T-DIS: Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma

Sponsor

Centre Oscar Lambret (Other)

Overall Status

Completed

CT.gov ID

NCT01303094

Collaborator

French Sarcoma Group (Other), Study Group of Bone Tumors (Other)

Enrollment

Locations

Arms

90.2

Actual Duration (Months)

3.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomization discontinuation trial will allow for concomitant evaluation of the following:

Side effects and benefits of immediate continuation of Trabectedin after the sixth cycle
Side effects and benefits of a drug holiday

Condition or Disease	Intervention/Treatment	Phase
Soft Tissue Sarcoma Uterine Sarcoma	Drug: Trabectedin Other: Drug: holiday	Phase 2

Detailed Description

Selection part (220 patients):

Trabectedin (depending on dose reductions : between 1.5 and 1 mg/m²/3 weeks; over 24 hour administration) until progression, intolerance or 6 cycles (according to the SPC of Trabectedin)

Randomized part (50 patients):

After the 6 first cycles, if there is not progression or unacceptable toxicity, the patients will be randomly assigned to continuous or "intermittent/holiday" therapy with CT-scan evaluation every 6 weeks in both arms

Arm A Continuation of Trabectedin (between 1.5 and 1 mg/m²/3 weeks; over 24 hour administration) until progression or intolerance
Arm B "Intermittent/holiday" therapy. Rechallenge of Trabectedin will be implemented in the event of progression; in this case administration of Trabectedin will occur until the second progression or intolerance

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Randomized Trial to Evaluate Two Strategies: Continuing Versus Intermittent (Drug-holiday) Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the Sixth Cycle

Actual Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

May 16, 2018

Actual Study Completion Date :

Aug 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Continuation of Trabectedin patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle, every 3 weeks until progression/ toxicity	Drug: Trabectedin Trabectedin will be administered without drug holiday in Arm A until unacceptable toxicity, progressive disease or patient decision. The treatment beyond disease progression and in case of intolerance will be decided according to investigator discretion. In case of progression after drug discontinuation by patient decision, a re-challenge of Trabectedin is possible. Other Names: Yondelis
Other: "Drug holiday" therapy patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle and he stops the drug until progression and re-challenge	Other: Drug: holiday A drug-holiday will start after the 6th cycle until disease progression, and then Trabectedin will be re-challenged. Trabectedin will be administered until unacceptable toxicity, second evidence of progressive disease or patient decision. Other Names: No drug

Arm

Intervention/Treatment

Other: Continuation of Trabectedin

patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle, every 3 weeks until progression/ toxicity

Drug: Trabectedin

Trabectedin will be administered without drug holiday in Arm A until unacceptable toxicity, progressive disease or patient decision. The treatment beyond disease progression and in case of intolerance will be decided according to investigator discretion. In case of progression after drug discontinuation by patient decision, a re-challenge of Trabectedin is possible.

Other Names:

Yondelis

Other: "Drug holiday" therapy

patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle and he stops the drug until progression and re-challenge

Other: Drug: holiday

A drug-holiday will start after the 6th cycle until disease progression, and then Trabectedin will be re-challenged. Trabectedin will be administered until unacceptable toxicity, second evidence of progressive disease or patient decision.

Other Names:

No drug

Outcome Measures

Primary Outcome Measures

PFS rate 24 weeks after randomization [24 weeks after randomization]
In each arms among non progressive patients after the 6 first cycles of Trabectedin : occurrence of progression or death 24 weeks after the date of randomization. Intention to treat analysis. Centralised radiological review.

Secondary Outcome Measures

Response rate [6, 12 and 18 weeks after randomization]
stabilisation, complete and partial responses according to RECIST 1.1
Progression free survival rates [12 and 54 weeks after randomization]
According to RECIST 1.1
Survival rates [12 and 24 months after randomization]
Median progression-free and median overall survivals [Up to 5 years after randomization]
Tolerability - safety [Up to 30 days after the last study drg administration]
According to NCI-CTC V4.0 scale
Clinical and biological predictive factors for non progression at the 6th cycle [At baseline]
Collected data at baseline : age, gender, comorbidity, disease history, previous treatment, tumor description, biological parameters
Post-randomization cost of care [For one year after randomization]
Cost of care will be evaluated by macro-costing approach
Self estimation of general health status [For 1 year after randomization]
Evaluation every 6 weeks by 100-mm-long horizontal visual analog scale (VAS) that ranged from worst imaginable health (as bad as death, 0) to perfect health

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria (for the selection part):

