A Study With Tasquinimod Treating Patients With Hepatocellular, Ovarian, Renal Cell and Gastric Cancers
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Hepatocellular Carcinoma Cohort 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
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.
Other Names:
|
| Experimental: Ovarian Carcinoma Cohort 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
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.
Other Names:
|
| Experimental: Renal Cell Carcinoma Cohort 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
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.
Other Names:
|
| Experimental: Gastric Carcinoma Cohort 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
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria - All Patients:
-
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.
- Adequate hepatic function:
-
Serum bilirubin ≤1.5 mg/dL (≤25 μmol/L) for ovarian carcinoma, renal cell carcinoma and gastric carcinoma, serum bilirubin ≤3 mg/dL (≤50 μmol/L) for hepatocellular carcinoma cohorts.
-
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver lesions were present i.e. liver metastasis or primary tumour of the liver for hepatocellular carcinoma cohort).
- Adequate bone marrow function:
-
Absolute neutrophil count (ANC) ≥1.5 x 10^9/L.
-
Platelets ≥50 x 10^9/L.
-
Haemoglobin ≥90 g/L.
-
Adequate coagulation tests: international normalised ratio (INR) ≤1.5 x ULN.
-
Able to swallow capsules.
-
For women of childbearing potential, a negative pregnancy test must have been documented prior to first administration of study treatment.
-
For women who were not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use adequate methods of contraception (e.g. hormonal implants, combined oral contraceptives, vasectomised partner), during the treatment period and for at least 3 months after the last dose of study treatment.
-
For men: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose of study treatment.
Inclusion Criteria - Hepatocellular Carcinoma Cohort:
-
Histologically confirmed and documented hepatocellular carcinoma (excluding fibrolamellar carcinoma).
-
Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to locoregional therapy or refractory to locoregional therapy.
-
Liver mass measuring at least 2 cm with characteristic vascularisation seen on either triphasic computed tomography (CT) scan or Magnetic Resonance Imaging (MRI) with gadolinium.
-
At least one measurable or evaluable lesion that was viable (i.e. vascularised), and had not been previously treated with locoregional therapy. A lesion that had been previously treated qualified as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy.
-
Child-Pugh A Class only.
-
Previously treated with sorafenib. Patients may have experienced radiographically documented disease progression during sorafenib therapy or after discontinuation of sorafenib therapy.
-
The patient had received sorafenib as the most recent systemic therapeutic intervention (any hepatic locoregional therapy that had been administered prior to sorafenib was allowed, but not following sorafenib; radiation to metastatic sites [e.g. bone] following sorafenib therapy was permitted).
Inclusion Criteria - Ovarian Carcinoma Cohort:
-
Histologically confirmed and documented ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer.
-
Progression within 6 months of a platinum containing chemotherapy regimen (i.e. platinum resistant).
-
Progression after up to three lines of chemotherapy.
-
Maximum one line treatment with antiangiogenic therapy.
Inclusion Criteria - Renal Cell Carcinoma Cohort:
-
Metastatic renal cell carcinoma.
-
Histologically or cytologically confirmed and documented renal cell carcinoma with a clear cell component.
-
Previous treatment with at least one vascular endothelial growth factor inhibitor.
-
Disease progression within 6 months prior to first study treatment.
-
Patient had at most two prior targeted therapies for unresectable advanced or metastatic disease.
Inclusion Criteria - Gastric Carcinoma Cohort:
-
Histologically or cytologically confirmed and documented adenocarcinoma of the stomach or gastroesophageal junction.
-
Unresectable advanced or initially metastatic or recurrent after curative resection.
-
Progression after one prior regimen of chemotherapy including fluoropyrimidine and platinum (with or without trastuzumab, if human epidermal growth factor receptor 2 positive [HER2+]).
-
Maximum one line treatment with antiangiogenic therapy.
Exclusion Criteria - All Patients:
-
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.
Exclusion Criteria - Hepatocellular Carcinoma Cohort:
- Fibrolamellar carcinoma.
Exclusion Criteria - Ovarian Carcinoma Cohort:
- Non-epithelial cancer and borderline tumours (e.g. tumours of low malignant potential).
