ECUBECTEDIN for Soft tissue sarcoma|Other solid tumors

Inclusion criteria

• {"criterion_text":"- Patients must voluntarily sign the informed consent before any study test is conducted that is not part of routine patient care. (All cohorts)\n- Patients must have a diagnosis of advanced soft tissue sarcoma, or recurrent head & neck suitable for reirradiation or other advanced or metastatic solid tumor not suitable for metastasectomy or surgery resection or not oncologically recommended metastasectomy. A centralized diagnosis will be performed, and the tumor sample must be available and sent prior to PM14 start. For phase II part, only soft tissue sarcomas will be enrolled. (Cohort C).\n- Patients must have received a previous chemotherapy line in advanced disease. (Cohort C)\n- A centralized diagnosis of sarcoma, which includes: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, leiomyosarcoma, sclerosing epithelioid fibrosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumors, sarcoma NOS, fibrosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, epithelioid sarcoma, clear cell sarcoma, dedifferentiated or aggressive features in solitary fibrous tumor, extraskeletal myxoid chondrosarcoma, angiosarcoma, epithelioid hemangioendothelioma, … A centralized diagnosis of DD liposarcoma or myxoid/hypercellular liposarcoma or leiomyosarcoma must be confirmed for patients in cohort E. (Cohorts A, B, E, and F)\n- Disease distribution must allow meeting with normal tissue constrains of radiation therapy. Radiation oncologist must confirm this point at local sites. (Cohort C).\n- Metastatic spread could be present in several organs (i.e., lungs and pelvic fossa) however, not all the locations have to be irradiated. (Cohort C).\n- Those lesions considered for radiation therapy have to be related to symptoms (for phase II). (Cohort C).\n- It is allowed that not all the lesions will be under radiation fields. As a general rule, the priority is to select, as target-irradiating lesions, those with greater increase in size and those largest lesions if related to symptoms. Irradiating pulmonary lesions with infiltration of pleural serosa is discouraged. (Cohort C).\n- Radiological disease progression must be documented within 6 months prior to study entry. (Cohort C)\n- Patients must have been considered eligible for systemic chemotherapy. A maximum of three previous lines in phase I and two previous lines in phase II for advanced/metastatic disease are allowed. (Cohort C).\n- The following histological subtypes can be included for the phase II part (central pathology review is mandatory before accrual): undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma, angiosarcoma, epithelial hemangioendothelioma, liposarcoma and its variants (well differentiated, dedifferentiated, myxoid/round cell, pleomorphic), synovial sarcoma, fibrosarcoma and its variants (epithelial fibrosarcoma/low grade fibromyxoid sarcoma), solitary fibrous tumor, malignant peripheral nerve sheath tumor (MPNST), myxofibrosarcoma, epithelioid sarcoma and (NOS) unclassified sarcoma. (Cohort C)\n- Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA. (All cohorts.)\n- Patients must have received a previous chemotherapy line in advanced disease unless contraindicated or not indicated. (Cohorts A, B, E, and F)\n- Radiological disease progression must be documented within 6 months prior to study entry. (Cohorts A, B, E, and F.)\n- The patient must have been considered eligible for systemic chemotherapy. A maximum of two previous lines for advanced/metastatic disease are allowed. (CohortsA, B, E and F.)\n- Age: 18-75 years. (All cohorts.)\n- Measurable disease according to RECIST v1.1 criteria. (All cohorts)\n- Performance status ≤1 (ECOG).\n- Men or women of childbearing potential must be using an effective method of contraception before entry into the study and throughout the same and for 3 months (men) and 6 months (women) after ending study treatment. Women of childbearing potential must have a negative serum or urine pregnancy test before study entry. (All cohorts.)\n- Patients must have a diagnosis of localized soft tissue sarcoma that lacks one or more of the following risk criteria: G3, deep and > 5 cm. At least G2 is required (i.e., G3, superficial and > 5 cm; or G3 < 5 cm deep; or G2, deep and > 5 cm, etc.). (Cohort D)\n- Patients must be diagnosed by core-biopsy and the elapsed time between biopsy and enrollment must be shorter than 6 weeks. (Cohort D)\n- Patients must be diagnosed by central pathology review with one of the following subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, synovial sarcoma, sarcoma NOS, fibrosarcoma, myxoid liposarcoma, dedifferentiated liposarcoma, solitary fibrous tumor (the formerly malignant subtype). (Cohort D)\n- Patient must have a central venous catheter for PM14 treatment. (All cohorts)\n- Patients must have a diagnosis of soft tissue sarcoma with metastasis, and not suitable for metastasectomy or surgery resection or not oncologically recommended metastasectomy. A centralized diagnosis confirmation will be performed and the tumor sample must be available and sent prior to inclusion to this end. (Cohorts A, B, E, and F: PM14 monotherapy in advanced disease)\n- A centralized diagnosis of sarcoma, which includes: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, leiomyosarcoma, sclerosing epithelioid fibrosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumors, sarcoma NOS, fibrosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, epithelioid sarcoma, clear cell sarcoma, dedifferentiated or aggressive features in solitary fibrous tumor, extraskeletal myxoid chondrosarcoma, angiosarcoma, epithelioid hemangioendothelioma, well-differentiated/dedifferentiated liposarcoma and myxoid liposarcoma. A centralized diagnosis of DD liposarcoma or myxoid/hypercellular liposarcoma or leiomyosarcoma must be confirmed for patients in cohort E. (Cohorts A, B, E and F)\n- Patients must have received a previous chemotherapy line in advanced disease, unless contraindicated or not indicated. (Cohorts A, B, E and F).\n- Radiological disease progression must be documented within 6 months prior to study entry. (Cohorts A, B, E and F).\n- Patients must have been considered eligible for systemic chemotherapy. A maximum of three previous lines in cohorts A and B and two previous lines in cohorts E and F for advanced/metastatic disease are allowed. (Cohorts A, B, E and F)."}

