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

Phase 2

Completed

Conditions: Advanced or Metastatic Hepatocellular Cancer
Advanced or Metastatic Ovarian Cancer
Metastatic Renal Cell Cancer
Advanced or Metastatic Gastric Carcinoma

Interventions: Drug: Tasquinimod

Registration Number: NCT01743469

Lead Sponsor: Ipsen

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.

Detailed Description: This was an early stopping design, Phase II, open label, exploratory proof of concept study to evaluate the activity of tasquinimod in four independent cohorts of patients with different tumour types (patients with hepatocellular, ovarian, renal cell or gastric carcinoma, each with progressive disease after standard therapies). Patients initially received 0.5 mg/day tasquinimod dose, increasing to 1 mg/day after at least 2 weeks, unless there were any individual patient safety and tolerability concerns. The treatment period continued until patient disease progression, lost to follow-up, withdrawal or death. During the treatment period, initial study visits were at Week 2, 4 and 8 (± 2 days) for the hepatocellular carcinoma, the ovarian carcinoma and the renal cell carcinoma cohorts and at Week 2, 4 and 6 (± 2 days) for the gastric carcinoma cohort, to allow careful safety monitoring and to facilitate the identification of the individually tolerated dose. After Week 8, when most patients should have reached their tolerable dose, visit frequency was decreased as follows: at Week 16 and 24 (± 2 days) for the hepatocellular carcinoma, the ovarian carcinoma and the renal cell carcinoma cohorts; and at Week 12, 18 and 24 (± 2 days) for the gastric carcinoma cohort. Thereafter visits were once every 8 weeks (± 2 days) for all cohorts. An end of study treatment/withdrawal (EoST/WD) Visit was to be performed at least 14 days after the last dose of study treatment, and/or before treatment with any alternative antitumour therapy was started. Patients who stopped study treatment before disease progression were to be followed up with tumour imaging every 8 weeks until disease progression. Each patient was subsequently followed up for survival (by visit or telephone call) every 3 months after the EoST/WD Visit until death, lost to follow-up, or withdrawal of consent, or until all surviving patients had been followed-up for at least 9 months after their last administration of study treatment.

The clinical activity of tasquinimod was evaluated independently in each cohort of patients of the four different tumour types. Data were presented as of the following study cut-off dates:

* Hepatocellular carcinoma cohort: 03 December 2014 (efficacy data); 11 April 2016 (safety data).

* Ovarian carcinoma cohort: 27 November 2013 (efficacy data); 05 October 2015 (safety data).

* Renal cell carcinoma cohort: 04 December 2013.

* Gastric carcinoma cohort: 27 September 2013.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 201

