Neoplasms

All Conditions

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Nutritional and Metabolic Diseases

Rare Diseases

Sarcoma

Ichthyosis, X-Linked

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

The treatment will be administered in 25 daily fractions (Monday-Friday) at the disease site to include the region of suspected micrometastatic spread (Clinical Target Volume 1, CTV1) at a dose of 50 Gy (2Gy

/ fraction) with SIB intensification on volume reduced corresponding to the interface sites between the tumor and the vascular / nerve axes (Clinical Target Volume 2, CTV2) at a dose of 60 Gy (2.4 Gy / fraction). The association with neoadjuvant chemotherapy based on anthracyclines is allowed.

Marta Pacinico

lorenzo livi

lorenzo livi, Dr

Intervention prospective monocentric one arm study on the use of neoadjuvant radiotherapy with simultaneous integrated boost (Simultaneous Integrated Boost, SIB) in patients with STS with indication for preoperative radiotherapy. The treatment will be administered in 25 daily fractions (Monday-Friday) at the disease site to include the region of suspected micrometastatic spread (Clinical Target Volume 1, CTV1) at a dose of 50 Gy (2Gy

/ fraction) with SIB intensification on volume reduced corresponding to the interface sites between the tumor and the vascular / nerve axes (Clinical Target Volume 2, CTV2) at a dose of 60 Gy (2.4 Gy / fraction). The association with neoadjuvant chemotherapy based on anthracyclines is allowed.

Intervention prospective monocentric one arm study on the use of neoadjuvant radiotherapy with simultaneous integrated boost (Simultaneous Integrated Boost, SIB) in patients with STS with indication for preoperative radiotherapy. The treatment will be administered in 25 daily fractions (Monday-Friday) at the disease site to include the region of suspected micrometastatic spread (Clinical Target Volume 1, CTV1) at a dose of 50 Gy (2Gy

/ fraction) with SIB intensification on volume reduced corresponding to the interface sites between the tumor and the vascular / nerve axes (Clinical Target Volume 2, CTV2) at a dose of 60 Gy (2.4 Gy / fraction). The association with neoadjuvant chemotherapy based on anthracyclines is allowed. Objective: The primary objective is to evaluate the benefit of radiotherapy with partial simultaneous integrated boost to the area at risk of incomplete resection in the neoadjuvant treatment of soft tissue sarcoma candidate for conservative surgery. The secondary objectives are to evaluate the outcomes and toxicity Study population: Patients with de novo or locoregional recurrence of STS after surgery.

Estimated enrollment: 33 Inclusion criteria: STS candidate for surgical resection; age \> 18 years Exclusion criteria: previous radiotherapy over the region of interests, inability to express informed consent; planned amputation. Study arm: Intensity Modulated Radiotherapy Study duration: 2 years Enrollment period: 3 years Global study duration: 5 years Current primary outcomes measures: Oncologically negative resection rate (R0 rate) Current secondary outcomes measures: Pathologic Complete Response rate (pCR); Overall Survival (OS); Disease Specific Survival (DSS) Local-Relapse Free Survival (LRFS); Distant-Metastases-Free Survival (DMFS); incidence of acute and late toxicity according to CTCAE v5.0 classification

Sarcoma Preoperative Radiation With Simultaneous INTegrated Boost (SPRINT)

Azienda Ospedaliero-Universitaria Careggi

Professor

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Sirolimus

Temsirolimus

MTOR Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.

Sirolimus Albumin-bound Nanoparticles

Pazopanib hydrochloride

Lee Cranmer, MD

This phase I/II trial studies the side effects and best dose of nab-sirolimus and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nab-sirolimus and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

OUTLINE: This is a phase I, dose-escalation study of nanoparticle albumin-bound rapamycin followed by a phase II study.

Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.

After completion of study treatment, participants are followed up at 30 days, then every 12 weeks.

Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas

A Phase 1/2 Study of Nab-Sirolimus With Pazopanib (VOTRIENT®) in Patients With Advanced Nonadipocytic Soft-Tissue Sarcomas

Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.

A DLT is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-sirolimus and pazopanib. Only toxicities with a clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic AE of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.

A Dose-limiting toxicity is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-Sirolimus or pazopanib. Only toxicities with clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic Ae of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.

Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 where progression is defined as a 20% increase in the sum of the longest diameter of target lesions where the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of new lesions. Will be assessed via descriptive statistics.

Will be based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

Will be assessed using RECIST v1.1. Will be assessed via descriptive statistics.

Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will be assessed via descriptive statistics.

Will be summarized using descriptive statistics.

Will be assessed using descriptive statistics.

Will be based on RECIST v1.1. Will be evaluated by CT imaging.

Will be based on RECIST v1.1evaluated by computed tomography (CT) imaging. Per RECIST V1.1, Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).

Aadi Bioscience, Inc.

University of Washington

Systematic assessment of adverse events is completed by regular investigator assessment.

Participants received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib.

Cohort 1, Dose Level 0

Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib.

Cohort 4, Dose Level -1

Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib.

Cohort 5, Dose Level -2

Participants received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib.

Cohort 6, Dose Level 0B

Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib.

Cohort 9, Dose Level -1B

Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib.

Cohort 10, Dose Level -2B

Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib.

Cohort 11, Dose Level 0C

Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib.

Cohort 12, Dose Level 1C

Participants received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib

Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib

Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib

Participants received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Participants received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Participants received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Total

18-29

30-39

40-49

50-59

60-69

70 and over

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

While the study was originally designed as a phase I/II study, only the phase I component of the study was completed..

Lee Cranmer, MD, PhD

All participants who received at least one dose of ABI-009: either at 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8, 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8, 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8, 30 mg/m\^2 ABI-009 given intravenously on Day 1 only, or 45 mg/m\^2 of ABI-009 given intravenously on Day 1 only.

All Participants

MTD was determined to be ABI-009 on DAY 1 of a 21 day cycle ONLY in combination with daily oral pazopanib.

The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Nab-Rapamycin Dose

All participants who received at least one dose pazopanib: either daily oral 800 mg of pazopanib, or daily oral 400 mg of pazopanib.

The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Pazopanib Dose

Subjects received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib

Subjects received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib

Subjects received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 800 mg of pazopanib

Subjects received 60 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Subjects received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Subjects received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 and Day 8 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Subjects received 30 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Subjects received 45 mg/m\^2 of ABI-009 given intravenously on Day 1 of a 21 day cycle, plus daily oral 400 mg of pazopanib

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

Thrombocytopenia

Neutropenia

WBC decreased, Neutropenia

Lipase elevated

Proteinuria

Thrombocytopenia, Oral mucositis

Thrombocytopenia, Neutropenia

No DLT experienced

Dose Limiting Toxicities

Cohort 11, Dose Level 0C: Participants received 30 mg/m\^2 nab-sirolimus intravenously (IV) on Day 1 only and 400 mg of pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.

Treatment (ABI-009, Pazopanib)

Three patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle, with 400 mg of oral daily pazopanib.

Progression-free Survival (PFS) Rate (Phase II)

Incidence of Adverse Events Profile (Phase I and II)

Three patients were treated at the recommended Phase II dose of 30 mg/m\^2 nab-sirolimus intravenously on Day 1 of a 21-day cycle with 400 mg of oral daily pazopanib.

Median PFS (Phase II)

Progression-Free Survival Rate (Phase II)

Median Overall Survival (OS) (Phase II)

Overall Survival (Phase II)

Objective Response Rate (CR + PR) (Phase II)

Disease Control Rate (Complete Response [CR] + Partial Response [PR] + Stable Disease [SD]) (Phase II)

Duration of Response (Phase II)

Overall Study

Participants will receive up to 3.2 mg/m\^2 of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity and trunk sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Participants will receive up to 3.2 mg/m\^2 of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity myxoid Liposarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Participants will receive up to 3.2 mg/m\^2 of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 6 weeks of pre-operative conventional external beam radiation therapy given as 45-50.4 Gy delivered over 25-28 fractions starting on cycle 1 for participants with retroperitoneal sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Participants will receive the maximum tolerated dose of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity and trunk sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Participants will receive the maximum tolerated dose of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 2 weeks of pre-operative radiation given as 35 Gy in 5 fractions (gross tumor volume (GTV)) with fractions administered at least every other day starting on cycle 2 for participants with extremity myxoid Liposarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Participants will receive the maximum tolerated dose of neoadjuvant lurbinectedin IV once every cycle (a cycle is 21 days) in combination with 6 weeks of pre-operative conventional external beam radiation therapy given as 45-50.4 Gy delivered over 25-28 fractions starting on cycle 1 for participants with retroperitoneal sarcoma. Non-investigational surgery will take place 4-6 weeks after completion of radiation therapy. Participants with metastatic disease at the time of study enrollment may be able to continue study treatment for 2 years from the time of initiating treatment. Participants with localized disease at the time of study enrollment may continue study treatment for approximately 3 months AND then be followed on-study surveillance.