Exclusion criteria

• {"criterion_text":"- Performance status ≥ 2 (ECOG). (All cohorts)\n- Psychological, family, social or geographic circumstances that limit the patients’ ability to comply with the protocol or informed consent. (All cohorts).\n- Patients participating in another clinical trial or receiving any other investigational product. (All cohorts).\n- Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to PM14 start. (All cohorts).\n- Prior treatment with lurbinectedin, trabectedin or PM14. (All cohorts).\n- Histologies other than those described in the inclusion criteria. (Cohorts A, B, E and F).\n- Previous treatment with radiotherapy (except if previous radiotherapy treatment plus planned study radiotherapy treatment allow tissue constrains). (Cohort C).\n- Severe COPD or other severe pulmonary diseases. (Cohort C).\n- Histologies other than those described in inclusion criteria. (Cohort C).\n- High-risk localized patients are not allowed to be enrolled (those G3, deep, and larger than 5 cm or those with at least 40% risk of death by sarculator nomogram). (Cohort D).\n- Previous treatment with radiotherapy. (Cohort D)\n- Plasma bilirubin > ULN. (All cohorts).\n- Primary tumor location other than those indicated in the inclusion criteria. (Cohort D)\n- Histological subtypes other than those indicated in the inclusion criteria. (Cohort D).\n- Unresectable or inoperable primary tumor. (Cohort D)\n- Creatinine > 1.6 mg/dL. (Todas las cohortes).\n- History of other cancer with less than 5 years free of disease with the exception of adequately treated basal cell carcinoma or in situ cervical cancer. (All cohorts).\n- Patients who do not provide consent for mandatory biological samples cannot participate in the study. (All cohorts).\n- Significant cardiovascular disease (for example, dyspnea > 2 NYHA). (All cohorts).\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 significantly contribute to treatment toxicity. (All cohorts).\n- Uncontrolled bacterial, mycotic or viral infections. (All cohorts).\n- Women who are pregnant or breastfeeding. (All cohorts)."}

