Clinical trial of trabectedin and low-dose radiation therapy in advanced/metastatic sarcomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asoc Grupo Espanol De Investigacion En Sarcomas

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 May 2024 → ongoing

Decision date (initial)

2024-05-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509215-81-00

EudraCT number

2019-003103-36

ClinicalTrials.gov

NCT05131386

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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

Secondary objectives 9

1. To evaluate the overall response rate (ORR) considering all the lesions according to RECIST v1.1 criteria.
2. To evaluate the progression-free survival rate (PFSR) at 6 months considering all the lesions according to RECIST v1.1 criteria.
3. To evaluate the median of progression free survival (mPFS) considering all the lesions according to RECIST v1.1 criteria.
4. To evaluate time to progression (TTP) of irradiated nodules according to RECIST v1.1 criteria.
5. To evaluate overall survival (OS).
6. To evaluate variations in pain.
7. To evaluate variations in analgesic use.
8. To evaluate variations in quality of life.
9. To evaluate the safety profile according to CTCAE v5.0.

Conditions and MedDRA coding

Adult and young adult patients with diagnosis of advanced/metastatic soft tissue sarcoma, bone tumors (osteosarcoma, chondrosarcoma) and small round-cell sarcomas (Ewing’s sarcoma, rhabdomyosarcoma, desmoplastic small round-cell tumors and other small round cell sarcomas) with measurable disease.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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.
2. Age: 16-75 years.
3. 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).
4. 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.
5. 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.
6. Patients must have documentation of disease progression within 6 months prior to study entry.
7. 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.
8. 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)
9. Measurable disease, according to RECIST v1.1 criteria.
10. Performance status ≤ 1 (ECOG).
11. Adequate respiratory functions: FEV1 > 1L; DLCO > 40% (patients with pulmonary target lesions).
12. 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.
13. 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.
14. Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.
15. 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)
16. Patient must have a central venous catheter for treatment, required for trabectedin administration.

Exclusion criteria 16

1. 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).
2. Liver inclusion in irradiation fields is not permitted, not even partially.
3. Normal tissue constrains for radiation therapy.
4. Performance status ≥ 2 (ECOG).
5. Plasma bilirubin > ULN.
6. Creatinine clearance <30ml/min.
7. 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.
8. Severe chronic obstructive pulmonary disease (COPD) or other severe pulmonary diseases.
9. Significant cardiovascular disease (for example, dyspnea > 2 NYHA).
10. 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.
11. Uncontrolled bacterial, mycotic or viral infections.
12. Known positive test for infection by human immunodeficiency virus (HIV).
13. Women who are pregnant or breast-feeding.
14. Psychological, familiar, social or geographic circumstances that limit the patient’s ability to comply with the protocol or informed consent.
15. Patients who have participated in another clinical trial and/or have received any other investigational product in the last 30 days prior to enrollment.
16. Histologies other than those described in inclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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.

Secondary endpoints 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).
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.
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.
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).
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.
6. Changes in pain: Variations in pain will be measured by 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…).
7. Changes in quality of life: Variations in quality of life will be measured by 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 10and then on day 1 every other cycle (cycle 12 day 1, cycle 14 day 1…).
8. Safety profile: toxicity will be assessed considering adverse event type, incidence, severity, time of appearance, related causes, through physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE v5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asoc Grupo Espanol De Investigacion En Sarcomas

Sponsor organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Address

Calle Del Conde De Aranda 20 Planta 5 Puerta Derecha

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Contact name

Adriana Rojo

Public contact point

Organisation

Asoc Grupo Espanol De Investigacion En Sarcomas

Contact name

Adriana Rojo

Third parties 1

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 1 file

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications