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Soft Tissue SarcomaPhase 2SYNERGIASNCT05131386

Multicohort Trial of Trabectedin and Low-dose Radiation Therapy in Advanced/Metastatic Sarcomas

A Phase 2 study testing Trabectedin in people with Soft Tissue Sarcoma and Bone Tumors, run by Grupo Espanol de Investigacion en Sarcomas at 7 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Phase II, multicohort, single arm, open-label, multicenter, international clinical trial with three cohorts (cohort A: Soft tissue sarcoma, cohort B: Bone tumors (osteosarcoma, chondrosarcoma and cohort C: Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other… Read more about this study

Who is it for?
Ages 16 to 75 years
What is being tested?
Trabectedin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
85 participants
Where
7 sitesSpain
Study dates
28 May 2021to 28 Jul 2024
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 16 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
  • Age: 16-75 years.
  • Patients must have a diagnosis of soft tissue sarcoma (cohort A), bone tumors (osteosarcoma, chondrosarcoma) (cohort B) or small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas) (cohort C), with metastasis or locally advanced disease, and not suitable for metastasectomy or surgical resection or not oncologically recommended metastasectomy. A centralized diagnosis will be performed, and the central diagnosis confirmation will be mandatory prior to enrollment (tumor sample must be available and sent during screening).
  • Disease distribution allows meeting with normal tissue constraints of radiation therapy. Radiation oncologist must confirm this point, taking into account that the dose for extremities will be 45 Gy while for non-extremity will be 30 Gy.
  • Those lesions considered for radiation therapy must be related with a clinically relevant symptom. It is not necessary to irradiate all the lesions within one organ. Irradiating pulmonary lesions with infiltration of pleural serosa should be discouraged.
  • Patients must have documentation of disease progression within 6 months prior to study entry.
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  • The patient must have been considered eligible for systemic chemotherapy. Patients should had received at least one line of systemic therapy (anthracycline-based in the case of Cohort A-STS, unless the patient is not candidate for treatment with anthracyclines), with a maximum of three previous lines for advanced/metastatic disease are allowed as long as trabectedin has not been included.
  • The following sarcoma types are eligible:
  • Soft tissue sarcoma
  • Bone tumors (osteosarcoma, chondrosarcoma)
  • Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas)
  • Measurable disease, according to RECIST v1.1 criteria.
  • Performance status ≤ 1 (ECOG).
  • Adequate respiratory functions: FEV1 > 1L; DLCO > 40% (patients with pulmonary target lesions).
  • Adequate bone marrow function (hemoglobin ≥ 9 g/dL, leukocytes ≥ 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,500/mm3, platelets ≥ 100,000/mm3). Patients with creatinine clearance (based on Cockroft and Gault) ≥30 ml/min, albumin ≥ 25 g/L, ALT and AST ≤ 2.5 times the ULN, total bilirubin ≤ ULN, CPK ≤ 2.5 times ULN, alkaline phosphatase ≤ 2.5 times the ULN are acceptable. If the increase of alkaline phosphatase is > 2.5 times the ULN, then the alkaline phosphatase liver fraction and/or GGT must be ≤ ULN.
  • Men or women of childbearing potential must use an effective method of contraception before entry into the study and throughout the trial treatment and for 6 months after the last dose of trabectedin. Women of childbearing potential must have a negative urine pregnancy test before study entry.
  • Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.
  • HBV and HCV serologies must be performed prior to enrollment. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. If a potential patient is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the patient should NOT be included in the study (if a qualitative PCR cannot be performed then patient will not be able to enter the study)
  • Patient must have a central venous catheter for treatment, required for trabectedin administration.

Who cannot join

  • Previous treatment with trabectedin or previous treatment with radiotherapy (this latter just in case the previous radiotherapy treatment does not allow the radiotherapy treatment of this study due to tissue constrains).
  • Liver inclusion in irradiation fields is not permitted, not even partially.
  • Normal tissue constrains for radiation therapy.
  • Performance status ≥ 2 (ECOG).
  • Plasma bilirubin > ULN.
  • Creatinine clearance <30ml/min.
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  • History of other neoplastic disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated or no evidence of recurrence for more than 5 years after primary tumor treatment.
  • Severe chronic obstructive pulmonary disease (COPD) or other severe pulmonary diseases.
  • Significant cardiovascular disease (for example, dyspnea > 2 NYHA).
  • Significant systemic diseases grade 3 or higher on the NCI-CTCAE v5.0 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity.
  • Uncontrolled bacterial, mycotic or viral infections.
  • Known positive test for infection by human immunodeficiency virus (HIV).
  • Women who are pregnant or breast-feeding.
  • Psychological, familiar, social or geographic circumstances that limit the patient's ability to comply with the protocol or informed consent.
  • Patients who have participated in another clinical trial and/or have received any other investigational product in the last 30 days prior to enrollment.
  • Histologies other than those described in inclusion criteria.

