TRABECTEDIN for Advanced/metastatic soft tissue sarcoma | Osteosarcoma | Chondrosarcoma | Ewing sarcoma | Rhabdomyosarcoma | Desmoplastic small round cell tumor

Inclusion criteria

• {"criterion_text":"- 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.\n- Performance status ≤ 1 (ECOG).\n- Adequate respiratory functions: FEV1 > 1L; DLCO > 40% (patients with pulmonary target lesions).\n- 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.\n- 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.\n- Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.\n- 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)\n- Patient must have a central venous catheter for treatment, required for trabectedin administration.\n- Age: 16-75 years.\n- 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).\n- 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.\n- 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.\n- Patients must have documentation of disease progression within 6 months prior to study entry.\n- 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.\n- 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)\n- Measurable disease, according to RECIST v1.1 criteria."}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"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)."}

Secondary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"ORR defined as number with BOR of CR or PR considering all lesions divided by number of response-evaluable subjects (RECIST v1.1; central radiology review)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFSR at 6 months defined as percentage of patients without progression (all lesions) or death from enrollment until month 6 (RECIST v1.1; central radiology review)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"mPFS defined as median time in months between enrollment and progression (all lesions) or death (RECIST v1.1; central radiology review)."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"TTP defined as time in months between enrollment and progression of irradiated nodules (excluding deaths) per RECIST v1.1; central radiology review."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"OS defined as time in months between enrollment and death due to any cause; censored at last known alive date."}
• {"endpoint_text":"- 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…).","definition_or_measurement_approach":"Pain measured by BPI-SF; assessed day 1 of each cycle until cycle 10, then day 1 every other cycle (per schedule described)."}
• {"endpoint_text":"- 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…).","definition_or_measurement_approach":"QoL measured by QLQ-C30 EORTC v3.0; assessed at baseline (within 7 days of enrollment), day 1 each cycle until cycle 10, then day 1 every other cycle."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Safety assessed by AE type/incidence/severity/time/related causes via physical exam and labs; graded per CTCAE v5.0."}

Spain

Earliest CTIS Part Ii Submission Date

15-05-2024

Latest Decision Or Authorization Date

22-05-2024

Processing Time Days

7

Number Of Sites

10

Number Of Participants

72

Primary sponsor

Full Name

Asoc Grupo Espanol De Investigacion En Sarcomas

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Contract research organisations

Name

Sofpromed Investigacion Clinica S.L.

Responsibilities

sponsorDuties code 12; contact email: ensayos@sofpromed.com

Third parties

• {"country":"Spain","full_name":"Sofpromed Investigacion Clinica S.L.","duties_or_roles":"sponsorDuties code 12; contact email: ensayos@sofpromed.com","organisation_type":"Hospital/Clinic/Other health care facility"}