A Study With Tasquinimod Treating Patients With Hepatocellular, Ovarian, Renal Cell and Gastric Cancers

NCT01743469 | Completed Phase 2 Results DMC

• 2 other identifiers: 8-55-58102-0042012-002326-75
• Study Type: interventional
• Target: 201
• Locations: 5 countries
• Sites: 24

Brief Summary

This was an exploratory proof of concept study to determine the clinical activity of tasquinimod in patients with advanced or metastatic hepatocellular carcinoma, ovarian carcinoma, renal cell carcinoma and gastric carcinoma who had progressed after standard therapies.

Conditions

Advanced or Metastatic Hepatocellular Cancer; Advanced or Metastatic Ovarian Cancer; Metastatic Renal Cell Cancer; Advanced or Metastatic Gastric Carcinoma

Keywords

Advanced; Metastatic; Hepatocellular cancer; Ovarian cancer; Renal cell cancer; Gastric carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) Rate, Defined as the Percentage of Patients Who Had Neither Progressed Nor Died as Measured by Centrally Analysed RECIST v1.1 (All Cohorts).

  Progression (prog.) defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in sum of longest diameter of target lesions,or a measurable increase in a nontarget lesion,or appearance of new lesions. 'Progressed or Died' when time between start of study drug \&first date of the following events was ≤ to analysis timepoint +3 days:1) Disease prog. according to central review using RECIST v1.1:date of disease prog. or if missing,first exam date of the visit showing a disease prog.2) Death due to any cause. 'Neither progressed, nor died' if central assessment by RECIST v1.1 confirmed no disease prog. was observed at the considered timepoint,i.e. time between start of study medication \&last examination/visit date of complete response (CR),partial response (PR) or stable disease (SD) ≥ analysis timepoint 7days.In other cases, such as patient withdrawal due to AEs without tumor assessment proving prog.,the patient was considered as 'not assessable'.

  Week 12 (Gastric Carcinoma Cohort); Week 16 (Hepatocellular and Renal Cell Carcinoma Cohorts); Week 24 (Ovarian Carcinoma Cohort).

Secondary Outcomes (10)

• PFS Rate Measured by Choi Criteria (Hepatocellular Carcinoma Cohort).

  Week 16.

• Best Overall Response and Response Rates (All Cohorts) Using RECIST v1.1 (Centrally and Locally Analysed).

  Every 6 weeks until Week 24, thereafter, every 8 weeks until disease progression, up to 36 months (gastric carcinoma cohort); every 8 weeks until disease progression, up to 36 months (all other cohorts).

• Best Overall Response and Response Rate Based on Choi Criteria (Hepatocellular Carcinoma Cohort).

  Every 8 weeks until disease progression, up to 36 months.

• Clinical Benefit (All Cohorts).

  Every 6 weeks until Week 24, thereafter, every 8 weeks until disease progression, up to 36 months (gastric carcinoma cohort); every 8 weeks until disease progression, up to 36 months (all other cohorts).

• PFS From First Study Treatment to Progression or Death Due to Any Cause Based on Choi Criteria (Hepatocellular Carcinoma Cohort).

  Every 8 weeks until disease progression, up to 36 months.

Study Arms (4)

Hepatocellular Carcinoma Cohort

EXPERIMENTAL

1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.

Drug: Tasquinimod

Ovarian Carcinoma Cohort

EXPERIMENTAL

1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.

Drug: Tasquinimod

Renal Cell Carcinoma Cohort

EXPERIMENTAL

1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.

Drug: Tasquinimod

Gastric Carcinoma Cohort

EXPERIMENTAL

1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.

Drug: Tasquinimod

Interventions

Tasquinimod DRUG

1 capsule: initially at 0.5 mg/day, increasing to 1 mg/day, maintaining 0.5 mg/day or decreasing to 0.25 mg/day after at least 2 weeks.

Also known as: ABR-215050

Hepatocellular Carcinoma Cohort

Eligibility Criteria

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

You may qualify if:

• Able and willing to provide written informed consent and to comply with the study protocol and procedures.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy greater than 3 months in the Investigator's opinion.
• Disease progression during or after previous cancer treatment.
• Measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria (v1.1).
• The following time must have elapsed between previous therapy for cancer and first administration of tasquinimod:
• At least 2 weeks since previous systemic targeted therapy with small molecule inhibitors, which included any tyrosine-kinase inhibitor.
• At least 4 weeks since the last dose of systemic anti-cancer therapy other than targeted therapy, which included cytotoxic agents, monoclonal antibody therapy, immunotherapy and prior radiotherapy.
• At least 1 week since prior hormonal therapy.
• At least 3 months since prior interferon therapy.
• Recovery to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies.
• At least 4 weeks since any major surgery or open biopsy and 7 days since a core biopsy before first study treatment.
• Adequate renal function:
• Creatinine ≤1.5 times upper limit of normal (ULN) or calculated creatinine clearance (CrCl) using the Cockcroft Gault formula ≥60 mL/min, or CrCl ≥60 mL/min.

