Bajcsy-Zsilinszky Kórház
City
Budapest
Country
Hungary
Facility Name
Országos Onkológia Intézet
City
Budapest
Country
Hungary
Facility Name
Uzsoki utcai Kórház
City
Budapest
Country
Hungary
City
Genova
Country
Italy
City
Milano
Country
Italy
City
Modena
Country
Italy
City
Pavia
Country
Italy
City
Roma
Country
Italy
City
Rozzano
Country
Italy
City
Torino
Country
Italy
City
Kaunas
Country
Lithuania
City
Vilnius
Country
Lithuania
City
Gdansk
Country
Poland
City
Gdynia
Country
Poland
City
Olsztyn
Country
Poland
Facility Name
Urology and Urological Oncology Department and Clinic
City
Wroclaw
Country
Poland
Facility Name
Wojewódzki Szpital Specjalistyczny we Wrocławiu
City
Wroclaw
Country
Poland
Facility Name
Hospital Clinic Vllarroel
City
Barcelona
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Valle de Hebrón
City
Barcelona
Country
Spain
City
Elche
Country
Spain
City
Sabadell
Country
Spain
City
Valencia
Country
Spain
City
Leeds
Country
United Kingdom
Facility Name
Guy's & St Thomas NHS Foundation
City
London
Country
United Kingdom
Facility Name
The Royal Marsden NHS Trust
City
London
Country
United Kingdom
Facility Name
University College Hospitals London
City
London
Country
United Kingdom
City
Sutton
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29059273
Citation
Fizazi K, Ulys A, Sengelov L, Moe M, Ladoire S, Thiery-Vuillemin A, Flechon A, Guida A, Bellmunt J, Climent MA, Chowdhury S, Dumez H, Matouskova M, Penel N, Liutkauskiene S, Stachurski L, Sternberg CN, Baton F, Germann N, Daugaard G. A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy. Ann Oncol. 2017 Nov 1;28(11):2741-2746. doi: 10.1093/annonc/mdx487.
Results Reference
derived
Learn more about this trial
A Proof of Concept Study of Maintenance Therapy With Tasquinimod in Patients With Metastatic Castrate-resistant Prostate Cancer Who Are Not Progressing After a First Line Docetaxel Based Chemotherapy
We'll reach out to this number within 24 hrs