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

Liposarcoma

Histiocytoma, Malignant Fibrous

Leiomyosarcoma

Undifferentiated Pleomorphic Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Olaratumab

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

75 milligrams per meter squared (mg/m\^2) doxorubicin administered intravenously (IV) on day 1 of each 21-day cycle for 8 cycles plus 20 milligrams per kilogram (mg/kg) dose of olaratumab administered IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab administered IV on day 1 and day 8 of cycles 2-8. Beginning with cycle 9, 15 mg/kg olaratumab administered IV on day 1 and day 8 of each subsequent 21-day cycle until documented progressive disease (PD) or discontinuation for any other reason.

75 mg/m\^2 doxorubicin administered IV on day 1 of each 21-day cycle for 8 cycles plus placebo (equivalent volume) administered IV on day 1 and day 8 for 8 cycles. Beginning with cycle 9, placebo (equivalent volume) administered on days 1 and 8 of each subsequent 21-day cycle until PD or discontinuation for any other reason.

Placebo

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The main purpose of this study is to evaluate the efficacy of the combination of doxorubicin plus the study drug known as olaratumab versus doxorubicin plus placebo in participants with advanced or metastatic soft tissue sarcoma.

A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Doxorubicin Plus Olaratumab Versus Doxorubicin Plus Placebo in Patients With Advanced or Metastatic Soft Tissue Sarcoma

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Overall survival was defined as the time from the date of randomization to the date of death due to any cause. For each participant, prior to data analysis, a reasonable effort was made to obtain the most up-to-date status (date of death or last date known to be alive). For any participant not known to have died as of the data cutoff date, OS was censored at the date the participant was last known to be alive. For any participant who withdrew consent for survival follow-up, OS was censored at the last date for which the participant provided consent for follow-up contact. The Kaplan-Meier method was used to estimate median parameters.

PFS was defined by (Response Evaluation Criteria In Solid Tumors RECIST v.1.1) as the time from the date of randomization to the first date of radiologic disease progression or death due to any cause. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus absolute increase of at least 5 millimeter (mm), or unequivocal progression of non-target lesions, or 1 or more new lesions. Censoring for death or PD due to increase sum of target lesions is defined for each participant as the time from the date of randomization to the first date of radiographic documentation of 1 or more lesions. Censoring for death without progression is defined as the date of death if there is no prior or concurrent radiologic disease progression.

ORR was defined as the percentage of participants achieving a best overall response of complete response (CR) + partial response (PR). CR is the disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. Best overall response is classified based on the overall responses assessed by study investigators according to RECIST v1.1.

DCR was defined as the percentage of randomized participants achieving a best overall response of CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PD is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time to first worsening was calculated as the time from the first study drug dose to the first observation of worsening according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 total items covered by 1 of 3 dimensions (1 global health status/QoL total score, 5 functional subscales \[physical, role, cognitive, emotional, and social\]), and 9 symptom subscales \[fatigue/nausea/vomiting/pain/dyspnea/insomnia/appetite loss/constipation/diarrhea\]). There are 28 questions answered on a 4-point scale where 1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best). A linear transformation was used to obtain total score ranging from 0 to 100 where "worsening" was defined as an increase of at least 10 points for the symptom scales or a decrease of at least 10 points for the functional scales and the global health status/QoL scale.

The EQ-5D-5L is a standardized measure of health status used to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of a descriptive system of the respondent's health which comprises the following 5 dimensions: (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Health status was calculated from a set of item weights to derive a score of 0 to 1, with 1 representing the best health status. United Kingdom (UK) weights were applied. The analysis includes all cycles for which at least 25% of participants in each arm have an assessment. For each participant a change from baseline was calculated for every post-baseline assessment by subtracting the baseline assessment result from the current assessment result. Maximum improvement (over baseline) was determined from the set of all post-baseline change scores.

Time to first worsening of the brief pain inventory short form modified (mBPI-sf) "worst pain score" was defined as the time from the date of the first study drug dose (baseline date) to the first date of a "worst pain" score increase of greater than or equal to (≥) 2 points from baseline. The mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes).

The duration of overall response was defined for each participant with a best response of CR or PR and measured from the time measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that disease is recurrent or objective disease progression or death due to any cause is observed (taking as reference for PD the smallest measurements recorded on study).

Duration of disease control was defined for each participant with a best response of CR, PR, or stable disease (SD) as the time from randomization to the first date of disease progression or death due to any cause.

The PK systemic clearance parameter estimates from the current analysis are listed together with the population PK model estimates.

The PK parameter estimates from the current analysis are listed together with the population PK model estimates. The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2).

Eli Lilly and Company

All randomized participants who received at least one dose of study drug.

75 milligrams per meter squared (mg/m\^2) doxorubicin administered intravenously (IV) on day 1 of each 21 day cycle for 8 cycles plus 20 milligrams per kilogram (mg/kg) dose of olaratumab administered IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab administered IV on day 1 and day 8 of cycles 2-8. Beginning with cycle 9, 15 mg/kg olaratumab administered IV on day 1 and day 8 of each subsequent 21 day cycle until documented progressive disease (PD) or discontinuation for any other reason.

Doxorubicin + Olaratumab

75 mg/m\^2 doxorubicin administered IV on day 1 of each 21 day cycle for 8 cycles plus placebo (equivalent volume) administered IV on day 1 and day 8 for 8 cycles. Beginning with cycle 9, placebo (equivalent volume) administered on days 1 and 8 of each subsequent 21 day cycle until PD or discontinuation for any other reason.

