Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to ReceivePhase 2TR1USNCT02066675
Trabectedin First Line Therapy In Unfit Sarcoma Study
A Phase 2 study testing Trabectedin in people with Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive and Standard Chemotherapy, run by Italian Sarcoma Group at 16 sites in Italy.
Trial summary
Phase II, non-randomized, two-stage study according to Bryant \& Day The study enroll patients with Metastatic and locally advanced soft tissue sarcoma unfit to receive standard chemotherapy (doxorubicin/epirubicin and/or ifosfamide) Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive, Standard Chemotherapy
- What is being tested?
- Trabectedin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 16 sitesItaly
- Study dates
- Feb 2014to 31 Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (≥18 years), who, in the judgment of the clinician, is deemed not suitable to receive an anthracycline and/or ifosfamide based chemotherapy;
- Pathological diagnosis of soft tissue sarcoma
- Inoperable, locally advanced or metastatic tumor;
- Unsuited to receive doxorubicine and ifosfamide: ie stable arrhythmia, previous myocardial infarction; age≥80 years
- Eastern Cooperative Oncology Group Performance Status 0-2
- Glomerular filtration rate ≥30 mL per min
Show all 10Show fewer
- Adequate hematologic function: Hemoglobin ≥9 g/dL; Absolute neutrophil count ≥1,500/μL, and Platelet count ≥100,000/microliter
- Creatinine phosphokinase < 2.5 Upper Normal Limit
- Adequate hepatic function: total bilirubin < Upper Normal Limit, total alkaline phosphatase < 2.5 Upper Normal Limit, or if > 2.5 Upper Normal Limit consider alkaline phosphatase liver fraction or gamma-glutamyltransferase or 5' nucleotidase must be < Transminase <2.5 x Upper Normal Limit, Albumin > 20 g/L.
- Patient´s written informed consent
Who cannot join
- Prior exposure to Trabectedin
- Performance status ≥2.
- Prior treatment with anthracyclines and or ifosfamide.
- History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission for 5 or more years and judged of negligible potential of relapse.
- Active viral hepatitis or chronic liver diseases, which in the judgement of the primary investigator represents a clinical contraindication to the therapy.
- Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within 6 months before enrolment, uncontrolled arterial hypertension or arrhythmias, left ventricular ejection fraction <40%
Show all 9Show fewer
- Active major infection.
- Other serious concomitant illnesses
- Pregnant subjects or breast feeding, or planning to become pregnant within 6 months after the end of treatment All sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrollment and must agree to use highly effective contraception during treatment and for 6 months after the end of treatment.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Italy16 sites
A.S.O. "SS Antonio e Biagio e Cesare Arrigo"
Alessandria
Ospedali Riuniti di Bergamo
Bergamo, BG
Istituti Ortopedici Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors
Bologna, 40136
I.R.C.C. - Unit of Medical Oncology
Candiolo, Torino, 10060
Ospedale SS. Trinità di Sora
Frosinone
Ospedale Galliera
Genova, Genovs
IRCCS Azienda Ospedaliera Universitaria San Martino IST
Genova, GE
Ospedale Villa Scassi
Genova, GE
IST
Genova
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST
Meldola, FC
Policlinico Federico II Napoli
Naples
Istituto Oncologico Veneto
Padova
Ospedale Giaccone
Palermo
Ospedale Misericordia e Dolce" Istituto Toscano Tumori, Azienda USL4
Prato, PO
Campus Biomedico
Roma
Presidio Sanitario Gradenigo
Torino, TO, 10153
About this study
Official title: SAFETY AND ACTIVITY OF TRABECTEDIN AS FIRST LINE IN ADVANCED SOFT TISSUE SARCOMA (STS) PATIENTS UNFIT TO RECEIVE STANDARD CHEMOTHERAPY: A PROSPECTIVE PHASE II STUDY WITH CLINICAL AND MOLECULAR CORRELATES
Phase II, non-randomized, two-stage study according to Bryant \& Day The study enroll patients with Metastatic and locally advanced soft tissue sarcoma unfit to receive standard chemotherapy (doxorubicin/epirubicin and/or ifosfamide)
Read the detailed description