Exclusion Criteria - Gastric Carcinoma Cohort:
- Other histologic type than adenocarcinoma.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Antwerp University Hospital, Wilrijkstraat 10 | Edegem | Belgium | 2650 | |
| 2 | Ghent University Hospital, 1K12 IE, De Pintelaan 185 | Gent | Belgium | 9000 | |
| 3 | Leuven cancer institute (LKI), Herestraat | Leuven | Belgium | 3000 | |
| 4 | Juravinski Cancer Centre, 699 Concession St | Hamilton | Ontario | Canada | L8V 5C2 |
| 5 | London Health Sciences Center, 790 Commissoners Road East | London | Ontario | Canada | N6A 4L6 |
| 6 | Sunnybrook, 2075 Bayview Avenue, Suite T2049 | Toronto | Ontario | Canada | M4N 3M5 |
| 7 | Princess Margaret, 610 University Avenue | Toronto | Ontario | Canada | M5G 2M9 |
| 8 | Hospital Beaujon, 100 Blvd du Général Leclerc | Clichy | France | 92110 | |
| 9 | Centre Oscar Lambret, 3 rue Frédéric Combemale | Lille cedex | France | 59020 | |
| 10 | Bureau d'Etudes Cliniques du Centre Léon Bérard, 28, rue Laennec | Lyon | France | 69008 | |
| 11 | Hospital Saint-Antoine, 184 rue du Faubourg St Antoine | Paris | France | 75012 | |
| 12 | Hopital Europeen Georges-Pompidou, AP-HP, 20 Rue Leblanc | Paris | France | 75015 | |
| 13 | Centre Eugene Marquis, Avenue bataille Flandres Dunkerque | Rennes cedex | France | 35042 | |
| 14 | Centre René Gauducheau, Boulevard Jacques Monod | Saint Herblain | France | 44805 | |
| 15 | Institute Gustave-Roussy, 114 rue Edouard Vaillant | Villejuif | France | 94805 | |
| 16 | Hospital del mar, Paseo Maritimo 25-29 | Barcelona | Spain | 08003 | |
| 17 | Hospital Gregorio Marañon, Dr. Esquerdo, 44-46 | Madrid | Spain | 28007 | |
| 18 | MD Anderson Cancer Centre, Ctra. Colmenar Viejo Km. 9 100, | Madrid | Spain | 28034 | |
| 19 | Beatson West of Scotland Cancer Centre, 1053 Great Western Road | Glasgow | United Kingdom | G12 0YN | |
| 20 | Leicester General Hospital, Gwndolen Road | Leicester | United Kingdom | LE5 4PW | |
| 21 | The Royal Marsden Hospital, Downs Rd, Sutton | London | United Kingdom | SM2 5PT | |
| 22 | The Christie Hospital, Wilmslow Road, Withington | Manchester | United Kingdom | M20 4BX | |
| 23 | Freeman Hospital, Freeman Road, High Heaton | Newcastle-upon-Tyne | United Kingdom | NE7 7DN | |
| 24 | Southampton General Hospital, Tremona Road, Shirley | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Ipsen
Investigators
- Study Director: Ipsen Medical Director, Ipsen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8-55-58102-004
- 2012-002326-75
Study Results
Participant Flow
| Recruitment Details | Patients were recruited from 24 investigational sites in Belgium, Canada, the United Kingdom, Spain and France. The first patient was enrolled in December 2012 and the study was completed in April 2016. |
|---|---|
| Pre-assignment Detail | In the hepatocellular carcinoma cohort 67 patients were screened, of whom 53 were treated with tasquinimod. In the ovarian carcinoma cohort 63 were screened, of whom 55 were treated. In the renal cell carcinoma cohort 44 were screened, of whom 38 were treated. In the gastric carcinoma cohort 27 were screened, of whom 21 were treated. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. Tasquinimod: 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. | 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. Tasquinimod: 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. | 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. Tasquinimod: 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. | 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. Tasquinimod: 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. |
| Period Title: Active Treatment Phase | ||||
| STARTED | 53 | 55 | 38 | 21 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 53 | 55 | 38 | 21 |
| Period Title: Active Treatment Phase | ||||
| STARTED | 51 | 53 | 37 | 21 |
| COMPLETED | 6 | 5 | 14 | 5 |
| NOT COMPLETED | 45 | 48 | 23 | 16 |
Baseline Characteristics
