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

• ClinicalTrials.gov Identifier: NCT01732549
• Recruitment Status: Terminated
• First Posted: November 26, 2012
• Results First Posted: October 3, 2016
• Last Update Posted: November 22, 2019
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

Tracking Information

• First Submitted Date: October 24, 2012
• First Posted Date: November 26, 2012
• Results First Submitted Date: April 29, 2016
• Results First Posted Date: October 3, 2016
• Last Update Posted Date: November 22, 2019
• Study Start Date: January 2013
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2016)

Time to Radiological Progression Free Survival [PFS] [ Time Frame: Every 8 weeks until disease progression documentation (approximately up to 2.5 years) ]

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.

Original Primary Outcome Measures (submitted: November 19, 2012)

Time to Radiological Progression Free Survival [PFS] [ Time Frame: Every 8 weeks, up to 3.5 years ]

The time from the date of randomisation to the date of radiological progression or death due to any cause.

Current Secondary Outcome Measures (submitted: August 9, 2016)

• Overall Survival Based on Number of Subjects Who Died [ Time Frame: Every 3 months after study treatment stop until death (approximately up to 2.5 years) ]
  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) [ Time Frame: Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years) ]
  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 [ Time Frame: Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years) ]
  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 Frame: Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years) ]
  Time from randomisation to further treatment for prostate cancer
• Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P) [ Time Frame: Up to End of Study visit (approximately up to 2.5 years) ]
  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 [ Time Frame: Baseline and End-of-study Visit (approximately up to 2.5 years) ]
  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 [ 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) ]
  Number of subjects reporting adverse events

Original Secondary Outcome Measures (submitted: November 19, 2012)

• Overall survival [ Time Frame: Every 8 weeks, up to 3.5 years ]
  Overall survival is defined as the time from randomisation to death due to any cause
• Time to progression free survival [PFS] on next-line therapy (PFS 2) [ Time Frame: Every 8 weeks, up to 3.5 years ]
  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.
• Symptomatic PFS [ Time Frame: Every 8 weeks, up to 3.5 years ]
  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)
• Safety Profile of Tasquinimod [ Time Frame: Every 8 weeks, up to 3.5 years ]
  Number of subjects reporting adverse events

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Metastatic Castrate Resistant Prostate Cancer

Intervention

• Drug: Tasquinimod
  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.
• Drug: Placebo
  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

Study Arms

• Experimental: Tasquinimod
  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.
  Intervention: Drug: Tasquinimod
• Placebo Comparator: Placebo
  1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.
  Intervention: Drug: Placebo

• Publications *: Fizazi K, Ulys A, Sengeløv 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 9, 2016): 144
• Original Estimated Enrollment (submitted: November 19, 2012): 140
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czechia, Denmark, France, Germany, Hungary, Italy, Lithuania, Poland, Spain, United Kingdom
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT01732549
• Other Study ID Numbers: 8-55-58102-002; 2012-001038-32 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Ipsen
• Study Sponsor: Ipsen
• Collaborators: Not Provided

Investigators

• Study Director: Ipsen Medical Director; Ipsen

• PRS Account: Ipsen
• Verification Date: November 2019