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

NCT01732549 | Terminated Phase 2 Results DMC

• 2 other identifiers: 8-55-58102-0022012-001038-32
• Study Type: interventional
• Target: 144
• Locations: 11 countries
• Sites: 58

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.

Conditions

Metastatic Castrate Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Every 8 weeks until disease progression documentation (approximately up to 2.5 years)

Secondary Outcomes (7)

• Overall Survival Based on Number of Subjects Who Died

  Every 3 months after study treatment stop until death (approximately up to 2.5 years)

• Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)

  Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)

• Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death

  Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)

• Time to Further Anticancer Treatment for Prostate Cancer

  Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)

• Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)

  Up to End of Study visit (approximately up to 2.5 years)

Study Arms (2)

Tasquinimod

EXPERIMENTAL

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.

Drug: Tasquinimod

Placebo

PLACEBO COMPARATOR

1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.

Drug: Placebo

Interventions

Tasquinimod DRUG

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.

Tasquinimod

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ipsen: lead

Study Sites (58)

AZ Maria Middelares

Ghent, Belgium

Location

UZ Gent

Ghent, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Roeselare, Belgium

Location

Unknown Facility

Prague, Hradčany, Czechia

Location

Unknown Facility

Prague, Libeň, Czechia

Location

Unknown Facility

Brno, Czechia

Location

Unknown Facility

Olomouc, Czechia

Location

Unknown Facility

Prague, Czechia

Location

Unknown Facility

Aalborg, Denmark

Location

Unknown Facility

Aarhus, Denmark

Location

Unknown Facility

Copenhagen, Denmark

Location

Unknown Facility

Herlev, Denmark

Location

Unknown Facility

Angers, France

Location

Unknown Facility

Bordeaux, France

Location

Unknown Facility

Clermont-Ferrand, France

Location

Unknown Facility

Dijon, France

Location

Unknown Facility

Lille, France

Location

Besancon

Lyon, France

Location

Centre Leon Berard

Lyon, France

Location

Hopital Edouard Herriot

Lyon, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Saint-Herblain, France

Location

Unknown Facility

Toulouse, France

Location

Unknown Facility

Villejuif, France

Location

Unknown Facility

Aachen, Germany

Location

Unknown Facility

Essen, Germany

Location

Unknown Facility

München, Germany

Location

Unknown Facility

Nürtingen, Germany

Location

Unknown Facility

Tübingen, Germany

Location

Bajcsy-Zsilinszky Kórház

Budapest, Hungary

Location

Országos Onkológia Intézet

Budapest, Hungary

Location

Uzsoki utcai Kórház

Budapest, Hungary

Location

Unknown Facility

Genova, Italy

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Modena, Italy

Location

Unknown Facility

Pavia, Italy

Location

Unknown Facility

Roma, Italy

Location

Unknown Facility

Rozzano, Italy

Location

Unknown Facility

Torino, Italy

Location

Unknown Facility

Kaunas, Lithuania

Location

Unknown Facility

Vilnius, Lithuania

Location

Unknown Facility

Gdansk, Poland

Location

Unknown Facility

Gdynia, Poland

Location

Unknown Facility

Olsztyn, Poland

Location

Urology and Urological Oncology Department and Clinic

Wroclaw, Poland

Location

Wojewódzki Szpital Specjalistyczny we Wrocławiu

Wroclaw, Poland

Location

Hospital Clinic Vllarroel

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Valle de Hebrón

Barcelona, Spain

Location

Unknown Facility

Elche, Spain

Location

Unknown Facility

Sabadell, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

Leeds, United Kingdom

Location

Guy's & St Thomas NHS Foundation

London, United Kingdom

Location

The Royal Marsden NHS Trust

London, United Kingdom

Location

University College Hospitals London

London, United Kingdom

Location

Unknown Facility

Sutton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29059273 DERIVED

MeSH Terms

Interventions

tasquinimod

Limitations and Caveats

The study was terminated early due to the stop of the project as decided by sponsor. The trial included number of planned patients \& number of events(PFS)were met to draw conclusions. Only follow-up of patients were discontinued earlier than planned.

Results Point of Contact

• Title: Medical Director, Oncology
• Organization: Ipsen

clinical.trials@ipsen.com

clinical.trials@ipsen.com

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2012
• First Posted: November 26, 2012
• Study Start: January 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 22, 2019
• Results First Posted: October 3, 2016

Record last verified: 2019-11

Locations

FR (12); DE (5); BE (4); LI (2); PL (5); GB (5); DK (4); HU (3); ES (6); CZ (5); IT (7)