Soft tissue sarcomas are a group of rare and aggressive disease, comprising more than a hundred different histological subtypes and mainly originating from the embryonic mesoderm. Today, they represent less than 1% of all adult cancers, with an incidence of 3/100000/year and a median age at diagnosis of 65 years. Despite the progress done in the last decade, approximately 50% of STS patients still develop distant metastases within 3 years from the diagnosis and die from their disease. Doxorubicin (or epirubicin) and ifosfamide have been proved to be active in the treatment of STS and they are widely used, alone or in combination, as a first line therapy for locally advanced and metastatic patients. However, the response rate to the combination regimen in non-pretreated patients does not exceed 30-40%, and large randomized clinical trials failed to demonstrate any advantage in survival for the combination compared to single-agent treatment. Trabectedin (Yondelis®) is a marine-derived anticancer agent that has been approved in the European Union as a single agent for the treatment of STS patients after failure of standard chemotherapy (doxorubicin and/or ifosfamide) or for those unsuited to receive these agents. Even if the response rate in soft tissue sarcoma does not exceed 10%, trabectedin can provide a significant clinical benefit, by arresting disease progression in almost 50% of treated patients, with a progression-free survival rate of 20% at 6 months. Trabectedin was found to be particularly active in the treatment of myxoid liposarcoma and uterine leiomyosarcoma, for which better results have been obtained in terms of response rate and survival, suggesting an histotype driven activity. The toxicity profile of trabectedin given as second line therapy has been widely assessed in clinical studies and was largely manageable, with the majority of adverse events being grade 1 or 2 toxicities, generally reversible, dose or time dependent and noncumulative. The good tolerability profile observed in the trials seems to be confirmed also in everyday clinical practice. Conversely, few data are available at the moment about tolerability profile for those patients treated with trabectedin as first line because of medical conditions contraindicating the use of standard agents. The aim of this phase II study is to assess and describe trabectedin toxicity profile in this subset of negatively selected advanced inoperable STS patients.
- Conditions
- Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive, Standard Chemotherapy
- Being tested
- Trabectedin
- Keywords
- Metastatic, Locally advanced, Soft tissue tumors
- Medical subject headings
- Neoplasm Metastasis, Soft Tissue Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrabectedinDrug
Also called Yondelis
Each patients will receive intravenous trabectedin (1.5 mg/mq-1.3 mg/mq) over 24 hours every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Trabectedin | Experimental | Trabectedin administered at the dose of 1.5 mg/mq-1.3 mg/mq a 24-hour continuous infusion via a central venous access, every 3 weeks Receives: Drug: Trabectedin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival Rate
The primary end point of this trial is the Progression Free Survival Rate at 3 months Non progression, is defined as Complete Response, Partial Response or Stable Disease according to Response Evaluation Criteria In Solid Tumours v.1.1 criteria.
Measured: 3 Months
Secondary outcomes (4)
Tolerability and intolerable adverse reaction rate.
Intolerable toxicity is defined as every Adverse Events leading to treatment discontinuation or dose-reduction; furthermore, any Adverse Events of at least grade 3 not resolved within 3 weeks of appropriate management should be regarded as an intolerable toxicity event. For haematological toxicity, given that the use of growth factors will be allowed, an intolerable toxicity is defined either as any grade 4 event, or a grade 3 event not resolved with adequate treatment.
Measured: Day21
Objective response rate
Proportion of patients whose best response is either partial response or complete response
Measured: 5 years
Progression free survival
It's the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not progress
Measured: Average of 5 Months
Overall survival
it's the length of time after the treatment's end that the patient survives
Measured: 18 Months (average)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to ReceiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Italian Sarcoma Group
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Federica Grosso, MD, Principal investigator, ASO SS Antonio e Biagio e C Arrigo Alessandria, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02066675
- Sponsor's protocol ID
- ISG TR1US
- Other IDs
- 2013-001467-23
- Acronym
- TR1US
- Status last verified
- Apr 2018
- First submitted
- 13 Feb 2014
- Last updated
- 11 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fayette J, Coquard IR, Alberti L, Boyle H, Meeus P, Decouvelaere AV, Thiesse P, Sunyach MP, Ranchere D, Blay JY. ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol. 2006 Jul;18(4):347-53. doi: 10.1097/01.cco.0000228740.70379.3f.
