Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma

NCT ID: NCT01303094

Last Updated: 2019-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2018-08-09

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

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

Conditions

Soft Tissue Sarcoma; Uterine Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continuation of Trabectedin

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

Group Type: OTHER

Trabectedin

Intervention Type: DRUG

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.

"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

Group Type: OTHER

Drug: holiday

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: OTHER

Other Intervention Names

Yondelis; No drug

Eligibility Criteria

Inclusion Criteria

• 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)

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

French Sarcoma Group

OTHER

Sponsor Role: collaborator

Study Group of Bone Tumors

OTHER

Sponsor Role: collaborator

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicolas PENEL, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret

Locations

Saint-Jacques Hospital

Besançon, , France

Institut Bergonié

Bordeaux, , France

Centre François Baclesse

Caen, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Georges François Leclerc

Dijon, , France

Centre Oscar Lambret

Lille, , France

Léon Bérard Center

Lyon, , France

Centre Léon Bérard

Lyon, , France

Paoli Calmette Institute

Marseille, , France

CHU Timone Adultes

Marseille, , France

Centre Antoine Lacassagne

Nice, , France

Institut Curie

Paris, , France

Centre Henri Becquerel

Rouen, , France

Centre René Huguenin

Saint-Cloud, , France

Institut Claudius Regaud

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

Le Cesne A, Blay JY, Domont J, Tresch-Bruneel E, Chevreau C, Bertucci F, Delcambre C, Saada-Bouzid E, Piperno-Neumann S, Bay JO, Mir O, Ray-Coquard I, Ryckewaert T, Valentin T, Isambert N, Italiano A, Clisant S, Penel N. Interruption versus continuation of trabectedin in patients with soft-tissue sarcoma (T-DIS): a randomised phase 2 trial. Lancet Oncol. 2015 Mar;16(3):312-9. doi: 10.1016/S1470-2045(15)70031-8. Epub 2015 Feb 11.

Reference Type: DERIVED

PMID: 25680558 (View on PubMed)

Other Identifiers

T-DIS-1001

Identifier Type: -

Identifier Source: org_study_id