Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Liposarcoma

Chondrosarcoma

Leiomyosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Neoplasms, Adipose Tissue

Neoplasms, Connective Tissue

Retroperitoneal Liposarcoma

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Doxorubicin

Liposomal doxorubicin

Nilotinib

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

The nilotinib-adriamycin combination will be given in 4 cycles of 21 days. In each cycle, nilotinib will be administered at fixed dose of 400 mg/12h orally during 6 consecutive days (1-6) and endovenous adriamycin (20 minutes) on day 5 at three levels (in phase I, dosage of 60 mg/m2, 65 mg/m2, and 75 mg/m2 will be tested to determine the recommended dose for phase II).

Nilotinib-adriamycin

Patricio J. Ledesma, BEng

Santiago Blasco, BSc

Javier Martín, MD, PhD

Ignacio Delgado, MD

Olatz Etxaniz, MD

Antonio López-Pousa, MD

Claudia Valverde, MD

Ramón de las Peñas, MD

Josefina Cruz, MD

Luis Miguel de Sande, MD

Ricardo Cubedo, MD

Andrés Redondo, MD

Mª Ángeles Vaz, MD

Jerónimo Martínez, MD

Nuria Láinez, MD

Ana de Juan, MD

Yolanda Vidal, MD

Pilar Sancho, MD

Javier Medina, MD

Javier Lavernia, MD

Juan Antonio Carrasco, MD

Javier Martínez-Trufero, MD

Phase I/II multicenter and prospective trial of nilotinib and adriamycin as neoadjuvant treatment in liposarcomas and leiomyosarcomas of retroperitoneum.

The main objective of this study is to improve relapse-free survival (RFS)and overall survival (OS) decreasing from 50% to 30% the relapse percentage at 5 years in patients with resected sarcoma of retroperitoneum.

Secondary objectives include the analysis of antitumoral activity through response rate (RECIST and tissular changes), the assessment of positive correlation between biomarkers and clinical results, the study of long term overall survival, and the analysis of the safety profile of the nilotinib-adriamycin combination.

The trial hypothesis is that the nilotinib-adriamycin combination is synergistic and therefore better response results are expected (from 20% as P0 to 40% as P1). The study seeks to find a positive correlation between biomarkers and clinical results in retroperitoneal liposarcoma and leiomyosarcoma treated with the mentioned combination.

The study involves the participation of 20 hospitals of the Spanish Sarcoma Group (GEIS). The treatment consists of 4 neoadjuvant cycles of nilotinib-adriamycin on patients with resectable retroperitoneal sarcoma. The research comprises a robust translational study as well as histological and radiological reviews.

The nilotinib-adriamycin combination will be given in 4 cycles of 21 days. In each cycle, nilotinib will be administered at fixed dose of 400 mg/12h orally during 6 consecutive days (1-6) and endovenous adriamycin (20 minutes) on day 5 at three levels (in phase I, dosage of 60 mg/m2, 65 mg/m2, and 75 mg/m2 will be tested to determine the recommended dose for phase II).

Phase I includes patients with retroperitoneal liposarcoma, retroperitoneal leiomyosarcoma and chondrosarcoma. Phase II is focused on retroperitoneal liposarcoma and leiomyosarcoma only.

Trial of Nilotinib and Adriamycin as Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum

GEIS-27: Phase I/II Multicenter and Prospective Trial of Nilotinib and Adriamycin as Neoadjuvant Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum

The main goal of the study is to improve relapse-free survival (RFS) and overall survival (OS) decreasing from 50% to 30% the percentage of relapse at 5 years in patients with resected retroperitoneal sarcoma.

To determine the objective response rate (ORR) (confirmed complete response \[CR\] and partial response \[PR\]) using RECIST 1.1 criteria

Overall survival measured from treatment start date until date of death, whichever the cause, assessed up to 100 months

Number and type of adverse events according to CTCAE 4.0

Broto, Javier Martín, M.D.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Wilms Tumor

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Syndrome

Neoplastic Syndromes, Hereditary

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Genetic Diseases, Inborn

Wilms' Tumor

Favorable Histology Stage I \& II and FH Stage III/IV Delayed Local Control with clear surgical margins and pathologically negative lymph nodes. Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT.

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT

The treatment approach with radiation therapy prescribed in this trial is designed to deliver highly conformal radiation therapy (proton beam radiation or intensity modulated photon radiation) to target volumes that are based on the burden of disease.

Proton Beam Radiation (PBRT)

Patients will receive standard of care chemotherapy based on diagnosis and stage.

DD-4A Chemotherapy Regimen

Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy

Complete Surgical Resection

Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy.

Surgical Resection

Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy.