Trial locations and contacts

7 sites in 1 country.

Patricio Ledesma contact

971439900 ext. +34

ensayos@sofpromed.com

7 sites in 1 country

Spain7 sites, 7 recruiting

  • Hospital Universitari Vall d'Hebrón

    Barcelona, Catalonia, 08035

    Claudia Valverde

    Recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, Catalonia, 08041

    Katarina Majercakova

    Recruiting

  • Hospital General Universitario Gregorio Marañón

    Madrid, Madrid, 28009

    Rosa Álvarez

    Recruiting

  • Hospital Clínico San Carlos

    Madrid, Madrid, 28040

    Antonio Casado

    Recruiting

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, Madrid, 28040

    Javier Martín Broto

    Recruiting

  • Hospital Universitario La Paz

    Madrid, Madrid, 28046

    Andrés Redondo

    Recruiting

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife, Canary Islands, 38320

    Josefina Cruz

    Recruiting

Other trials in Spain

About this study

Official title: Phase II Multicohort Trial of Trabectedin and Low-dose Radiation Therapy in Advanced/Metastatic Sarcomas

Phase II, multicohort, single arm, open-label, multicenter, international clinical trial with three cohorts (cohort A: Soft tissue sarcoma, cohort B: Bone tumors (osteosarcoma, chondrosarcoma and cohort C: Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas)) with 7 sites in Spain.

Main objective: To evaluate the overall response rate (ORR) in the irradiated nodules according to RECIST v1.1 criteria.

Read more

Treatment

Medication

Trabectedin at 1.5 mg/m2 24-h IV CI along with radiation therapy (30 Gy, 3 Gy/day for 10 days for non-extremity location and 45 Gy, 1.8 Gy/day for 25 days for extremity location of target lesion(s)), starting within 1 hour after the first trabectedin infusion withdrawal (day 2)) will be given every 3 weeks up to progression or intolerance.

Premedication

4 mg oral dexamethasone 24h and 12h before trabectedin administration, 20 mg IV dexamethasone 30 minutes before treatment. Ondansetron or analogue will also be given prior to trabectedin.

Read the detailed description

Cohort A: Soft tissue sarcomas (2nd or further line): A proportion of 10% of ORR will be considered as not promising, whereas an ORR of 35% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 27 patients were estimated in this cohort. With Simon's two-stage optimal design,36 at least 2 responses have to be obtained over the 11 first patients. Then, additional 16 eligible patients will be accrued up to 27 patients. If at least 6 patients show response, further investigation of this scheme is warranted.

Cohort B: Bone tumors (osteosarcoma, chondrosarcoma) (2nd or further line): A proportion of 3% of ORR will be considered as not promising, whereas an ORR of 20% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 29 patients were estimated in this cohort. With Simon's two-stage optimal design,36 at least 1 response has to be obtained over the 12 first patients. Then, additional 17 eligible patients will be accrued up to 29 patients. If at least 3 patients show response, further investigation of this scheme is warranted.

Cohort C: Small round-cell sarcomas (Ewing's sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round-cell sarcomas) (3rd or further line): A proportion of 15% of ORR will be considered as not promising, whereas an ORR of 40% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 29 patients were estimated in this cohort. With Simon's two-stage optimal design,36 at least 3 response has to be obtained over the 13 first patients. Then, additional 16 eligible patients will be accrued up to 29 patients. If at least 8 patients show response, further investigation of this scheme is warranted.

Taking into account that 10% of enrolled patients might not be evaluable (losses), an extra amount of 3 patients may be recruited per cohort.