Lurbinectedin

Conventionally fractionated radiotherapy or external beam radiation

Radiotherapy

Non-investigational surgical procedure on tumor tissue

Non-investigational surgery

Lisa Tan

Varun Monga, MD

Steve Braunstein, MD, PhD

Mohammed Milhem, MD

This is a multi-center, multi-arm open-label phase Ib/II clinical study assessing the efficacy of concurrent lurbinectedin in combination with radiotherapy in patients with locally advanced, resectable, high-grade sarcomas.

PRIMARY OBJECTIVES:

Phase Ib:

I. To determine the safety and tolerability of neoadjuvant lurbinectedin

* in combination with preoperative 2 weeks of hypofractionated radiation for extremity and trunk sarcoma, or
* with 6 weeks of conventionally fractionated radiation for retroperitoneal sarcoma II. To determine the maximum tolerated dose (MTD) for neoadjuvant lurbinectedin in combination with preoperative external beam radiation therapy (EBRT) in patients with sarcoma.

Phase II:

I. To estimate the efficacy of neoadjuvant lurbinectedin in combination with preoperative EBRT (hypofractionated or conventionally fractionated), according to endpoint defined by sarcoma type and location:

* Cohort 1: extremity and trunk sarcoma (HFRT)
* Cohort 2: Extremity myxoid liposarcoma (HFRT)
* Cohort 3: Retroperitoneal sarcoma (CFRT course)

SECONDARY OBJECTIVES:

I. Time to disease progression (local or distant recurrence).

II. Overall response rate (ORR) pre-operative as measured by RECIST 1.1 or a later tool for monitoring disease progression.

III. Overall survival.

IV. To grade radiation related skin toxicity overlying the tumor area.

V. To determine long term major wound healing complications with the use of this combination in all cohorts.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in monocyte, macrophage, T cell, and RNA expression levels over time.

OUTLINE:

Participants will receive neoadjuvant lurbinectedin concurrent with radiation therapy. Non-investigational surgery will be performed 4-6 weeks from the end of radiation therapy. Participants with localized disease at the time of study enrollment will be on surveillance on-study for 2 years. Post-operatively participants will be followed every 12 +/- 4 weeks for approximately 2 years from the end of treatment. Participants with known metastatic disease will be followed until progression, toxicity and thereafter for 2 years.

Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas

Phase 1b/2 Trial Using Neoadjuvant Lurbinectedin With Concurrent Preoperative Radiation in Patients With Locally Advanced Soft Tissue Sarcomas of Extremity, Trunk, and Retroperitoneum

The proportion of participants with reported DLTs will be reported for

MTD is defined as the highest dose at which no more than one instance of dose limiting toxicity (DLT) is observed among 1 of 6 participants treated.

Pathological necrosis rate, defined as the proportion of participants with \>=95% pathological necrosis.

Local control rate is defined as the proportion of participants with \>=50% of the resected sample showing any histological treatment effect.

Overall response rate is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Time to progression is defined as the time from first day of study treatment to first documented occurrence of disease progression (including local and distant recurrences). Participants without progression will be censored at their last disease evaluation will be reported.

The proportion of pre-operative participants with a confirmed CR or PR as measured by RECIST 1.1 or a later tool for monitoring disease progression will be reported.

The median overall survival time is defined as the time from first day of study treatment to death due to any cause will be reported. Participants who are still alive will be censored at their last date known to be alive.

Incidence of radiation related skin toxicity by grade as classified by the NCI CTCAE version 5.0 and additionally assessed by radiation oncologists will be reported.

The proportion of participants requiring secondary operation under general or regional anesthesia for wound repair, invasive procedure without general or regional anesthesia (mainly aspiration of seroma), readmission for wound care such as intravenous antibiotics, or persistent deep packing for 120 days (4 months) or longer will be reported.

Jazz Pharmaceuticals

University of California, San Francisco

Doxorubicin

Liposomal doxorubicin

300 mg/m2 of TH-302 will be administered by IV infusion over 30-60 minutes on Days 1 and 8 of a 21-day cycle.

Doxorubicin may be delivered as a bolus administration or as a continuous infusion administration; administration schedule must be specified prior to enrollment.

Doxorubicin bolus administration: 75 mg/m2 administered by bolus injection starting on Day 1 of a 21-day cycle.