Primary endpoints

• {"endpoint_text":"- COHORTS A AND B Phase I: The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol.","definition_or_measurement_approach":"MTD determined by assessing adverse events according to CTCAE v5.0 and used as rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol."}
• {"endpoint_text":"- COHORTS E AND F Phase II: PFSR-6m (according to central radiology review): Efficacy measured by the PFSR at 6 months, which is defined as the percentage of patients who did not experience radiological progression according to RECIST v1.1 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 radiological progression per RECIST v1.1 or death from enrollment until month 6 (central radiology review)."}
• {"endpoint_text":"- COHORT C Phase I: The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol.","definition_or_measurement_approach":"MTD determined by adverse events per CTCAE v5.0; used for dose escalation/diminution rules as per protocol."}
• {"endpoint_text":"- COHORT C. Phase II: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1). Only nodules included in the radiation field will be considered.","definition_or_measurement_approach":"ORR defined as proportion of patients with BOR of CR or PR per RECIST v1.1 (central radiology review); only nodules in radiation field counted."}
• {"endpoint_text":"- COHORT D. Phase I: The MTD will be determined by assessing adverse events according to CTCAE v5.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose -limiting toxicities detailed in the protocol.","definition_or_measurement_approach":"MTD determined by adverse events per CTCAE v5.0 and used for escalation/dose-limiting toxicity-based rules."}
• {"endpoint_text":"- COHORT D. Phase II: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR defined as proportion with BOR of CR or PR per RECIST v1.1 (central radiology review)."}