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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. Tasquinimod: 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. | 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. Tasquinimod: 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. | 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. Tasquinimod: 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. | 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. Tasquinimod: 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. | Total of all reporting groups |
| Overall Participants | 53 | 55 | 38 | 21 | 167 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
19
35.8%
|
34
61.8%
|
25
65.8%
|
11
52.4%
|
89
53.3%
|
| >=65 years |
34
64.2%
|
21
38.2%
|
13
34.2%
|
10
47.6%
|
78
46.7%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
8
15.1%
|
55
100%
|
10
26.3%
|
4
19%
|
77
46.1%
|
| Male |
45
84.9%
|
0
0%
|
28
73.7%
|
17
81%
|
90
53.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
1.9%
|
0
0%
|
1
2.6%
|
0
0%
|
2
1.2%
|
| Not Hispanic or Latino |
33
62.3%
|
53
96.4%
|
33
86.8%
|
19
90.5%
|
138
82.6%
|
| Unknown or Not Reported |
19
35.8%
|
2
3.6%
|
4
10.5%
|
2
9.5%
|
27
16.2%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
5.7%
|
2
3.6%
|
0
0%
|
2
9.5%
|
7
4.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
3.8%
|
2
3.6%
|
0
0%
|
0
0%
|
4
2.4%
|
| White |
29
54.7%
|
49
89.1%
|
35
92.1%
|
17
81%
|
130
77.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
19
35.8%
|
2
3.6%
|
3
7.9%
|
2
9.5%
|
26
15.6%
|
| Region of Enrollment (Count of Participants) | |||||
| Canada |
3
5.7%
|
22
40%
|
9
23.7%
|
4
19%
|
38
22.8%
|
| Belgium |
3
5.7%
|
10
18.2%
|
0
0%
|
2
9.5%
|
15
9%
|
| United Kingdom |
3
5.7%
|
11
20%
|
14
36.8%
|
13
61.9%
|
41
24.6%
|
| France |
43
81.1%
|
9
16.4%
|
12
31.6%
|
2
9.5%
|
66
39.5%
|
| Spain |
1
1.9%
|
3
5.5%
|
3
7.9%
|
0
0%
|
7
4.2%
|
Outcome Measures
| Title | 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). |
|---|---|
| Description | 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'. |
| Time Frame | Week 12 (Gastric Carcinoma Cohort); Week 16 (Hepatocellular and Renal Cell Carcinoma Cohorts); Week 24 (Ovarian Carcinoma Cohort). |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: All treated patients i.e. all patients who had received at least one dose of tasquinimod. An additional patient was included in the hepatocellular carcinoma cohort, since the 52nd (last patient planned in the protocol) and 53rd were screened at the same time. This 53rd was not included in the primary analysis. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 52 | 55 | 38 | 21 |
| Number (95% Confidence Interval) [percentage of participants] |
26.9
50.8%
|
7.3
13.3%
|
13.2
34.7%
|
9.5
45.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Hepatocellular Carcinoma Cohort |
|---|---|---|
| Comments | The PFS rate was compared with the prespecified threshold (>20%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.142 |
| Comments | One-sided alpha of 0.1. | |
| Method | Exact binomial test | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Ovarian Carcinoma Cohort |
|---|---|---|
| Comments | The PFS rate was compared with the prespecified threshold (>35%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | One-sided alpha of 0.1. | |
| Method | Exact binomial test | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Renal Cell Carcinoma Cohort |
|---|---|---|
| Comments | The PFS rate was compared with the prespecified threshold (>20%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.800 |
| Comments | One-sided alpha of 0.1 | |
| Method | Exact binomial test | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Gastric Carcinoma Cohort |
|---|---|---|
| Comments | The PFS rate was compared with the prespecified threshold (>15%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.630 |
| Comments | One-sided alpha of 0.1 | |
| Method | Exact binomial test | |
| Comments | ||
| Title | PFS Rate Measured by Choi Criteria (Hepatocellular Carcinoma Cohort). |
|---|---|
| Description | 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. |
| Time Frame | Week 16. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort |
|---|---|
| Arm/Group Description | 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. 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. |
| Measure Participants | 53 |