Doxorubicin + Placebo

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Russia

Austria

South Korea

Netherlands

Sweden

Brazil

Poland

France

Argentina

Hungary

Japan

United Kingdom

Switzerland

Spain

Canada

Belgium

Finland

Taiwan

Denmark

Italy

Mexico

Israel

Australia

Germany

Region of Enrollment

Chief Medical Officer

All randomized participants. Censored participants in Doxorubicin + Olaratumab arm = 87 and Doxorubicin + Placebo arm = 91

Overall Survival (OS)

All randomized participants with LMS. Censored participants in Doxorubicin + Olaratumab arm = 42 and Doxorubicin + Placebo arm = 40.

Overall Survival (OS) Leiomyosarcoma (LMS)

All randomized participants. Censored participants in the Doxorubicin + Olaratumab arm = 39 and the Doxorubicin + Placebo arm =34.

Progression Free Survival (PFS)

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

Global Health Status/QoL

Role Functional Scale

Physical Functional Scale

Emotional Functional Scale

Cognitive Functional Scale

Social Functional Scale

Fatigue Symptom Scale

Nausea and Vomiting Symptom Scale

Pain Symptom Scale

Dyspnea Symptom Scale

Insomnia Symptom Scale

Appetite Loss Symptom Scale

Financial Difficulties Scale

Constipation Symptom Scale

Diarrhea Symptom Scale

All randomized participants who completed at least 1 baseline assessment and at least 1 subsequent assessment during the study period.

Time to First Worsening on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores

All randomized participants who had a baseline and a post-baseline measurement.

Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L)

Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"

All randomized participants who have evaluable DoR data.

Duration of Overall Response (DoR)

All randomized participants who had evaluable DDC data.

Duration of Disease Control (DDC)

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate

All randomized participants who had received at least one dose of study drug and had evaluable PK data.

PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate

75 milligrams per meter squared (mg/m\^2) doxorubicin administered intravenously (IV) on day 1 of each 21 day cycle up to 8 cycles plus 20 milligrams per kilogram (mg/kg) dose of olaratumab administered IV on day 1 and day 8 of cycle 1 and 15 mg/kg olaratumab administered IV on day 1 and day 8 of cycles 2-8. 15 mg/kg olaratumab administered IV on day 1 and day 8 of each subsequent 21 day cycle thereafter until documented progressive disease (PD) or discontinuation for any other reason.

75 mg/m\^2 doxorubicin administered IV on day 1 of each 21 day cycle up to 8 cycles plus placebo (equivalent volume) administered IV on day 1 and day 8 for 8 cycles. Placebo (equivalent volume) administered on days 1 and 8 of each subsequent 21 day cycle thereafter until PD or discontinuation for any other reason.

Overall Study

Immune System Diseases

Blood and Lymph Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Behaviors and Mental Disorders

Mastocytosis

Leukemia

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Renal Insufficiency

Glioma

Lung Neoplasms

Gastrointestinal Stromal Tumors

Aggression

Mastocytosis, Systemic

Mast Cell Activation Disorders

Leukemia, Mast-Cell

Neoplasms, Connective Tissue

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Germ Cells Tumors

Penile Cancer

Systemic Mastocytosis

Escalation Phase: DCC-2618 tablets in escalating dose cohorts given orally BID (twice daily) every 12 hours or once daily (QD) for repeated 28-day cycles. Participants may continue to receive study drug until discontinuation criteria are met. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 3 prior therapies. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received 4 prior therapies. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST who have received at least one prior therapy and no more than 2 prior therapies. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with systemic mastocytosis and other hematologic malignancies.\[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with malignant gliomas.\[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with other solid tumors. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with melanomas. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with soft tissue sarcomas.\[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with germ cell, penile cancer and non-small cell lung carcinoma (NSCLC). \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles in patients with GIST and other solid tumors with renal impairment. \[Closed for Enrollment\]

150 mg DCC-2618 given once daily in repeated 28-day cycles for active patients from the Escalation and Extension Phases.

DCC-2618

Deciphera Pharmaceuticals, LLC

This is a Phase 1, open-label, first-in-human (FIH) dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of DCC-2618, administered orally (PO), in adult patients with advanced malignancies. The study consists of 2 parts, a dose-escalation phase, and an expansion phase. All active patients (from both dose-escalation and expansion phases) will then transition into an extension phase.

A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies

A Multicenter Phase 1, Open-Label Study of DCC-2618 to Assess Safety, Tolerability, Efficacy, and Pharmacokinetics in Patients With Advanced Malignancies

Dose limiting toxicities, AEs, SAEs, discontinuation of drug due to toxicity, physical exams and ECOG PS, ophthalmologic examinations, changes from baseline in laboratory parameters, electrocardiograms, LVEF, and vital signs.

Objective response rate (ORR); Disease control rate (DCR)

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
A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma	NCT02451943	Soft Tissue Sar...	Olaratumab Doxorubicin Placebo	18 Years -	Eli Lilly and Company
A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies	NCT02571036	Gastrointestina... Advanced System... Advanced Cancer...	DCC-2618 DCC-2618	18 Years -	Deciphera Pharmaceuticals LLC
A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma	NCT02451943	Soft Tissue Sar...	Olaratumab Doxorubicin Placebo	18 Years -	Eli Lilly and Company
A Safety, Tolerability and PK Study of DCC-2618 in Patients With Advanced Malignancies	NCT02571036	Gastrointestina... Advanced System... Advanced Cancer...	DCC-2618 DCC-2618	18 Years -	Deciphera Pharmaceuticals LLC

Spots Global Cancer Trial Database for soft tissue sarcoma (sts)