Secondary endpoints

• {"endpoint_text":"- COHORTS A AND B. Phase I. Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Toxicity assessed via adverse events related to study drugs, detected by physical exams and labs, graded per CTCAE v5.0."}
• {"endpoint_text":"- COHORTS A AND B. Phase I: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR per RECIST v1.1 assessed by central radiology review."}
• {"endpoint_text":"- COHORTS A AND B. Phase I. mPFS (according to central radiology review): Efficacy measured by mPFS, which is defined as the median of time in months from date of enrollment to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.","definition_or_measurement_approach":"mPFS defined as median time (months) from enrollment to radiological progression per RECIST v1.1 or death (central radiology review)."}
• {"endpoint_text":"- COHORTS A AND B. Phase I: Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.","definition_or_measurement_approach":"Quality of life measured by EORTC QLQ-C30."}
• {"endpoint_text":"- COHORTS A AND B. Phase I: The clinical study will provide tumor and blood samples for the translational research program.","definition_or_measurement_approach":"Provision of tumor and blood samples for translational research."}
• {"endpoint_text":"- COHORTS A AND B. Phase I: The clinical study will provide blood samples for the measurement of PM14 concentration and baseline α-1-acid glycoprotein (AAG) levels.","definition_or_measurement_approach":"Blood samples to measure PM14 concentration and baseline AAG levels."}
• {"endpoint_text":"- COHORTS E AND F. Phase II: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR per RECIST v1.1 assessed by central radiology review."}
• {"endpoint_text":"- COHORTS E AND F. Phase II: mOS: Efficacy measured by mOS, which is defined as the median of time in months from date of enrollment to date of death due to any cause. OS will be censored on the last date a patient was known to be alive.","definition_or_measurement_approach":"mOS defined as median time (months) from enrollment to death from any cause; censor at last known alive date."}
• {"endpoint_text":"- COHORTS E AND F. Phase II: Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.","definition_or_measurement_approach":"Quality of life measured by EORTC QLQ-C30."}
• {"endpoint_text":"- COHORTS E AND F. Phase II: Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Toxicity assessed via adverse events and labs, graded per CTCAE v5.0."}
• {"endpoint_text":"- COHORTS E AND F. Phase II: The clinical study will provide tumor and blood samples for the translational research program.","definition_or_measurement_approach":"Tumor and blood samples collected for translational research."}
• {"endpoint_text":"- COHORT C. Phase I: Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Toxicity assessed via adverse events and labs, graded per CTCAE v5.0."}
• {"endpoint_text":"- COHORT C. Phase I: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR per RECIST v1.1 assessed by central radiology review."}
• {"endpoint_text":"- COHORT C. PHase I: Median of progression-free survival (mPFS) (according to central radiology review): Efficacy measured by mPFS, which is defined as the median of time in months from date of enrollment to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.","definition_or_measurement_approach":"mPFS defined as median time from enrollment to radiological progression per RECIST v1.1 or death (central radiology review)."}
• {"endpoint_text":"- COHORT C. Phase I: Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire.","definition_or_measurement_approach":"Quality of life measured by EORTC QLQ-C30."}
• {"endpoint_text":"- COHORT C. Phase I: The clinical study will provide tumor and blood samples for the translational research program.","definition_or_measurement_approach":"Tumor and blood samples for translational research."}
• {"endpoint_text":"- COHORT C. Phase II: Changes in pain: Variations in pain will be measured by the Brief Pain Inventory – Short Form (BPI-SF). (Further information in the protocol)","definition_or_measurement_approach":"Pain variations measured by BPI-SF."}
• {"endpoint_text":"- COHORT C. Phase II: Changes in analgesic use: Variations in analgesic use will be measured by the Analgesic Quantification Algorithm (AQA). (More information in the protocol.)","definition_or_measurement_approach":"Analgesic use measured by Analgesic Quantification Algorithm (AQA)."}
• {"endpoint_text":"- COHORT C. Phase II: Changes in quality of life measured by the QLQ-C30 EORTC v3.0 questionnaire. The proportions of patients showing little (5-10 points), moderate (11-20 points) or high changes (> 20) in pain and dyspnea (and other symptoms scales if applicable) over time. • The proportions of patients showing little (5-10 points), moderate (11-20 points) or high changes (> 20) in global health status scales over time.","definition_or_measurement_approach":"Quality of life measured by QLQ-C30 EORTC v3.0; categorize changes by point thresholds as specified."}
• {"endpoint_text":"- COHORT C. Phase II: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR per RECIST v1.1 assessed by central radiology review."}
• {"endpoint_text":"- COHORT C. Phase II: Time to progression (TTP) of irradiated nodules (according to central radiology review): 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).","definition_or_measurement_approach":"TTP defined as months from enrollment to progression of irradiated nodules per RECIST v1.1 (deaths not included)."}