| Number (95% Confidence Interval) [percentage of participants] |
20.8
39.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Hepatocellular Carcinoma Cohort |
|---|---|---|
| Comments | The PFS rate was compared with a prespecified threshold (>20%). | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.500 |
| Comments | One-sided alpha of 0.1. | |
| Method | Exact binomial test | |
| Comments | ||
| Title | Best Overall Response and Response Rates (All Cohorts) Using RECIST v1.1 (Centrally and Locally Analysed). |
|---|---|
| Description | 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. |
| Time Frame | 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at lease one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 53 | 55 | 38 | 21 |
| Best overall response: PR (centrally assessed) |
1.9
3.6%
|
1.8
3.3%
|
0
0%
|
0
0%
|
| Best overall response: SD (centrally assessed) |
54.7
103.2%
|
49.1
89.3%
|
47.4
124.7%
|
23.8
113.3%
|
| Best overall response: PD (centrally assessed) |
34.0
64.2%
|
41.8
76%
|
44.7
117.6%
|
66.7
317.6%
|
| Best overall response: NE (centrally assessed) |
9.4
17.7%
|
7.3
13.3%
|
7.9
20.8%
|
9.5
45.2%
|
| Response rate (CR or PR) (centrally assessed) |
1.9
3.6%
|
1.8
3.3%
|
0
0%
|
0
0%
|
| Best overall response: PR (locally assessed) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Best overall response: SD (locally assessed) |
52.8
99.6%
|
32.7
59.5%
|
39.5
103.9%
|
14.3
68.1%
|
| Best overall response: PD (locally assessed) |
43.4
81.9%
|
61.8
112.4%
|
57.9
152.4%
|
81.0
385.7%
|
| Best overall response: NE (locally assessed) |
3.8
7.2%
|
5.5
10%
|
2.6
6.8%
|
4.8
22.9%
|
| Response rate (CR or PR) (locally assessed) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Best Overall Response and Response Rate Based on Choi Criteria (Hepatocellular Carcinoma Cohort). |
|---|---|
| Description | 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 Frame | Every 8 weeks until disease progression, up to 36 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort |
|---|---|
| Arm/Group Description | 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. 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. |
| Measure Participants | 53 |
| Best overall response: PR |
20.8
39.2%
|
| Best overall response: SD |
32.1
60.6%
|
| Best overall response: PD |
34.0
64.2%
|
| Best overall response: NE |
13.2
24.9%
|
| Response rate (CR or PR) |
20.8
39.2%
|
| Title | Clinical Benefit (All Cohorts). |
|---|---|
| Description | Clinical benefit was defined as CR, PR or SD lasting at least 12 weeks using centrally or locally assessed RECIST v1.1. |
| Time Frame | 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 53 | 55 | 38 | 21 |
| Clinical benefit (centrally assessed) |
26.4
49.8%
|
20.0
36.4%
|
15.8
41.6%
|
0.0
0%
|
| Clinical benefit (locally assessed) |
32.1
60.6%
|
16.4
29.8%
|
15.8
41.6%
|
0.0
0%
|
| Title | PFS From First Study Treatment to Progression or Death Due to Any Cause Based on Choi Criteria (Hepatocellular Carcinoma Cohort). |
|---|---|
| Description | 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. |
| Time Frame | Every 8 weeks until disease progression, up to 36 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort |
|---|---|
| Arm/Group Description | 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. 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. |
| Measure Participants | 53 |
| Median (95% Confidence Interval) [Weeks] |
15.71
|
| Title | PFS From First Study Treatment to Progression or Death Due to Any Cause Based on RECIST v1.1 Criteria (All Cohorts). |
|---|---|
| Description | 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. |
| Time Frame | 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 53 | 55 | 38 | 21 |
| PFS (centrally assessed) |
15.86
|
8.00
|
14.86
|
6.00
|
| PFS (locally assessed) |
15.71
|
7.57
|
7.86
|
5.79
|
| Title | Time to Progression (TTP) by Choi Criteria (Hepatocellular Carcinoma Cohort). |
|---|---|
| Description | 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. |
| Time Frame | Every 8 weeks until disease progression, up to 36 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort |
|---|---|
