Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer

Prostatic Neoplasms, Castration-Resistant Clinical Trial

— TasQ003  

Official title:

A Phase III, Randomised, Double-Blind, Placebo-Controlled Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02057666
• Other study ID #: 8-55-58102-003
• Status: Terminated
• Phase: Phase 3
• Start date: January 2014
• Est. completion date: May 2015

Study information

• Verified date: March 2021
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective was to confirm the effect of tasquinimod in delaying disease progression or death as compared with placebo in chemo-naïve patients with metastatic castrate-resistant prostate cancer (mCRPC). Secondary objectives included further evaluation of the safety profile of tasquinimod, comparison of clinical benefits (such as overall survival and symptoms) of tasquinimod with placebo, to evaluate the quality of life impact and to determine the pharmacokinetics of tasquinimod.

Description:

The study involved a 4-week Screening Period, Baseline Visit (Day 1) where the patient was randomised, followed by a Double Blind Treatment Period. Patients initially received tasquinimod (or corresponding placebo) at a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively. The Double Blind Treatment Period continued until the death of the patient or any criterion for withdrawal from study treatment was reached. Any placebo treated patients with radiological disease progression confirmed by the central imaging assessment, who remained asymptomatic or mildly symptomatic were, at the Investigator's discretion, given the option to continue on active treatment (tasquinimod) during an Open-Label Treatment Period, following the same titration rule described above until progression under active treatment. All other patients stopped study treatment. An End-of-Study Treatment/Withdrawal Visit was to be performed within 14 days after the last dose of study treatment and patients were then to be followed up every 6 months until 80% of the patients had died or 2 years after the last patient was randomised, whichever occurred last. A PK ancillary study was to be performed in a subgroup of 12 Asian-Chinese patients before randomisation; however, due to the early termination of this study, only some samples were analysed and no PK analyses were performed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 146
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Asian male aged at least 20 years at the time of signing the informed consent form.

2. Histologically confirmed diagnosis of adenocarcinoma of the prostate.

3. Evidence of metastatic disease (bone and/or visceral), excluding node lesion only, on radiographic examination, whether from bone scan (bone lesions) or other imaging modality (CT scan/MRI).

4. Chemical or surgical castration verified by levels of serum testosterone =50 ng/dL (1.75 nmol/L).

5. Evidence of progressive disease after castration levels of testosterone had been

achieved, defined by any of the following criteria:

• Increasing serum Prostate Specific Antigen (PSA) levels, with the most recent value =2 ng/mL (increasing levels must have been confirmed by three consecutive PSA measurements, within 15 months prior to the start of study treatment. The time between each PSA test should have been preferably at least 14 days, however a minimum of 7 days was acceptable. The third value was used for study selection).
• Progression of soft tissue metastasis documented within 6 weeks prior to randomisation (CT scan or MRI).
• Progression of bone disease (at least one new bone lesion as measured by bone scan within the 12 weeks prior to the start of study treatment).

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

7. Laboratory values as follows:

• Haemoglobin =90 g/L (=9 g/dL).
• Absolute neutrophil count =1500/µL.
• Platelets =100,000/µL.
• Serum creatinine =1.5 times the upper limit of normal (ULN).
• Total bilirubin =1.5 times ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3 times ULN (=5 times ULN if liver metastases were present).
• Serum amylase =ULN (if serum amylase >ULN, pancreatic amylase and serum lipase should have been analysed. If both pancreatic amylase and serum lipase were >ULN, patient excluded).

8. If sexually active with partner of childbearing potential, patient agreed to use adequate contraceptive method (barrier contraceptive with spermicide) while receiving study treatment and until 14 days after the stop of study treatment or had been previously vasectomised.

9. No evidence (within last 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).

10. Able to swallow and retain oral medication.

11. Able to adhere to the study visit schedule and other protocol requirements.

12. Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the Investigator and to comply with the requirements of the entire study.

13. Able to sign and date the written informed consent after being informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information.

Exclusion Criteria:

1. Cytotoxic chemotherapy for the treatment of prostate cancer within 2 years prior to the start of study treatment.

2. Previous anticancer therapy using radiation, biologics or vaccines and including sipuleucel-T (Provenge®) within 4 weeks prior to the start of study treatment and abiraterone, TAK700 or MDV3100 within 2 weeks prior to the start of study treatment. Before inclusion, abiraterone, TAK700 or MDV3100 related adverse effect must have been resolved to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade =1. If radiation therapy was applied after Baseline scan, a new Baseline scan needed to be done at least 4 weeks after the radiation therapy.

3. Therapy with antiandrogens within 4 weeks (within 6 weeks for bicalutamide e.g. Casodex®) prior to the start of study treatment.

4. Concurrent use of other anticancer agents or treatments, with the exception of ongoing treatment with luteinising hormone-releasing hormone (LHRH) agonists or antagonists, denosumab (Prolia®) or bisphosphonate (e.g. zoledronic acid), which were allowed. Ongoing treatment was to be kept at a stable schedule; however, if medically required, a change of dose, compound, or both was allowed.

5. Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.