You may not qualify if:

• Other primary malignancy within the past 3 years (except for fully-resected non-melanoma skin cancer, localised prostate cancer with normal prostate specific antigen level, or cervical cancer in situ).
• Known central nervous system metastasis that was symptomatic and/or required treatment.
• Malabsorption (other than in patients with gastric carcinoma and partial or complete gastrectomy) or intestinal obstruction.
• History of pancreatitis.
• Essential medications that are known potent inhibitors or inducers of CYP3A4.
• Ongoing treatment with CYP1A2 (including warfarin) or CYP3A4 metabolised drug substance with narrow therapeutic range at the start of study. Treatment with low molecular weight heparin (LMWH) was permitted.
• History of myocardial infarction, unstable angina, congestive heart failure New York Heart Association class III/IV, cerebrovascular accident, transient ischaemic attack, limb claudication at rest in the previous 6 months, or ongoing symptomatic dysrhythmias, or uncontrolled atrial, or ventricular arrhythmias, or uncontrolled hypertension defined as systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90 mmHg.
• Evidence of bleeding diathesis or known coagulopathy.
• History of venous thromboembolic disease within 3 months prior to first administration of study treatment.
• The patient had current, severe and uncontrolled medical condition such as infection, diabetes mellitus or other systemic disease.
• Any condition or illness that, in the opinion of the Investigator or the medical monitor, would have compromised patient safety or interfered with the evaluation of the safety of the drug.
• Had known positive serology for human immunodeficiency virus.
• Investigational drug within 28 days or within five times the elimination half-life (whichever was longest) prior to first dose of study treatment.
• Known allergy to treatment medication or its excipients.
• Breastfeeding.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (24)

Antwerp University Hospital, Wilrijkstraat 10

Edegem, 2650, Belgium

Location

Ghent University Hospital, 1K12 IE, De Pintelaan 185

Ghent, 9000, Belgium

Location

Leuven cancer institute (LKI), Herestraat

Leuven, 3000, Belgium

Location

Juravinski Cancer Centre, 699 Concession St

Hamilton, Ontario, L8V 5C2, Canada

Location

London Health Sciences Center, 790 Commissoners Road East

London, Ontario, N6A 4L6, Canada

Location

Sunnybrook, 2075 Bayview Avenue, Suite T2049

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret, 610 University Avenue

Toronto, Ontario, M5G 2M9, Canada

Location

Hospital Beaujon, 100 Blvd du Général Leclerc

Clichy, 92110, France

Location

Centre Oscar Lambret, 3 rue Frédéric Combemale

Lille, 59020, France

Location

Bureau d'Etudes Cliniques du Centre Léon Bérard, 28, rue Laennec

Lyon, 69008, France

Location

Hospital Saint-Antoine, 184 rue du Faubourg St Antoine

Paris, 75012, France

Location

Hopital Europeen Georges-Pompidou, AP-HP, 20 Rue Leblanc

Paris, 75015, France

Location

Centre Eugene Marquis, Avenue bataille Flandres Dunkerque

Rennes, 35042, France

Location

Centre René Gauducheau, Boulevard Jacques Monod

Saint-Herblain, 44805, France

Location

Institute Gustave-Roussy, 114 rue Edouard Vaillant

Villejuif, 94805, France

Location

Hospital del mar, Paseo Maritimo 25-29

Barcelona, 08003, Spain

Location

Hospital Gregorio Marañon, Dr. Esquerdo, 44-46

Madrid, 28007, Spain

Location

MD Anderson Cancer Centre, Ctra. Colmenar Viejo Km. 9 100,

Madrid, 28034, Spain

Location

Beatson West of Scotland Cancer Centre, 1053 Great Western Road

Glasgow, G12 0YN, United Kingdom

Location

Leicester General Hospital, Gwndolen Road

Leicester, LE5 4PW, United Kingdom

Location

The Royal Marsden Hospital, Downs Rd, Sutton

London, SM2 5PT, United Kingdom

Location

The Christie Hospital, Wilmslow Road, Withington

Manchester, M20 4BX, United Kingdom

Location

Freeman Hospital, Freeman Road, High Heaton

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Southampton General Hospital, Tremona Road, Shirley

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Escudier B, Faivre S, Van Cutsem E, Germann N, Pouget JC, Plummer R, Vergote I, Thistlethwaite F, Bjarnason GA, Jones R, Mackay H, Edeline J, Fartoux L, Hirte H, Oza A. A Phase II Multicentre, Open-Label, Proof-of-Concept Study of Tasquinimod in Hepatocellular, Ovarian, Renal Cell, and Gastric Cancers. Target Oncol. 2017 Oct;12(5):655-661. doi: 10.1007/s11523-017-0525-2.

  PMID: 28798986 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Ovarian Neoplasms; Carcinoma, Renal Cell; Stomach Neoplasms; Neoplasm Metastasis

Interventions

tasquinimod

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2012
• First Posted: December 6, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: April 1, 2016
• Last Updated: January 8, 2019
• Results First Posted: May 7, 2018

Record last verified: 2019-01

Locations

ES (3); BE (3); CA (4); FR (8); GB (6)