| Arm/Group Description | 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. 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. |
| Measure Participants | 53 |
| Median (95% Confidence Interval) [Weeks] |
15.86
|
| Title | TTP by RECIST v1.1 (All Cohorts). |
|---|---|
| Description | 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. |
| Time Frame | 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 53 | 55 | 38 | 21 |
| TTP (centrally assessed) |
15.86
|
8.00
|
14.86
|
6.00
|
| TTP (locally assessed) |
15.71
|
7.57
|
7.86
|
5.79
|
| Title | Overall Survival (OS), Defined as the Time From First Study Treatment to Death Due to Any Cause (All Cohorts). |
|---|---|
| Description | 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. |
| Time Frame | Time from first study treatment to death, up to 36 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 53 | 55 | 38 | 21 |
| Median (95% Confidence Interval) [Weeks] |
29.29
|
NA
|
32.71
|
21.57
|
| Title | Further Cancer-related Treatment During Follow-up Period (All Cohorts). |
|---|---|
| Description | 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. |
| Time Frame | 16 weeks, Last Patient First Treatment + 16 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population: all treated patients i.e. all patients who had received at least one dose of tasquinimod. |
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort |
|---|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. |
| Measure Participants | 53 | 55 | 38 | 21 |
| Count of Participants [Participants] |
16
30.2%
|
35
63.6%
|
18
47.4%
|
8
38.1%
|
Adverse Events
| Time Frame | Treatment emergent adverse events (TEAEs) were collected during the active phase of the study from treatment start date until predefined timepoint T2, over approximately 1 year. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Tumour-related signs and symptoms were reported as TEAEs during the study only if they worsened in severity or increased in frequency. Natural progression/deterioration of the malignancy and disease progression that led to death were recorded as part of the efficacy evaluation. The Safety population comprised all patients who had received at least one dose of tasquinimod. AEs were coded using MedDRA 17.1 for the Hepatocellular Carcinoma cohort and version 16.1 for all other cohorts. | |||||||
| Arm/Group Title | Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort | ||||
| Arm/Group Description | 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. 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. | 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. 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. | 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. 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. | 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. 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. | ||||
All Cause Mortality |
||||||||
| Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 38/53 (71.7%) | 22/55 (40%) | 22/38 (57.9%) | 16/21 (76.2%) | ||||
Serious Adverse Events |
||||||||
| Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/53 (26.4%) | 19/55 (34.5%) | 11/38 (28.9%) | 7/21 (33.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/53 (3.8%) | 2 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Cardiac disorders | ||||||||
| Myocardial infarction | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Cardiac failure | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Nausea | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 2/21 (9.5%) | 2 |
| Vomiting | 1/53 (1.9%) | 1 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 2/21 (9.5%) | 2 |
| Small intestinal obstruction | 0/53 (0%) | 0 | 2/55 (3.6%) | 2 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Oesophageal varices haemorrhage | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Pancreatitis | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Abdominal pain | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Abdominal pain upper | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Diarrhoea | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Intestinal obstruction | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Ascites | 1/53 (1.9%) | 1 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Subileus | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Rectal haemorrhage | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Colitis | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| General disorders | ||||||||