Doxorubicin continuous administration: 75 mg/m2 administered by continuous IV infusion over 48-96 hours starting on Day 1 of a 21-day cycle.

Doxorubicin administration will start between 2 to 4 hours after completion of the TH-302 infusion when used in combination with TH-302.

TH-302 in Combination with Doxorubicin

Doxorubicin may be delivered as a bolus administration or as a continuous infusion administration; administration schedule must be specified prior to enrollment.

Doxorubicin bolus administration: 75 mg/m2 administered by bolus injection starting on Day 1 of a 21-day cycle.

Doxorubicin continuous administration: 75 mg/m2 administered by continuous IV infusion over 48-96 hours starting on Day 1 of a 21-day cycle.

William Tap, MD

The purpose of this study is to determine whether TH-302 in combination with Doxorubicin is safe and effective in the treatment of Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma.

TH-302 is designed to target the hypoxic regions of tumors which are generally located distant from tumor vessels. Doxorubicin has poor tissue penetration and targets the regions of tumors that are located in proximity to the tumor vessels. The presence of hypoxia in solid tumors is associated with a more malignant phenotype and resistance to chemotherapy. The hypoxia-activated prodrug, TH-302, is designed to selectively target the hypoxic microenvironment. Soft tissue sarcomas have evidence supporting the presence of hypoxia based on pO2 histography, F-MISO and gene expression profiling. There is an absence of therapeutic options for subjects with soft tissue sarcoma. Combining doxorubicin with TH-302 may enable the targeting of both the normoxic and hypoxic regions of soft tissue sarcoma.

A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

A Randomized Phase 3, Multicenter, Open-Label Study Comparing TH-302 in Combination With Doxorubicin vs. Doxorubicin Alone in Subjects With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma

Efficacy will be determined by overall survival in subjects with locally advanced unresectable or metastatic soft tissue sarcoma previously untreated with chemotherapy compared with doxorubicin alone

To investigate the pharmacokinetics of TH-302, Br-IPM, doxorubicin, and doxorubicinol in plasma

Sarcoma Alliance for Research through Collaboration (SARC)

Threshold Pharmaceuticals

Symptoms and General Pathology

Recurrence

Disease Attributes

Irinotecan

CEB-01 is a polymeric drug with a delivery system loaded with SN-38, and will be placed in the surgical bed at the time of tumor resection.

CEB-01 membrane loaded with SN-38

Ana Sebio, M.D. Ph.D.

This is an open label, first-in-man clinical trial to assess safety and tolerability of CEB-01 PLGA membrane in patients with recurrent or locally advanced retroperitoneal soft tissue sarcoma after surgery.

The trial will be conducted in 3 dose-escalation cohorts (3 patients each, enrolling patients one by one, after 4 weeks of observation and agreement of Scientific Committee and DMC) and in an expansion cohort, using the highest safe and tolerable dose. The study will follow a 3+3 modified design; dose escalation will follow a modified Fibonacci method. CEB-01 carrying a SN-38 dose between 9 and 36 mg will be placed in the surgical bed at the time of tumor resection.

CEB-01 is a poly(lactic-co-glycolic acid) (PLGA) polymeric drug with a delivery system loaded with SN-38, and will be placed in the surgical bed at the time of tumor resection.

CEB-01 carrying a SN-38 dose between 9 and 36 mg will be administered. CEB-01 will be placed on all surfaces that were in contact with and/or were infiltrated by the tumor.

Confirmatory central reviewing of diagnosis will be performed for all patients, using tumor samples obtained during surgery; additionally, patients will also be included according to local Pathological Anatomy (PA) diagnosis.

Patients will be followed-up once every week during the first 8 weeks of the study, and then every 2 weeks up to 12 weeks after implantation of CEB-01. Thereafter, follow-up schedule will be as per normal practice until study completion.

Efficacy assessment will be performed by Magnetic Resonance Imaging (MRI) \[Computed tomography (CT) scan and Positron Emission Tomography (PET-CT) are also allowed\] according to RECIST 1.1 criteria. Baseline image determination will be performed at week 12 (±3 days) after surgery; if the image analysis is not conclusive due to wound healing in the tumor bed, it will be repeated on week 16 (±3 days) post-surgery, and every 12 weeks thereafter.

A pharmacokinetic assessment of SN-38 will be performed in all patients, and the Cmax, Tmax, half-life, and area under the time-drug concentration curve (AUC) of the drug will be determined. Blood samples will be collected at baseline and at 8 time points after CEB-01 implantation.