Being tested
Trabectedin
Keywords
Osteosarcoma, Chondrosarcoma, Ewing's sarcoma, Rhabdomyosarcoma, Desmoplastic small round-cell tumors
Medical subject headings
Sarcoma, Bone Neoplasms, Osteosarcoma, Chondrosarcoma, Sarcoma, Ewing, Rhabdomyosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrabectedinDrug

    Also called Yondelis

    ET-743, Yondelis (vials of 1 mg). Route of administration: intravenous infusion

Study groups in NCT05131386
Study groupRoleWhat they receive
Multicohort trial of trabectedin and low-dose radiation therapy in advanced/metastatic sarcomasExperimentalPremedication 4 mg oral dexamethasone 24h and 12h before trabectedin administration, 20 mg IV dexamethasone 30 minutes before treatment. Ondansetron or analogue will also be given prior to trabectedin. Medication Trabectedin at 1.5 mg/m2 24-h IV CI along with radiation therapy (30 Gy, 3 Gy/day for 10 days for non-extremity location and 45 Gy, 1.8 Gy/day for 25 days for extremity location of target lesion(s)), starting within 1 hour after the first trabectedin infusion withdrawal (day 2)) will be given every 3 weeks up to progression or intolerance.
Receives: Drug: Trabectedin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR) in the irradiated nodules

    ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) only in the irradiated nodules divided by the number of response evaluable subjects (according to RECIST v1.1 criteria and based on central radiology review). This is considered a good surrogate for palliative relief.

    Measured: 6 weeks

Secondary outcomes (8)

  1. Overall response rate (ORR) considering all the lesions

    ORR is defined as the number of subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) considering all the lesions divided by the number of response evaluable subjects (according to RECIST v1.1 criteria and based on central radiology review).

    Measured: 6 weeks

  2. Progression-free survival rate (PFSR) at 6 months considering all the lesions

    Efficacy measured by the PFSR at 6 months according to RECIST v1.1 criteria based on central radiology review. PFSR at 6 months is defined as the percentage of patients who did not experience progression (considering all the lesions) or death due to any cause since the date of enrollment until month 6 after date of enrollment.

    Measured: 6 months

  3. Median progression-free survival (mPFS)

    Efficacy measured by the mPFS according to RECIST v1.1 criteria based on central radiology review. mPFS is defined as the median of time in months between the date of enrollment and the date of progression (considering all the lesions) or death due to any cause.

    Measured: 6 months

  4. Time to progression (TTP) of irradiated nodules

    TTP is defined as the time in months between the date of enrollment and the date of progression of irradiated nodules (not including deaths) (according to RECIST v1.1 criteria and based on central radiology review).

    Measured: 6 weeks

  5. Overall survival (OS)

    OS is defined as the time in months between the date of enrollment and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.

    Measured: 6 months

  6. Variations in pain using the Brief Pain Inventory - Short Form (BPI-SF)

    Variations from baseline will be assessed on day 1 of every cycle (before trabectedin administration) until cycle 10 and then on day 1 every other cycle (cycle 12 day 1, cycle 14 day 1…).

    Measured: 3 weeks

  7. Variations in quality of life using the QLQ-C30 EORTC v3.0 questionnaire.

    Variations in quality of life will be assessed at baseline (within 7 days with respect to enrollment), on day 1 of every cycle (before trabectedin administration) until cycle 10 and then on day 1 every other cycle (cycle 12 day 1, cycle 14 day 1…).

    Measured: 3 weeks

  8. Safety profile measured by adverse event type, incidence, severity, time of appearance, and related causes

    Toxicity will be assessed through physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE v5.0.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2021
  2. Study start28 May 2021
  3. Primary completion28 Jul 2024 (estimated)
  4. Study completion28 Jul 2024 (estimated)

Resources

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
Model description
Phase II, multicohort, single arm, open-label, multicenter, international clinical trial
Masking
None (open label)
Enrolment
85 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05131386
Sponsor's protocol ID
GEIS-75
Acronym
SYNERGIAS
Status last verified
Mar 2023
First submitted
11 Nov 2021
Last updated
27 Mar 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trabectedin in people with Soft Tissue Sarcoma and Bone Tumors, run by Grupo Espanol de Investigacion en Sarcomas at 7 sites in Spain.

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 19 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 27 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Spain. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Patricio Ledesma (971439900 ext. +34, ensayos@sofpromed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) in the irradiated nodules (time frame: 6 weeks). 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 NCT05131386.

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 27 Mar 2023.

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