| Asthenia | 2/53 (3.8%) | 2 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Oedema peripheral | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Fatigue | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Non-cardiac chest pain | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Pyrexia | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Disease progression | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Bile duct obstruction | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Hepatobiliary disease | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Infections and infestations | ||||||||
| Cellulitis | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Upper respiratory tract infection | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Peritonitis | 2/53 (3.8%) | 2 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Infectious pleural effusion | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Lung infection | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Pelvic infection | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Pleural infection | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Urinary tract infection | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Lower respiratory tract infection | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Pneumonia | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Oesophageal candidiasis | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Oral candidiasis | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Humerus fracture | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Upper limb fracture | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Investigations | ||||||||
| Blood bilirubin increased | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Blood creatinine increased | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 1/21 (4.8%) | 1 |
| Decreased appetite | 2/53 (3.8%) | 2 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hypercalcaemia | 0/53 (0%) | 0 | 1/55 (1.8%) | 2 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hyperkalaemia | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Iron deficiency | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Flank pain | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Back pain | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Pathological fracture | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Pain in extremity | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Inflammatory myofibroblastic tumour | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Tumour pain | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Metastatic pain | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Nervous system disorders | ||||||||
| Hepatic encephalopathy | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Ataxia | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Dizziness | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Partial seizures | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Renal failure acute | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Renal failure | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Pleural effusion | 0/53 (0%) | 0 | 4/55 (7.3%) | 4 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Cough | 0/53 (0%) | 0 | 1/55 (1.8%) | 2 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Dyspnoea | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Pulmonary embolism | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Haemoptysis | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Pleuritic pain | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Hepatocellular Carcinoma Cohort | Ovarian Carcinoma Cohort | Renal Cell Carcinoma Cohort | Gastric Carcinoma Cohort | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/53 (100%) | 55/55 (100%) | 38/38 (100%) | 21/21 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/53 (3.8%) | 2 | 9/55 (16.4%) | 9 | 3/38 (7.9%) | 3 | 5/21 (23.8%) | 7 |