Assessment of adverse events, safety, and toxicity will be performed according to the Common Terminology Criteria for Adverse Events (CTCAE - version 5.0) at each patient visit from the time of Informed Consent until the end of the study.

Quality of Life based on EORTC Quality of Life Questionnaire (QLQ) 30 will be measured prior surgery, at month 1 and month 3.

This is an open label, first-in-human clinical trial that will be conducted in 3 dose-escalation cohorts (3-6 patients each) and in an expansion cohort, at the highest dose determined to be safe and tolerable.

CEB-01 loaded with a SN-38 dose between 9 and 36 mg will be allocated to each patient.

First-in-man Clinical Trial of CEB-01 PLGA Membrane in Recurrent or Locally Advanced Retroperitoneal Soft Tissue Sarcoma

First-in-man Clinical Trial to Assess Safety and Tolerability of CEB-01 PLGA Membrane in Patients With Recurrent or Locally Advanced Retroperitoneal Soft Tissue Sarcoma After Surgery

The number of patients experiencing dose limiting toxicities during the Dose Limiting Toxicities (DLT) observation period of 2 weeks.

Frequency of adverse events reported classified by type and severity.

Frequency of treatment related adverse events reported classified by type and severity.

Time from the start of treatment to the date of local relapse according to the RECIST 1.1 criteria, or death due to any cause. Those patients who are alive and have not relapsed at the last follow-up, will be censored at the date of the last follow-up.

Relapse definition: For patients in which R0 is obtained by surgery, relapsed should be considered when disease reappears with size \> 1 cm (measurable disease). For patients with R1 or R2, RECIST 1.1 guideline should be used for disease progression definition.

Time from the start of treatment to the date of the first progression according to the RECIST 1.1 criteria, or death due to any cause. Those patients who are alive and have not progressed at the last follow-up, date of progression will be censored at the date of the last follow-up.

Median of overall survival. Time from the start of the trial treatment to the date of exitus for any cause. In those patients who are alive at the last follow-up, OS will be censored by the date of the last follow-up in which the patient was alive.

Questionnaire developed and validated to assess the quality of life of cancer patients.

CEBIOTEX

INNO-206 administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously (IV) on Day 1 every 21 days for up to 6 consecutive cycles

INNO-206

Doxorubicin administered at 75 mg/m2 for up to 6 consecutive cycles.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sarcoma Preoperative Radiation With Simultaneous INTegrated Boost (SPRINT)	NCT05761054	Soft Tissue Sar...	RT	18 Years -	Azienda Ospedaliero-Universitaria Careggi
Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas	NCT03660930	Advanced Soft T... Locally Advance... Metastatic Soft...	Sirolimus Album... Pazopanib hydro...	18 Years -	University of Washington
Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas	NCT06217536	Locally Advance...	Lurbinectedin Radiotherapy Non-investigati...	18 Years -	University of California, San Francisco
A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma	NCT01440088	Soft Tissue Sar...	TH-302 in Combi... Doxorubicin	15 Years -	Threshold Pharmaceuticals
First-in-man Clinical Trial of CEB-01 PLGA Membrane in Recurrent or Locally Advanced Retroperitoneal Soft Tissue Sarcoma	NCT04619056	Locally Advance... Recurrent Soft ...	CEB-01 membrane...	18 Years -	CEBIOTEX
Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma	NCT01514188	Metastatic Soft... Locally Advance... Unresectable So...	INNO-206 Doxorubicin	15 Years - 80 Years	ImmunityBio, Inc.
Neoadjuvant Lurbinectedin and Preoperative Radiation for Treating Soft Tissue Sarcomas	NCT06217536	Locally Advance...	Lurbinectedin Radiotherapy Non-investigati...	18 Years -	University of California, San Francisco
Nivolumab With or Without Ipilimumab in Treating Patients With Metastatic Sarcoma That Cannot Be Removed by Surgery	NCT02500797	Locally Advance... Locally Advance... Locally Advance... Locally Advance... Metastatic Bone... Metastatic Lipo... Metastatic Soft... Metastatic Undi... Metastatic Unre... Pleomorphic Lip... Stage III Bone ... Stage III Soft ... Stage IV Bone S... Stage IV Soft T... Stage IVA Bone ... Stage IVB Bone ... Unresectable Bo... Unresectable De... Unresectable Li... Unresectable Ma... Unresectable So...	Ipilimumab Laboratory Biom... Nivolumab Quality-of-Life...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for locally advanced soft tissue sarcoma