• {"endpoint_text":"- COHORT C. Phase II: PFSR-6m (according to central radiology review): Efficacy measured by the PFSR at 6 months, which is defined as the percentage of patients who did not experience radiological progression according to RECIST v1.1 or death due to any cause since the date of enrollment until month 6 after date of enrollment.","definition_or_measurement_approach":"PFSR-6m defined as % without progression per RECIST v1.1 or death within 6 months (central radiology review)."}
• {"endpoint_text":"- COHORT C. Phase II: mOS: Efficacy measured by mOS, which is defined as the median of time in months from date of enrollment to date of death due to any cause. OS will be censored on the last date a patient was known to be alive.","definition_or_measurement_approach":"mOS defined as median months from enrollment to death; censor at last known alive date."}
• {"endpoint_text":"- COHORT C. Phase II: Pathological response: Assessed using a predefined surgical specimen pathology form and method describing the precise percentage of tumor non-viable histological changes (hyalinosis, necrosis, cyst, differentiation etc) and percentage of viable tumor.","definition_or_measurement_approach":"Pathological response assessed by predefined surgical specimen pathology form quantifying non-viable histological changes and viable tumor percentage."}
• {"endpoint_text":"- COHORT C. Phase II: Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Toxicity graded per CTCAE v5.0 via AEs from exams and labs."}
• {"endpoint_text":"- COHORT C. Phase II: The clinical study will provide tumor and blood samples for the translational research program.","definition_or_measurement_approach":"Provision of tumor and blood samples for translational research."}
• {"endpoint_text":"- COHORT D. Phase I: Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Toxicity assessed via AEs and labs, graded per CTCAE v5.0."}
• {"endpoint_text":"- COHORT D. Phase I: Overall response rate (ORR) (according to central radiology review): Efficacy measured by ORR, which is defined as the number of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of response evaluable patients (according to RECIST v1.1).","definition_or_measurement_approach":"ORR per RECIST v1.1 assessed by central radiology review."}
• {"endpoint_text":"- COHORT D. Phase I: Median of progression-free survival (mPFS) (according to central radiology review): Efficacy measured by mPFS, which is defined as the median of time in months from date of enrollment to date of radiological progression according to RECIST v1.1 or to date of death due to any cause, whatever occurs first.","definition_or_measurement_approach":"mPFS defined as median time from enrollment to progression per RECIST v1.1 or death (central radiology review)."}
• {"endpoint_text":"- COHORT D. Phase I: Pathological response: Assessed using a predefined surgical specimen pathology form and method describing the precise percentage of tumor non-viable histological changes (hyalinosis, necrosis, cyst, differentiation etc) and percentage of viable tumor.","definition_or_measurement_approach":"Pathological response assessed by predefined pathology form quantifying non-viable changes and viable tumor percentage."}
• {"endpoint_text":"- COHORT D. Phase I: The clinical study will provide tumor and blood samples for the translational research program.","definition_or_measurement_approach":"Tumor and blood samples provided for translational research."}
• {"endpoint_text":"- COHORT D. Phase II: Pathological response: Assessed using a predefined surgical specimen pathology form and method describing the precise percentage of tumor non-viable histological changes (hyalinosis, necrosis, cyst, differentiation etc) and percentage of viable tumor.","definition_or_measurement_approach":"Pathological response assessed by predefined pathology method quantifying non-viable tumor and viable percentage."}
• {"endpoint_text":"- COHORT D. Phase II: Relapse-free survival (RFS) at 3 years: Efficacy measured by RFS at 3 years, which is defined as the percentage of patients who did not experience relapse since date of surgery until year 3 after date of surgery.","definition_or_measurement_approach":"RFS at 3 years defined as percent without relapse from surgery date until 3 years."}
• {"endpoint_text":"- COHORT D. Phase II: MRI imaging will be evaluated to assess variations in diffusion/perfusion parameters (exploratory).","definition_or_measurement_approach":"Exploratory MRI evaluation of diffusion/perfusion parameter changes."}
• {"endpoint_text":"- COHORT D. Phase II: Toxicity will be assessed by adverse events related to study drugs, detected through physical examinations and laboratory tests, and graded according to CTCAE v5.0.","definition_or_measurement_approach":"Toxicity graded per CTCAE v5.0 via AEs from exams and labs."}
• {"endpoint_text":"- COHORT D. Phase II: The clinical study will provide tumor and blood samples for the translational research program.","definition_or_measurement_approach":"Tumor and blood samples for translational research."}

Spain

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

19-12-2024

Processing Time Days

23

Number Of Sites

9

Number Of Participants

195

Primary sponsor

Full Name

Asoc Grupo Espanol De Investigacion En Sarcomas

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain

Third parties

• {"country":"Spain","full_name":"Sofpromed Investigacion Clinica S.L.","duties_or_roles":"sponsorDuties codes: 1,10,12,5,6,7; phone: 971439900; email: ensayos@sofpromed.com","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Kymos S.L.","duties_or_roles":"sponsorDuties codes: 4; phone: 935481848; email: mperez@kymos.com","organisation_type":"Pharmaceutical company"}