| Cardiac disorders | ||||||||
| Sinus tachycardia | 0/53 (0%) | 0 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Eye disorders | ||||||||
| Periorbital oedema | 0/53 (0%) | 0 | 4/55 (7.3%) | 4 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 15/53 (28.3%) | 17 | 19/55 (34.5%) | 20 | 8/38 (21.1%) | 8 | 9/21 (42.9%) | 11 |
| Nausea | 21/53 (39.6%) | 28 | 24/55 (43.6%) | 30 | 12/38 (31.6%) | 13 | 13/21 (61.9%) | 17 |
| Vomiting | 18/53 (34%) | 25 | 16/55 (29.1%) | 21 | 9/38 (23.7%) | 9 | 13/21 (61.9%) | 18 |
| Constipation | 15/53 (28.3%) | 16 | 12/55 (21.8%) | 12 | 13/38 (34.2%) | 13 | 11/21 (52.4%) | 13 |
| Gastrooesophageal reflux disease | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 1/38 (2.6%) | 2 | 5/21 (23.8%) | 6 |
| Dyspepsia | 0/53 (0%) | 0 | 5/55 (9.1%) | 6 | 2/38 (5.3%) | 2 | 4/21 (19%) | 4 |
| Diarrhoea | 14/53 (26.4%) | 20 | 14/55 (25.5%) | 18 | 7/38 (18.4%) | 8 | 3/21 (14.3%) | 3 |
| Abdominal distension | 4/53 (7.5%) | 4 | 10/55 (18.2%) | 12 | 1/38 (2.6%) | 1 | 2/21 (9.5%) | 2 |
| Abdominal pain upper | 7/53 (13.2%) | 9 | 13/55 (23.6%) | 14 | 1/38 (2.6%) | 1 | 2/21 (9.5%) | 2 |
| Epigastric discomfort | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 2/21 (9.5%) | 2 |
| Eructation | 0/53 (0%) | 0 | 1/55 (1.8%) | 1 | 0/38 (0%) | 0 | 2/21 (9.5%) | 2 |
| Retching | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 2/21 (9.5%) | 4 |
| Ascites | 5/53 (9.4%) | 8 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Dysphagia | 3/53 (5.7%) | 4 | 1/55 (1.8%) | 1 | 1/38 (2.6%) | 2 | 1/21 (4.8%) | 1 |
| Dry mouth | 2/53 (3.8%) | 2 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| General disorders | ||||||||
| Oedema peripheral | 16/53 (30.2%) | 18 | 17/55 (30.9%) | 21 | 4/38 (10.5%) | 9 | 2/21 (9.5%) | 2 |
| Fatigue | 31/53 (58.5%) | 36 | 31/55 (56.4%) | 41 | 7/38 (18.4%) | 7 | 15/21 (71.4%) | 18 |
| Asthenia | 7/53 (13.2%) | 8 | 5/55 (9.1%) | 7 | 11/38 (28.9%) | 17 | 0/21 (0%) | 0 |
| Pyrexia | 2/53 (3.8%) | 4 | 8/55 (14.5%) | 10 | 1/38 (2.6%) | 1 | 1/21 (4.8%) | 1 |
| Chest pain | 1/53 (1.9%) | 1 | 0/55 (0%) | 0 | 2/38 (5.3%) | 2 | 0/21 (0%) | 0 |
| Chills | 0/53 (0%) | 0 | 2/55 (3.6%) | 2 | 2/38 (5.3%) | 2 | 1/21 (4.8%) | 1 |
| Influenza like illness | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 2/38 (5.3%) | 2 | 0/21 (0%) | 0 |
| Infections and infestations | ||||||||
| Lower respiratory tract infection | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 5/38 (13.2%) | 6 | 3/21 (14.3%) | 3 |
| Oral candidiasis | 1/53 (1.9%) | 1 | 2/55 (3.6%) | 2 | 0/38 (0%) | 0 | 3/21 (14.3%) | 4 |
| Urinary tract infection | 1/53 (1.9%) | 1 | 7/55 (12.7%) | 7 | 0/38 (0%) | 0 | 2/21 (9.5%) | 3 |
| Rash pustular | 4/53 (7.5%) | 4 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Bronchitis | 3/53 (5.7%) | 3 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 0/53 (0%) | 0 | 4/55 (7.3%) | 5 | 0/38 (0%) | 0 | 3/21 (14.3%) | 4 |
| Investigations | ||||||||
| Weight decreased | 13/53 (24.5%) | 14 | 3/55 (5.5%) | 3 | 5/38 (13.2%) | 5 | 6/21 (28.6%) | 6 |
| Blood alkaline phosphatase increased | 1/53 (1.9%) | 1 | 4/55 (7.3%) | 4 | 1/38 (2.6%) | 1 | 3/21 (14.3%) | 3 |
| Alanine aminotransferase increased | 3/53 (5.7%) | 3 | 6/55 (10.9%) | 7 | 0/38 (0%) | 0 | 2/21 (9.5%) | 3 |
| Aspartate aminotransferase increased | 4/53 (7.5%) | 4 | 6/55 (10.9%) | 7 | 1/38 (2.6%) | 1 | 2/21 (9.5%) | 2 |
| Blood lactate dehydrogenase increased | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 2/21 (9.5%) | 2 |
| Blood bilirubin increased | 4/53 (7.5%) | 4 | 2/55 (3.6%) | 2 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Gamma-glutamyltransferase increased | 1/53 (1.9%) | 1 | 5/55 (9.1%) | 5 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Lipase increased | 0/53 (0%) | 0 | 6/55 (10.9%) | 6 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Amylase increased | 0/53 (0%) | 0 | 5/55 (9.1%) | 5 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 21/53 (39.6%) | 22 | 20/55 (36.4%) | 25 | 11/38 (28.9%) | 11 | 15/21 (71.4%) | 17 |