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gastric Carcinoma Cohort	Tasquinimod	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.
Hepatocellular Carcinoma Cohort	Tasquinimod	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.
Ovarian Carcinoma Cohort	Tasquinimod	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.
Renal Cell Carcinoma Cohort	Tasquinimod	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 was derived as the best overall response documented before the prespecified timepoint (gastric carcinoma cohort: 12 weeks; Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Best Overall Response and Response Rate Based on Choi Criteria (Hepatocellular Carcinoma Cohort).	Every 8 weeks until disease progression, up to 36 months.	Per Choi Criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=10% decrease in the sum of the longest diameter of target lesions; Progression, as a 10% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time to Progression (TTP) by Choi Criteria (Hepatocellular Carcinoma Cohort).	Every 8 weeks until disease progression, up to 36 months.	TTP defined as the time from first study treatment to the first occurrence of disease progression defined according to centrally assessed Choi criteria (i.e. increase in tumor size ≥10%) or death due to disease progression before initiation of a new systemic treatment.
PFS Rate Measured by Choi Criteria (Hepatocellular Carcinoma Cohort).	Week 16.	PFS rate was defined as the percentage of patients who had neither progressed nor died. Tumour progression was assessed centrally using the Choi criteria. Response was measured using the following criteria: CR: Disappearance of all lesions, no new lesions; PR: A decrease in size ≥10% or a decrease in tumour attenuation (Hounsfield unit \[HU\]) ≥15% on CT, no new lesions, no obvious progression of non-measurable disease; SD: Does not meet criteria for CR, PR, or progressive disease (PD), no symptomatic deterioration attributed to tumour progression; PD: An increase in tumour size ≥10% and does not meet criteria of PR by tumour attenuation on CT, new lesions.
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).	Clinical benefit was defined as CR, PR or SD lasting at least 12 weeks using centrally or locally assessed RECIST v1.1.
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.	PFS defined as the time from first study treatment to the first occurrence of a disease progression according to centrally assessed Choi criteria (i.e. increase in tumor size ≥10%) or death due to any cause before initiation of new systemic treatment.
PFS From First Study Treatment to Progression or Death Due to Any Cause Based on RECIST v1.1 Criteria (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 defined as the time from first study treatment to the first occurrence of a disease progression according to centrally and locally assessed RECIST v1.1 (i.e. increase in tumor size ≥20%) or death due to any cause before initiation of new systemic treatment.
TTP by RECIST v1.1 (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).	TTP was defined as the time from first study treatment to the first occurrence of disease progression defined according to centrally and locally assessed RECIST v1.1 criteria (i.e. increase in tumor size ≥20%) or death due to disease progression before initiation of a new systemic treatment.
Further Cancer-related Treatment During Follow-up Period (All Cohorts).	16 weeks, Last Patient First Treatment + 16 weeks.	Further systemic treatment was coded using World Health Organization (WHO) Drug Dictionary (versions: June 2014 for the hepatocellular carcinoma cohort and June 2013 for the ovarian, renal cell and gastric carcinoma cohorts). A frequency table of the number and percentage of patients was provided by Anatomical Therapeutic Chemical (ATC) decode and preferred name.
Overall Survival (OS), Defined as the Time From First Study Treatment to Death Due to Any Cause (All Cohorts).	Time from first study treatment to death, up to 36 months.	OS is the time (in weeks) from the first study medication date to death due to any cause. Patients were censored at the date of last contact (the latest between the time of EoST/WD assessment and follow-up visits). OS was estimated using Kaplan-Meier analysis.

Trial Locations

Locations (24): Leuven cancer institute (LKI), Herestraat
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Leuven, Belgium
Antwerp University Hospital, Wilrijkstraat 10
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Edegem, Belgium
Juravinski Cancer Centre, 699 Concession St
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Hamilton, Ontario, Canada
Sunnybrook, 2075 Bayview Avenue, Suite T2049
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Toronto, Ontario, Canada
London Health Sciences Center, 790 Commissoners Road East
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London, Ontario, Canada
Centre Oscar Lambret, 3 rue Frédéric Combemale
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Lille cedex, France
Bureau d'Etudes Cliniques du Centre Léon Bérard, 28, rue Laennec
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Lyon, France
Hospital Saint-Antoine, 184 rue du Faubourg St Antoine
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Paris, France
Hopital Europeen Georges-Pompidou, AP-HP, 20 Rue Leblanc
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Paris, France
Centre Eugene Marquis, Avenue bataille Flandres Dunkerque
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Rennes cedex, France
Centre René Gauducheau, Boulevard Jacques Monod
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Saint Herblain, France
Institute Gustave-Roussy, 114 rue Edouard Vaillant
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Villejuif, France
Hospital del mar, Paseo Maritimo 25-29
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Barcelona, Spain
MD Anderson Cancer Centre, Ctra. Colmenar Viejo Km. 9 100,
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Madrid, Spain
Hospital Gregorio Marañon, Dr. Esquerdo, 44-46
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Madrid, Spain
Beatson West of Scotland Cancer Centre, 1053 Great Western Road
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Glasgow, United Kingdom
Leicester General Hospital, Gwndolen Road
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Leicester, United Kingdom
The Royal Marsden Hospital, Downs Rd, Sutton
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London, United Kingdom
The Christie Hospital, Wilmslow Road, Withington
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Manchester, United Kingdom
Freeman Hospital, Freeman Road, High Heaton
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Newcastle-upon-Tyne, United Kingdom
Southampton General Hospital, Tremona Road, Shirley
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Southampton, United Kingdom
Ghent University Hospital, 1K12 IE, De Pintelaan 185
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Gent, Belgium
Princess Margaret, 610 University Avenue
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Toronto, Ontario, Canada
Hospital Beaujon, 100 Blvd du Général Leclerc
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Clichy, France