Advanced soft tissue sarcoma and other solid tumors
Conditions
Interventions
Product Name: PM14
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: PM14
Other descriptive name: PM14
Concentration unit: mg/m2 milligram(s)/square meter
Concentration
Sponsors
GRUPO ESPAÑOL DE INVESTIGACIÓN EN SARCOMAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All the cohorts: - The patient must voluntarily sign the informed consent before any study test is conducted that is not part of routine patient care. - Age: 18-75 years. - Measurable disease according to RECIST v1.1 criteria. - Performance status =1 (ECOG). - 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. - Normal cardiac function with a LVEF = 50% by echocardiogram or MUGA. - HBV and HCV serologies must be performed prior to inclusion. 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 PM14 treatment. Cohorts A, B, E, and F: PM14 monotherapy in advanced disease - 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. - A centralized diagnosis of DD liposarcoma or mixoid/hypercellular liposarcoma or leiomyosarcoma must be confirmed for patients in cohort E. - A centralized diagnosis of other sarcomas includes: undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, 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, - Patients must have received a previous chemotherapy line in advanced disease unless contraindicated or not indicated. - Radiological disease progression must be documented within 6 months prior to study entry. - The patient must have been considered eligible for systemic chemotherapy. A maximum of two previous lines for advanced/metastatic disease are allowed. Cohort C: Best scheme of PM14 plus RTP in advanced disease - 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 inclusion to this end. For phase II part, only soft tissue sarcomas will be enrolled. - Patients must have received a previous chemotherapy line in advanced disease. - Disease distribution must allow meeting with normal tissue constrains of radiation therapy. Radiation oncologist must confirm this point at local sites. - Metastatic spread could be present in several organs (i.e. lungs and pelvic fossa) however, not all the loca
Exclusion criteria
Exclusion criteria: Cohorts A, B, E, and F: 1. Performance status = 2 (ECOG). 2. Plasma bilirubin > ULN. 3. Creatinine > 1.6 mg/dL. 4. 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. 5. Patients who do not provide consent for mandatory biological samples (including those required for the translational study) cannot participate in the study. 6. Significant cardiovascular disease (for example, dyspnea > 2 NYHA). 7. 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. 8. Uncontrolled bacterial, mycotic or viral infections. 9. Women who are pregnant or breastfeeding. 10. Psychological, family, social or geographic circumstances that limit the patients’ ability to comply with the protocol or informed consent. 11. Patients participating in another clinical trial or receiving any other investigational product. 12. Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion. 13. Histologies other than those described in the inclusion criteria. Cohort C: 1. Previous treatment with radiotherapy (except if previous radiotherapy treatment plus planned study radiotherapy treatment allow tissue constrains). 2. Performance status = 2 (ECOG). 3. Plasma bilirubin > ULN. 4. Creatinine > 1.6 mg/dL. 5. 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. 6. Severe COPD or other severe pulmonary diseases. 7. Significant cardiovascular disease (for example, dyspnea > 2 NYHA). 8. 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. 9. Patients who do not provide consent for mandatory biological samples (including those required for the translational study) cannot participate in the study. 10. Uncontrolled bacterial, mycotic or viral infections. 11. Women who are pregnant or breastfeeding. 12. Psychological, family, social or geographic circumstances that limit the patients’ ability to comply with the protocol or informed consent. 13. Patients participating in another clinical trial or receiving any other investigational product. 14. Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion. 15. Histologies other than those described in inclusion criteria Cohort D: 1. High-risk localized patients are not allowed to be enrolled (those G3, deep, and larger than 5 cm or those with risk of death at least 40% by sarculator nomogram). 2. Previous treatment with radiotherapy. 3. Primary tumor location other than those indicated in the inclusion criteria. 4. Histological subtypes other than those indicated in the inclusion criteria. 5. Unresectable or inoperable primary tumor. 6. Patients who do not provide consent for mandatory biological samples (including those required for the translational study) cannot participate in the study. 7. Performance status = 2 (ECOG). 8. Plasma bilirubin > ULN. 9. Creatinine > 1.6 mg/dL. 10. History of other cancer with less than 5 years free of diseas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: COHORTS A (24-h IV PM14 in advanced sarcomas) and B (3-h IV PM14 3 consecutive days in advanced sarcomas) Phase I: To determine the maximum tolerated dose (MTD) of PM14 to be used as recommended phase 2 dose (RP2D). COHORTS E (24-h IV PM14 or 3-h IV PM14 3 consecutive days - Expanded to advanced L-sarcomas) and F (24-h IV PM14 or 3-h IV PM14 3 consecutive days - Expanded to other advanced STS: non L-sarcomas) Phase II: To evaluate the progression-free survival rate (PFSR) at 6 months. COHORT C (Best scheme of PM14 plus RTP (3 Gy x 10 days = 30 Gy) in advanced solid tumors: sarcoma, head and neck, and others) Phase I: To determine the MTD of PM14 to be used as RP2D. Phase II: To evaluate the ORR in irradiated nodules only. This objective is considered as a surrogate of palliative relief. COHORT D (Best scheme of PM14 + RTP (1.8 Gy x 25 days = 45 Gy) in localized intermediate sarcoma) Phase I: To determine the MTD of PM14 to be used as RP2D. Phase II: To evaluate the ORR.;Secondary Objective: COHORTS A AND B Phase I: - To evaluate the safety profile. - To evaluate the overall response rate (ORR). - To evaluate the median of progression-free survival (mPFS). - To evaluate quality of life. - To contribute to translational studies. - To characterize the PK of PM14 in the explored regimens COHORTS E AND F Phase II: - To evaluate the overall response rate (ORR). - To evaluate the median of overall survival (mOS). - To evaluate quality of life. - To evaluate the safety profile. - To contribute to translational studies. COHORT C Phase I: - To evaluate the safety profile. - To evaluate the overall response rate (ORR). - To evaluate the median of progression-free survival (mPFS). - To evaluate quality of life. - To contribute to translational studies. Phase II: - To evaluate variations in pain. /- To evaluate variations in analgesic use. (INSUFFICIENT SPACE TO INCLUDE ALL THE INFORMATION. IT IS AVAILABLE IN THE SYNOPSIS.);Primary end point(s): COHORTS | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: - ORR: central radiology review (end of treatment visit, 3 weeks after surgery) - mPFS: 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. - Biological samples for translational study: baseline and cycle 1 day 2 or 3 - mOS: median of time in months from date of enrollment to date of death due to any cause - Changes in pain, in analgesic use and in quality of life: at least measured at baseline, an early assessment 1 week after RT completion, a delayed assessment on days 1 of cycles 2 and 3; and ultra-delayed assessment at 6 months from the first day of treatment. (INSUFFICIENT SPACE TO INCLUDE ALL THE INFORMATION. IT IS AVAILABLE IN THE SYNOPSIS.);Secondary end point(s): 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. • 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). - 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. - Quality of life: Assessed by using the EORTC QLQ-C30 questionnaire. - The clinical study will provide tumor and blood samples for the translational research program. - The clinical study will provide blood samples for the measurement of PM14 concentration and baseline a-1-acid glycoprotein (AAG) levels. COHORTS E AND F Phase II: - Overall response rate (ORR) (according t | — |
Countries
Spain, United States
Contacts
Public ContactGEIS-83 CLINICAL TRIAL INFORMATION
SOFPROMED INVESTIGACIÓN CLÍNICA, SLU
Outcome results
None listed