Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

RAD001 was administered orally as once daily dose of 10 mg PO daily x 2 weeks (14 X 10 mg tablets) continuously from study day 1 until the end of therapy (2 weeks later) or unacceptable toxicity.

Patients were instructed to take RAD001 in the morning, at the same time each day.

RAD001

Jonathan S. Zager, M.D.

The goal of this clinical research study is to learn if the study drug RAD001 can stop or slow the growth of resectable soft tissue sarcoma. The patient's physical state, their symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study will help the research team decide if RAD001 is safe and effective in patients with this condition. The study drug, RAD001, is made by Novartis Pharmaceuticals Corporation.

A single-arm, open label, proof of principle phase II study exploring the efficacy of RAD001 in resectable soft tissue sarcomas either in the extremities, trunk or retroperitoneum. Patients with resectable sarcomas as detailed below were to have a core biopsy for molecular markers prior to therapy with RAD001 10mg PO daily x 2 weeks. Within 7-14 days of the end of therapy with RAD001, the patients were to be brought to surgery for definitive resection or, should they be candidates for neoadjuvant radiation, would have 6 16 gauge core biopsies taken percutaneously or using image guidance. Pharmacodynamic markers as detailed in the objectives were to be assessed in the laboratory.

Patients were to be numbered sequentially from 1 to 40, or more if there were patients that dropped out due to drug toxicity, with the goal of achieving 40 patients in accrual for evaluation of the pre- and post-treatment tumor samples for Pharmacodynamic assays.

Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas

A Single-arm, Open Label Phase II Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas

PD markers of RAD001 on downstream signaling pathways in patients with sarcomas: p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA by Western blot, quantitative multiplex assays and immunohistochemical studies measured pre and post the 2 week treatment of RAD001. Patients were to be separated into two groups, responders and non responders based on PD results and downstream up regulation of the referenced pathways. Mean fractional inhibition of each PD marker for the responding and non-responding groups were to be calculated. Our planned analysis was for 40 participants.

Quantitative in vivo and ex vivo assessments of PD markers (p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA) were to be normalized within the same sample. The extent of inhibition is defined as the fractional inhibition in each patient calculated as \[(PreRx normalized PD marker - PostRx normalized PD marker) / PreRx normalized PD marker\] x 100. Same definition would apply to each of these markers. Our planned analysis was for 40 participants.

We planned to determine pathological response in terms of tumor necrosis and apoptosis assessed on the resected specimens after 2 weeks of RAD001 therapy. Percent necrosis was to be reported based on the routine H and E staining. In addition to cleaved PARP analysis, TUNEL assays were to be performed judging the amount of apoptosis in the specimens after treatment. Our planned analysis was for 40 participants.

Memory CD8 T cell enhanced production as determined by fluorescence activated cell sorter (FACS) analysis on blood and tumor core biopsy specimens taken before and after therapy with RAD001. Our planned analysis was for 40 participants.

Novartis

H. Lee Moffitt Cancer Center and Research Institute

RAD001 Administration

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

This study was terminated early due to sponsor budget cuts. We could not meet our accrual goal to perform planned analysis of 40 participants.

Jonathan Zager, M.D.

Pharmacodynamics (PD) Markers

PD Markers (p70S6K, S6-RP, P-AKT, Cleaved PARP and PCNA)

Number of Participants With Pathological Response

Number of Participants With Memory CD8 T Cell Enhanced Production

Overall Study

Every eligible patient will be scanned by PET-MR at baseline and following 1 cycle of chemotherapy. PET-CT at baseline will also be obtained as it is the current standard of care and will be used to determine trial eligibility (no evidence metastasis at baseline).

Standard of care includes a baseline PET-CT and conventional CT after 2 cycles of neoadjuvant chemotherapy, and after 5-6 cycles, of neoadjuvant chemotherapy, as per current practice/ standard of care.

Patients that enroll in the trial will receive two additional PET MRI scans- one at baseline and one after 1 cycle of chemotherapy

PET MRI scan

Carol Swallow, MD, PhD

Retroperitoneal sarcoma(RPS) is a rare cancer that is difficult to cure as it typically presents as a very large abdominal mass, and complete removal with clear margins is challenging . This study will focus on improving the outcomes of surgery by treating RPS before surgery, to make resection more effective. The role of chemotherapy as a preoperative treatment for RPS is highly controversial. Response to chemotherapy is unpredictable and if the patient's tumour progresses instead of responding, the window of opportunity for resection will be lost. Conventional cross sectional imaging (CT scan) is inadequate to measure response to chemotherapy until 5-6 cycles have been given, possibly with no improvement. Thus it is critical to develop an earlier and reliable way to assess response. Functional imaging by PET scan is used in other tumour types to identify early response to treatment. PET imaging may provide a more meaningful assessment of RPS response to systemic therapy much earlier in the course of treatment than conventional imaging, allowing timely modification of the treatment plan. This study will define the role of PET imaging in evaluating early response to systemic therapy in high grade RPS, improving patient treatment.

Soft tissue sarcomas (STS) are derived from mesenchymal cells, and can arise at any site. Retroperitoneal sarcomas (RPS) account for \~15% of STS, and patients have much worse survival outcomes than for extremity STS. Local (abdominal) recurrence of RPS is very common, due to the challenges of obtaining complete resection of these large masses that abut critical central compartment structures, such as the inferior vena cava and aorta. There is currently intense interest in using preoperative therapy to downsize/cytoreduce RPS and hopefully improve oncologic outcomes. Studies have shown that preoperative radiation does not cytoreduce these tumours. In this study, the potential of systemic therapy for cytoreduction will be examined.