PubMed 16721129
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SAFETY AND ACTIVITY OF TRABECTEDIN AS FIRST LINE IN ADVANCED SOFT TISSUE SARCOMA (STS) PATIENTS UNFIT TO RECEIVE STANDARD CHEMOTHERAPY: A PROSPECTIVE PHASE II STUDY WITH CLINICAL AND MOLECULAR CORRELATES
- ClinicalTrials.gov ID
- NCT02066675
- Acronym / sponsor ID
- TR1US / ISG TR1US
- Conditions
- Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive, Standard Chemotherapy
- Keywords
- Metastatic, Locally advanced, Soft tissue tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Italian Sarcoma GroupResearch network
- Study start
- Feb 2014
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase II, non-randomized, two-stage study according to Bryant \& Day The study enroll patients with Metastatic and locally advanced soft tissue sarcoma unfit to receive standard chemotherapy (doxorubicin/epirubicin and/or ifosfamide)
Detailed description
Soft tissue sarcomas are a group of rare and aggressive disease, comprising more than a hundred different histological subtypes and mainly originating from the embryonic mesoderm. Today, they represent less than 1% of all adult cancers, with an incidence of 3/100000/year and a median age at diagnosis of 65 years. Despite the progress done in the last decade, approximately 50% of STS patients still develop distant metastases within 3 years from the diagnosis and die from their disease. Doxorubicin (or epirubicin) and ifosfamide have been proved to be active in the treatment of STS and they are widely used, alone or in combination, as a first line therapy for locally advanced and metastatic patients. However, the response rate to the combination regimen in non-pretreated patients does not exceed 30-40%, and large randomized clinical trials failed to demonstrate any advantage in survival for the combination compared to single-agent treatment. Trabectedin (Yondelis®) is a marine-derived anticancer agent that has been approved in the European Union as a single agent for the treatment of STS patients after failure of standard chemotherapy (doxorubicin and/or ifosfamide) or for those unsuited to receive these agents. Even if the response rate in soft tissue sarcoma does not exceed 10%, trabectedin can provide a significant clinical benefit, by arresting disease progression in almost 50% of treated patients, with a progression-free survival rate of 20% at 6 months. Trabectedin was found to be particularly active in the treatment of myxoid liposarcoma and uterine leiomyosarcoma, for which better results have been obtained in terms of response rate and survival, suggesting an histotype driven activity. The toxicity profile of trabectedin given as second line therapy has been widely assessed in clinical studies and was largely manageable, with the majority of adverse events being grade 1 or 2 toxicities, generally reversible, dose or time dependent and noncumulative. The good tolerability profile observed in the trials seems to be confirmed also in everyday clinical practice. Conversely, few data are available at the moment about tolerability profile for those patients treated with trabectedin as first line because of medical conditions contraindicating the use of standard agents. The aim of this phase II study is to assess and describe trabectedin toxicity profile in this subset of negatively selected advanced inoperable STS patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trabectedin | Experimental | Drug: TrabectedinTrabectedin administered at the dose of 1.5 mg/mq-1.3 mg/mq a 24-hour continuous infusion via a central venous access, every 3 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Adult patients (≥18 years), who, in the judgment of the clinician, is deemed not suitable to receive an anthracycline and/or ifosfamide based chemotherapy;
- Pathological diagnosis of soft tissue sarcoma
- Inoperable, locally advanced or metastatic tumor;
- Unsuited to receive doxorubicine and ifosfamide: ie stable arrhythmia, previous myocardial infarction; age≥80 years
- Eastern Cooperative Oncology Group Performance Status 0-2
Key exclusion criteria (9 listed)
- Prior exposure to Trabectedin
- Performance status ≥2.
- Prior treatment with anthracyclines and or ifosfamide.
- History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission for 5 or more years and judged of negligible potential of relapse.
- Active viral hepatitis or chronic liver diseases, which in the judgement of the primary investigator represents a clinical contraindication to the therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrabectedinAlso: YondelisEach patients will receive intravenous trabectedin (1.5 mg/mq-1.3 mg/mq) over 24 hours every 3 weeks | Drug | Trabectedin |
Primary outcome
Progression Free Survival Rate
Time frame: 3 Months
The primary end point of this trial is the Progression Free Survival Rate at 3 months Non progression, is defined as Complete Response, Partial Response or Stable Disease according to Response Evaluation Criteria In Solid Tumours v.1.1 criteria.
4 secondary outcomes
Tolerability and intolerable adverse reaction rate.
Time frame: Day21
Objective response rate
Time frame: 5 years
Progression free survival
Time frame: Average of 5 Months
Overall survival
Time frame: 18 Months (average)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2018.
- Background: PubMed 16721129Fayette J, Coquard IR, Alberti L, Boyle H, Meeus P, Decouvelaere AV, Thiesse P, Sunyach MP, Ranchere D, Blay JY. ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol. 2006 Jul;18(4):347-53. doi: 10.1097/01.cco.0000228740.70379.3f.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Federica Grosso, MD principal investigator
ASO SS Antonio e Biagio e C Arrigo Alessandria, Italy
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trabectedin in people with Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive and Standard Chemotherapy, run by Italian Sarcoma Group at 16 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival Rate (time frame: 3 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02066675, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2018.