Partial Nephrectomy

Matthew J Krasin, MD

Participants are being asked to take part in this clinical trial, a type of research study, because the participants have a Wilms Tumor cancer.

Primary Objectives

To determine whether delivery of proton beam radiation to a conformal reduced target volume in the flank allows normal flank growth compared to the contralateral untreated side and non-irradiated patients.

Secondary Objectives

To deliver proton beam radiation to a conformal reduced target volume (partial kidney proton beam radiation therapy) in the affected kidney(s) for patients with Stage V (bilateral Wilms tumor) and specific involved surgical margins yielding no reduction in the high control rates seen with more traditional flank / whole kidney fields.

Exploratory Objectives

* Study the feasibility of sparing the residual kidney, spine and liver in patients requiring whole abdomen radiation therapy using either a proton beam treatment technique or intensity-modulated radiation therapy ( IMRT) photon based technique.
* Study the feasibility of delivering whole lung radiation therapy with proton beams with the goals of sparing the developing breast tissue, heart structures, thyroid and liver.
* Develop simultaneous xenografts and organoid models from the same starting material to study Wilms tumor biology and compare responses to chemotherapeutic agents.
* Define the evolution of organ specific (kidney, liver, pancreas, etc.) abnormalities (laboratory studies) as an early marker of possible late end organ damage and their relationship to radiation.
* Study and evaluate impact of proton therapy on the musculoskeletal system and physical performance and compare with photon therapy cases treated with classical treatment fields.
* Assess CTC-AE and Pediatric Patient Reported Outcomes during radiation and in follow-up, correlating with disease, treatment and patient variables.
* Correlate quantitative MRI values, including apparent diffusion coefficient (ADC) values, with histopathology findings post-surgery in children with (bilateral) Wilms.
* Assess daily variations in proton range along each treatment beam using standard pre-treatment cone beam CT or on-treatment MR.

Participants will receive proton beam radiation therapy (PBRT) according to stage and surgical findings.

Favorable Histology Stage I \& II and FH Stage III/IV Delayed Local Control with clear surgical margins and pathologically negative lymph nodes: Participants will undergo complete surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. PBRT will not be administered to the primary site in those with no evidence of spill, peritoneal involvement, lymph node (LN) involvement or microscopic residual in the abdomen. Systemic therapy will be delivered in a standard of care manner according to histology and stage.

Stage III \& IV Adjuvant RT: Participants will undergo surgical resection at diagnosis or after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT. Systemic therapy will be delivered in a standard of care manner according to histology and stage.

Stage V Adjuvant RT: Participants will undergo partial nephrectomy after 6-12 weeks of induction chemotherapy. Those with evidence of LN involvement, surgical margin involvement, local or diffuse spill, gross disease in the renal bed or peritoneal implants, will receive adjuvant PBRT. Systemic therapy will be delivered in a standard of care manner according to histology and stage.

Systemic therapy will follow a well-defined standard of care based on Children's Oncology Group (COG) approaches including pre-operative chemotherapy and adjuvant chemotherapy. The intent will be to standardize chemotherapy to ensure a consistent background of standard of care therapy, while not mandating additional data collection beyond the specific trial objectives.

Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation

Multi-Center Trial Sponsored by St. Jude Children's Research Hospital for the Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Half circumference measurement at 3 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

Half circumference measurement at 5 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

Half circumference measurement at 7 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

Half circumference measurement at 10 year from irradiated and unirradiated hemi-abdomen for patients in need of flank radiation

This objective is to investigate whether deliver proton beam radiation to a conformal reduced target volume (partial kidney proton beam radiation therapy) in the affected kidney(s) for patients Stage V (bilateral Wilms tumor) with specific involved surgical margins yielding no reduction in the high control rates seen with more traditional flank / whole kidney fields.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Nilotinib and Adriamycin as Treatment in Liposarcomas and Leiomyosarcomas of Retroperitoneum	NCT02587169	Retroperitoneal... Retroperitoneal... Chondrosarcoma	Nilotinib-adria...	18 Years - 70 Years	Broto, Javier Martín, M.D.
Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation	NCT04968990	Wilms Tumor	Proton Beam Rad... DD-4A Chemother... Complete Surgic... Surgical Resect... Partial Nephrec...	-	St. Jude Children's Research Hospital
Treatment of Newly Diagnosed Patient's With Wilm's Tumor Requiring Abdominal Radiation Delivered With Proton Beam Irradiation	NCT04968990	Wilms Tumor	Proton Beam Rad... DD-4A Chemother... Complete Surgic... Surgical Resect... Partial Nephrec...	-	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for retroperitoneum