| Hyponatraemia | 1/53 (1.9%) | 2 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hypercalcaemia | 0/53 (0%) | 0 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hypokalaemia | 1/53 (1.9%) | 1 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hypoalbuminaemia | 2/53 (3.8%) | 3 | 6/55 (10.9%) | 6 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hyperglycaemia | 0/53 (0%) | 0 | 4/55 (7.3%) | 5 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hypomagnesaemia | 0/53 (0%) | 0 | 4/55 (7.3%) | 4 | 0/38 (0%) | 0 | 1/21 (4.8%) | 1 |
| Glucose tolerance impaired | 0/53 (0%) | 0 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 9/53 (17%) | 11 | 14/55 (25.5%) | 15 | 5/38 (13.2%) | 6 | 11/21 (52.4%) | 12 |
| Pain in extremity | 4/53 (7.5%) | 6 | 5/55 (9.1%) | 6 | 4/38 (10.5%) | 6 | 4/21 (19%) | 5 |
| Flank pain | 2/53 (3.8%) | 3 | 2/55 (3.6%) | 2 | 1/38 (2.6%) | 1 | 2/21 (9.5%) | 2 |
| Arthralgia | 5/53 (9.4%) | 8 | 10/55 (18.2%) | 11 | 2/38 (5.3%) | 3 | 3/21 (14.3%) | 5 |
| Musculoskeletal pain | 3/53 (5.7%) | 4 | 4/55 (7.3%) | 5 | 4/38 (10.5%) | 6 | 2/21 (9.5%) | 2 |
| Myalgia | 2/53 (3.8%) | 3 | 6/55 (10.9%) | 6 | 4/38 (10.5%) | 4 | 2/21 (9.5%) | 2 |
| Bone pain | 4/53 (7.5%) | 4 | 2/55 (3.6%) | 2 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Neck pain | 3/53 (5.7%) | 3 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Muscular weakness | 1/53 (1.9%) | 1 | 3/55 (5.5%) | 3 | 1/38 (2.6%) | 1 | 0/21 (0%) | 0 |
| Nervous system disorders | ||||||||
| Headache | 9/53 (17%) | 9 | 10/55 (18.2%) | 13 | 4/38 (10.5%) | 4 | 1/21 (4.8%) | 1 |
| Peripheral sensory neuropathy | 4/53 (7.5%) | 4 | 2/55 (3.6%) | 2 | 2/38 (5.3%) | 2 | 1/21 (4.8%) | 1 |
| Dizziness | 2/53 (3.8%) | 2 | 5/55 (9.1%) | 5 | 4/38 (10.5%) | 5 | 1/21 (4.8%) | 1 |
| Amnesia | 0/53 (0%) | 0 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Lethargy | 0/53 (0%) | 0 | 2/55 (3.6%) | 2 | 5/38 (13.2%) | 5 | 1/21 (4.8%) | 1 |
| Dysgeusia | 1/53 (1.9%) | 1 | 1/55 (1.8%) | 1 | 2/38 (5.3%) | 2 | 0/21 (0%) | 0 |
| Neuralgia | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 2/38 (5.3%) | 2 | 0/21 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Insomnia | 9/53 (17%) | 11 | 9/55 (16.4%) | 10 | 6/38 (15.8%) | 6 | 6/21 (28.6%) | 6 |
| Reproductive system and breast disorders | ||||||||
| Pelvic pain | 1/53 (1.9%) | 1 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 5/53 (9.4%) | 5 | 12/55 (21.8%) | 12 | 9/38 (23.7%) | 10 | 3/21 (14.3%) | 3 |
| Dyspnoea | 10/53 (18.9%) | 12 | 12/55 (21.8%) | 13 | 3/38 (7.9%) | 3 | 1/21 (4.8%) | 1 |
| Pleural effusion | 1/53 (1.9%) | 1 | 2/55 (3.6%) | 2 | 2/38 (5.3%) | 2 | 0/21 (0%) | 0 |
| Dyspnoea exertional | 0/53 (0%) | 0 | 3/55 (5.5%) | 3 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Dry skin | 3/53 (5.7%) | 3 | 1/55 (1.8%) | 1 | 3/38 (7.9%) | 3 | 1/21 (4.8%) | 1 |
| Pruritus | 2/53 (3.8%) | 2 | 4/55 (7.3%) | 4 | 3/38 (7.9%) | 4 | 0/21 (0%) | 0 |
| Rash | 0/53 (0%) | 0 | 4/55 (7.3%) | 5 | 3/38 (7.9%) | 3 | 0/21 (0%) | 0 |
| Hyperhidrosis | 0/53 (0%) | 0 | 3/55 (5.5%) | 3 | 3/38 (7.9%) | 3 | 1/21 (4.8%) | 1 |
| Palmar-plantar erythrodysaesthesia syndrome | 0/53 (0%) | 0 | 2/55 (3.6%) | 2 | 3/38 (7.9%) | 3 | 0/21 (0%) | 0 |
| Night sweats | 1/53 (1.9%) | 1 | 2/55 (3.6%) | 2 | 2/38 (5.3%) | 2 | 1/21 (4.8%) | 1 |
| Vascular disorders | ||||||||
| Orthostatic hypotension | 0/53 (0%) | 0 | 0/55 (0%) | 0 | 1/38 (2.6%) | 1 | 2/21 (9.5%) | 2 |
| Hypertension | 3/53 (5.7%) | 4 | 0/55 (0%) | 0 | 0/38 (0%) | 0 | 0/21 (0%) | 0 |
| Hypotension | 1/53 (1.9%) | 1 | 1/55 (1.8%) | 1 | 5/38 (13.2%) | 5 | 1/21 (4.8%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor required reasonable opportunity to review any abstract, presentation, or paper before the material was submitted for publication or communicated. This also applied to any amendments that were requested by referees or journal editors. The Sponsor committed to comment on the draft documents within a time period agreed in the contractual arrangements between the Sponsor and authors or their institution. Delays were also possible if publication would adversely affect patentability.
Results Point of Contact
| Name/Title | Medical Director, Oncology |
|---|---|
| Organization | Ipsen |
| Phone | clinical.trials@ipsen.com |
| clinical.trials@ipsen.com |
- 8-55-58102-004
- 2012-002326-75