6. Prostate cancer pain that required ongoing treatment with narcotic analgesics or warranted the initiation of radio- or chemotherapy.

7. Both of the following criteria:

• Visceral metastasis.
• Bone lesions both on and outside of the spinal axis.

8. PSA >100 ng/mL.

9. Ongoing treatment with warfarin.

10. Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days.

11. Systemic exposure to ketoconazole or other strong cytochrome P450 (CYP) 3A4 isozyme inhibitors or inducers within 14 days prior to the start of study treatment. Systemic exposure to amiodarone was not allowed within 1 year prior to the start of study treatment.

12. Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment.

13. Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment.

14. Simultaneous participation in any other study involving treatment with investigational drugs or having received treatment with investigational drugs less than 4 weeks prior to the start of study treatment.

15. Myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, New York Heart Association (NYHA) class III/IV congestive heart failure, cerebrovascular accident, transient ischaemic attack, or limb claudication at rest, within 6 months prior to start of study treatment, history of venous thrombo-embolic disease within 3 months prior to randomisation and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and uncontrolled atrial or ventricular arrhythmias.

16. History of pancreatitis.

17. Known brain or epidural metastases.

18. Known positive serology for human immunodeficiency virus (HIV) (patients with known history of HIV were excluded because of potential for unforeseen toxicity and morbidity in an immunocompromised host).

19. Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of a chronic viral hepatitis or known viral hepatitis carrier (patients who had recovered from hepatitis were allowed to enter the study) with abnormal liver function.

20. Patients with active tuberculosis (TB), or with known, untreated latent TB (country-specific TB therapy should have been given for at least 30 days prior to the start of study treatment and the patient should have intended to complete the entire course of that therapy).

21. Any condition, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could have confounded the ability to interpret data from the study or placed the patient at unacceptable risk if he participated in the study.

22. Any patient who in the opinion of the Investigator should not have participated in the study.

Related Conditions & MeSH terms

• Prostatic Neoplasms
• Prostatic Neoplasms, Castration-Resistant

Intervention

Drug:
• Tasquinimod
A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.
• Placebo
Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).

Locations

Country	Name	City	State
China	Beijing Chao-Yang Hospital Capital Medical University	Beijing	Beijing
China	Beijing Friendship Hospital Capital Medical University	Beijing	Beijing
China	Beijing Hospital of Ministry of Health	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	General Hospital Chengdu Military Region of PLA	Chengdu	Sichuan
China	Sichuan Academy of Sichuan Medical Sciences & Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Southwest Hospital (the First Affiliated Hospital of Third Military Medical University PLA)	Chongqing	Chongqing
China	Guangshou First People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital College of Medicine Zhujiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Huadong Hospital Fudan University	Shanghai	Shanghai
China	Huashan Hospital Fudan University	Shanghai	Shanghai
China	Ruijin Hospital Shanghai Jiaotong University of Medicine	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai	Shanghai
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
Korea, Republic of	Chungbuk National University Hospital	Cheongju	Chungcheong Province
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

China,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Radiological Progression-Free Survival (PFS)	PFS was defined as the time from the date of randomisation to the date of radiological progression (confirmed by the central imaging assessment) or death due to any cause. Radiological progression was defined by any of the following criteria: progression of soft tissue lesions evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 criteria; progression of bone lesions detected with bone scan according to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria; or radiologically confirmed spinal cord compression or pathological fracture due to malignant progression.; The primary endpoint was centrally and independently evaluated.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Secondary	Overall Survival	An overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.	From randomisation up to 3 years
Secondary	Local Assessment of Radiological PFS	The Investigator was to evaluate radiological disease progression in accordance with the criteria defined for the primary endpoint.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years
Secondary	Time to Symptomatic PFS Based on Local Assessment	Symptomatic PFS, defined as the time from the date of randomisation to the date of appearance of pain (using pain visual analogue scale (VAS)) at a site with documented disease and analgesic use, or skeletal-related events, or death due to prostate cancer, whichever occurred first.	Every 3 months
Secondary	Time From Randomisation to Further Treatment for Prostate Cancer	The need for any anti-tumour prostate cancer treatments was to be recorded during the Follow-up Period, with the time to further treatment to subsequently be derived.	Every 6 months during the follow-up period
Secondary	Quality of Life (QoL)	QoL measured by the Functional Assessment of Cancer Therapy Prostate Module (FACT-P) questionnaire and by the EuroQol 5-Dimension QoL Instrument (EQ-5D).; Due to the early termination of the study, a simplified data analysis (primary endpoint and overall survival) was performed to fulfil the requirement from regulatory authorities for early termination studies. Therefore, no analyses were performed on this secondary efficacy endpoint.	Every 3 months
Secondary	Tasquinimod Pharmacokinetic (PK) Profile	Tasquinimod PK profile: Following a single 1 mg dose of tasquinimod given to a subgroup of 12 Asian-Chinese patients (ancillary study).; At steady state conditions based on limited sampling strategy.; Following termination of the study the PK analyses were not performed.	Up to 216 hours after a single dose and during the double blind treatment period (Day 15, 29, 57 and 127)