Inoperable or metastatic soft tissue sarcoma and/or uterine sarcoma
Measurable lesions (RECIST 1.1)
Performance status ≤ 2
Age ≥ 18
Normal hematological parameters (polynuclear neutrophils ≥ 1500, hemoglobin level ≥ 9 g/dl, platelets counts ≥ 100,000)
Adequate biological parameters :
Adequate hepatic function (bilirubin ≤ ULN , SGPT/ALT and SGOT/AST ≤ 2.5 x ULN)
Alkaline phosphatases ≤ 2.5 x ULN, If Alkaline phosphatases ≥ 2.5 ULN, hepatic isoenzymes 5-nucleotidases or GGT tests must be performed; hepatic isoenzymes 5- nucleotidases and/or GGT must be within the normal range
Albumin ≥ 25 g/L
Adequate renal function : Serum creatinine ≤ 1.5 x ULN
Creatine phosphokinase ≤ 2.5 x ULN
Adequate central venous access
Pregnant or lactating women or men of reproductive potential must use effective contraceptive methods
Patient covered by government health insurance
Information sheet given to the patient (Patient information sheet 1)

Exclusion Criteria (for the selection part):

Patients that have received more than one regimen of chemotherapy for metastatic or inoperable soft tissue or uterine sarcoma, after the failure/intolerance of doxorubicin and ifosfamide. Maintenance treatment does not count as treatment line
The following histological subtypes : GIST, rhabdomyosarcoma, aggressive fibromatosis, desmoïd tumour, PNET, carcinosarcoma, and all bone sarcomas
Single tumour in an irradiated region
Other malignant tumour over the past five years (except basal cell carcinoma or cervical carcinoma in situ adequately treated)
Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] Version 4.02). Known HIV1, HIV2, hepatitis B or hepatitis C infections
Presence of known leptomeningeal or brain metastasis
Patients unable to receive corticotherapy
Any circumstance that could jeopardise compliance or proper follow-up during the trial
Pregnant or nursing women

Inclusion Criteria (for the randomized part):

Patient registered in the selection part
Stable tumour or objective response (CR + PR) after 6 Trabectedin (Yondelis®) cycles, according to local assessment
Available copies of thoraco-abdominal and pelvic scan performed prior to the first cycle and after the sixth cycle
Performance status ≤ 2
Patients receiving at least 1 mg/m²/3 weeks of Trabectedin at the time of the sixth cycle
Normal hematological parameters (polynuclear neutrophils ≥ 1500, hemoglobin level ≥ 9 g/dl, platelets counts ≥ 100,000)
Adequate biological parameters :
Adequate hepatic function (bilirubin ≤ ULN , SGPT/ALT and SGOT/AST ≤ 2.5 x ULN)
Alkaline phosphatases ≤ 2.5 x ULN, If Alkaline phosphatases ≥ 2.5 ULN, hepatic isoenzymes 5-nucleotidases or GGT tests must be performed; hepatic isoenzymes 5- nucleotidases and/or GGT must be within the normal range
Albumin ≥ 25 g/L
Adequate renal function : Serum creatinine ≤ 1.5 x ULN
Creatine phosphokinase (CPK) ≤ 2.5 x ULN
Adequate central venous access
Pregnant or lactating women or men of reproductive potential must use effective contraceptive methods
Informed consent form signed by the patient or the patient's legal representative (patient information sheet 2 and informed consent)

Exclusion Criteria (for the randomized part):

Tumour progression (according to RECIST 1.1) during the first six Yondelis cycles
Non-availability of baseline scans prior to the first cycle and following the sixth cycle
Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] Version 4.02). Known HIV1, HIV2, hepatitis B or hepatitis C infections
Presence of known leptomeningeal or brain metastasis
Creatinine clearance less than 30 ml/min
Patients unable to receive corticotherapy
Any circumstance that could jeopardise compliance or proper follow-up during the trial
Pregnant or nursing women
Hypersensitivity to Trabectedin or any excipient in prior cycles

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Saint-Jacques Hospital	Besancon	France	25 000
2	Institut Bergonié	Bordeaux	France	33076
3	Centre François Baclesse	Caen	France	14076
4	Centre Jean Perrin	Clermont Ferrand	France	63011
5	Centre Georges François Leclerc	Dijon	France	21079
6	Centre Oscar Lambret	Lille	France	59020
7	Léon Bérard Center	Lyon	France	69 008
8	Centre Léon Bérard	Lyon	France	69008
9	Paoli Calmette Institute	Marseille	France	13 273
10	CHU Timone Adultes	Marseille	France	13385
11	Centre Antoine Lacassagne	Nice	France	06189
12	Institut Curie	Paris	France	75005
13	Centre Henri Becquerel	Rouen	France	76038
14	Centre René Huguenin	St Cloud	France	92210
15	Institut Claudius Regaud	Toulouse	France	31052
16	Institut Gustave Roussy	Villejuif	France	94805

Sponsors and Collaborators

Centre Oscar Lambret
French Sarcoma Group
Study Group of Bone Tumors

Investigators

Principal Investigator: Nicolas PENEL, MD, PhD, Centre Oscar Lambret

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Centre Oscar Lambret

ClinicalTrials.gov Identifier:

NCT01303094

Other Study ID Numbers:

T-DIS-1001

First Posted:

Feb 24, 2011

Last Update Posted:

May 31, 2019

Last Verified:

May 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Sarcoma

Trabectedin

Study Results

No Results Posted as of May 31, 2019