The standard systemic therapy regimen for treatment of patients with STS remains Adriamycin/Ifosphamide, although side effects can be tolerated only by relatively young and fit patients. The use of this regimen preoperatively for extremity STS results in average response rates of about 30-40%, as judged by histologic assessment of the resected specimen. The international experience with preoperative chemotherapy for RPS is very limited, and there are no published reports.

Functional imaging may provide a more meaningful assessment of tumour response to systemic therapy. PET-MR is a newer modality that may hold promise in assessing solid tumour response and its potential utility is currently of rapidly growing interest. Conventional MRI can offer a more detailed assessment of tumour relationships to adjacent structures than can CT, particularly in STS. Integration of PET with MR has the potential to provide information about metabolic tumour volume (MTV) and to help guide surgical planning.There are no data available on the utility of PET-MR in evaluating tumour response to chemotherapy in STS.

At present, the role of chemotherapy as a preoperative treatment for retroperitoneal sarcoma (RPS) is undefined and controversial. The sarcoma group at Princess Margaret Cancer Centre (PMCC) has had some experience with this treatment paradigm, but like most sarcoma groups in Ontario, and Canada, has reserved preoperative chemotherapy for frankly unresectable and borderline resectable tumours for which downsizing would potentially render resection more feasible. At present, CT-scan imaging is performed after 2 cycles of chemotherapy, and if there is no frank progression of the cancer, chemotherapy is continued for another 3-4 cycles. By that point the tumour is smaller on CT scan in about 30% of patients. There are 2 main problems with this approach: 1)70% of the patients may have undergone 5-6 cycles of chemotherapy with no apparent benefit; and 2) there may be a metabolic response and associated benefit without a change in tumour size. The ability to reliably assess tumour response earlier on (i.e. after 1 cycle) would significantly influence the care of these patients as ineffective chemotherapy could be terminated after 1 cycle and the regimen could be modified, or surgery could happen right away before the window of resectability is lost.

The PET- Retroperitoneal Sarcoma Study

The PET-RPS Study: Utility of PET for Assessment of Response to Preoperative Chemotherapy in Primary Retroperitoneal Sarcoma (RPS)

Pathology of RPS specimens, resected following standard ifosfamide/doxorubicin chemotherapy every 3 weeks for 5-6 cycles, will be compared with PET response (FDG uptake) after cycle 1 of chemotherapy.

Pathology of resected RPS specimens, resected following standard ifosfamide/doxorubicin chemotherapy every 3 weeks for 5-6 cycles, will be compared with CT response after 2 and 5/6 cycles of preoperative chemotherapy. PET imaging and CT imaging will be compared as prognosticators of histological response, recurrence and survival.

University Health Network, Toronto

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

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Renal Cell

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Laparoscopic or Robotic Partial Nephrectomy through transperitoneal approach

Laparoscopic or Robotic Partial Nephrectomy through retroperitoneal approach

Laparoscopic or robotic partial nephrectomy of a small renal masses (T1a) through transperitoneal or retroperitoneal approach

Laparoscopic or robotic partial nephrectomy

Seongil Seo, MD

Inhyuck Gong, Doctor

Inhyuck Gong, doctor

Both laparoscopic partial nephrectomy (LPN) and robotic partial nephrectomy (RPN) can be performed through transperitoneal (TP) or retroperitoneal (RP) approach. RP approach is less utilized than TP approach because of technical difficulties when using rigid laparoscopic instruments in the small space of retroperitoneum cavity. However, with advanced surgical skills and thoughtful patient selection, RP approach may be associated with shorter operative time (OT), less estimated blood loss (EBL), shorter length of hospital stay (LOS) compared with TP approach.

Therefore, the investigators performed randomized control trial to compare the outcomes of the two approaches (TP-LPN or RPN vs RP-LPN or RPN).

Partial nephrectomy is the standard treatment for small renal masses. The evolution of minimally invasive partial nephrectomy led to widespread utilization of laparoscopic (LPN) and robotic partial nephrectomy (RPN). Both LPN and RPN can be performed through transperitoneal (TP) or retroperitoneal (RP) approach. RP approach is less utilized than TP approach because of technical difficulties when using rigid laparoscopic instruments in the small space of retroperitoneum cavity. However, with advanced surgical skills and thoughtful patient selection, RP approach may be associated with shorter OT, less EBL, shorter LOS compared with TP approach.

Therefore, the investigators performed randomized control trial to compare the outcomes of the two approaches (TP-LPN or RPN vs RP-LPN or RPN).

The purpose of this study To compare the treatment outcomes of the transperitoneal and retroperitoneal approach during LPN or RPN in treatment of small renal masses.

Inclusion criteria During the study period, a small renal mass (less than 4cm, T1a stage) patients are going to underwent LPN or RPN.

Exclusion criteria

1. Patients who underwent radical nephrectomy
2. Patients with bilateral renal masses
3. Patients with a solitary kidney
4. Patients reject a written informed consent
5. Pregnancy

The number of target subjects More than 106 patients who meet the inclusion criteria

Transperitoneal vs Retroperitoneal Laparoscopic or Robotic Partial Nephrectomy

Comparison of Peri-operative Outcomes of Laparoscopic or Robotic Partial Nephrectomy for Small Renal Mass: Transperitoneal vs Retroperitoneal Approach

Vessel clamping time during partial nephrectomy

Disease free means no local recurrence, no metastasis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas	NCT01048723	Sarcoma	RAD001	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
The PET- Retroperitoneal Sarcoma Study	NCT04224948	Retroperitoneal...	PET MRI scan	18 Years -	University Health Network, Toronto
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
Transperitoneal vs Retroperitoneal Laparoscopic or Robotic Partial Nephrectomy	NCT02849119	Renal Cell Carc...	Laparoscopic or...	-	Samsung Medical Center

Spots Global Cancer Trial Database for retroperitoneal