Neoplasms

All Conditions

Nervous System Diseases

Rare Diseases

Sarcoma

Histiocytoma, Malignant Fibrous

Liposarcoma

Fibrosarcoma

Histiocytoma

Histiocytoma, Benign Fibrous

Leiomyosarcoma

Sarcoma, Synovial

Nerve Sheath Neoplasms

Neurofibrosarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Malignant Peripheral Nerve Sheath Tumor

Epithelioid Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Fluorodeoxyglucose F18

Ifosfamide

Isophosphamide mustard

Mesna

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Radiopharmaceuticals

Subjects with soft tissue sarcoma who are receiving pegylated liposomal doxorubicin hydrochloride, Ifosfamide with mesna and pegfilgrastim - Repeat every 28 days for 4 cycles total

Subjects with soft tissue sarcoma who are receiving Doxorubicin hydrochloride, Ifosfamide with mesna and pegfilgrastim - Repeat every 28 days for 4 cycles total

will be given at 6 mg subcutaneously (SC) at the end of the mesna infusion

pegfilgrastim

65 mg/m\^2 by continuous intravenous (IV) infusion over 7 days beginning on day 1

doxorubicin hydrochloride

9 g/m\^2 by continuous intravenous (IV) infusion over 6 days beginning on day 1 with mesna 10.5 g/m\^2 by continuous IV infusion over 7 days beginning on day 1

ifosfamide

45 mg/m2 intravenous (IV) Day 1, repeat every 28 days.

pegylated liposomal doxorubicin hydrochloride

The surgical procedure will be decided by the treating physician and independent of study participation

conventional surgery

FDG is a radioactive sugar equal to a uniform whole-body exposure of approximately 1.5 rem for each scan. Post-operative radiation therapy may be given according to institutional guidelines in patients felt to have close surgical margins.

fludeoxyglucose F 18

Edward Cheng, MD

RATIONALE: Diagnostic procedures, such as positron emission tomography (PET) scan and computated tomography (CT) scan, may help doctors predict a patient's response to treatment and may help plan the best treatment. Drugs used in chemotherapy, such as doxorubicin and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This clinical trial is studying how well PET scan combined with CT scan predicts response in patients undergoing chemotherapy and surgery for soft tissue sarcoma.

OBJECTIVES:

Primary

* Determine whether measurements of fludeoxyglucose (FDG) positron emission tomography (PET)/CT imaging can accurately predict disease-free survival of patients with soft tissue sarcoma who are receiving neoadjuvant chemotherapy.

Secondary

* Correlate histological response to neoadjuvant chemotherapy for soft tissue sarcomas with FDG-PET/CT imaging findings.

Tertiary

* Determine the changes in FDG-PET/CT imaging over time as each course of chemotherapy is given.

OUTLINE: Patients receive 1 of 2 standard chemotherapy regimens:

* Preferred regimen: Patients receive pegylated doxorubicin HCl liposome IV on day 1, ifosfamide IV continuously on days 1-6, and pegfilgrastim subcutaneously (SC) on day 8. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
* Alternative regimen: Patients receive doxorubicin hydrochloride IV continuously on days 1-7. Patients also receive ifosfamide and pegfilgrastim as in the preferred regimen. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

All patients undergo a fludeoxyglucose positron emission tomography/CT scan at baseline, after course 1, and after completion of chemotherapy. Patients undergo surgery within 4-6 weeks after completion of chemotherapy.

After completion of study treatment and surgery, patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.

PET CT as Predictor of Response in Preoperative Chemotherapy for Soft Tissue Sarcoma

An Evaluation of PET/CT Imaging as a Predictor of Disease Free Survival Following Neo-Adjuvant Chemotherapy for Soft Tissue Sarcoma

Compare changes in baseline and follow-up fludeoxyglucose (FDG) positron emission tomography (PET)/CT imaging with disease-free survival by peak SUV and max SUV calculations. Changes in baseline and follow-up PET/CT, based on max SUV calculations, will be compared with disease free survival. Disease free survival will be measured in months from the time of study enrollment until the time that disease recurrence/relapse/progression is recorded.

The overall histologic response will be defined as:

% histologic response = 100 - % viable tumor in the central slice as assessed histologically It should be noted that the % histologic response is different from % tumor necrosis as it includes an assessment of the % tumor necrosis along with the degenerative changes

Changes in PET/CT from baseline will be compared to PET/CT done after one cycle and after completion of chemotherapy treatment before surgical excision using max SUV calculations.

Masonic Cancer Center, University of Minnesota

Symptoms and General Pathology

Recurrence

Osteosarcoma

Sarcoma, Ewing

Chondrosarcoma

Rhabdomyosarcoma

Ewing Sarcoma

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Clotrimazole

Miconazole

Antifungal Agents

Single arm study: Dose escalation of temsirolimus plus constant dose of liposomal doxorubicin.

Patients were treated with temsirolimus (Torisel) weekly by IV and with liposomal doxorubicin (Doxil) (standard dose) by IV once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until dose limiting toxicity (DLT) occurred and the maximally tolerated dose (MTD) was identified. The MTD dose was the standard dose of temsirolimus used for the remainder of the study. Dose modifications were based on protocol parameters for toxicities.

temsirolimus plus liposomal doxorubicin

David M Loeb, MD, PhD

The purpose of this study is to identify a safe dosing regimen for the combination of Torisel and liposomal doxorubicin in patients with recurrent sarcoma. A secondary purpose of the study is to determine how effective this combination is for the treatment of recurrent sarcoma.

The effectiveness of treatments for recurrent sarcomas is quite limited. One hypothesis to explain the refractory nature of recurrent sarcomas is the existence of chemotherapy-resistant sarcoma stem cells.

Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma

Phase I/II Trial of Torisel and Liposomal Doxorubicin in Patients With Advanced Soft Tissue and Bone Sarcomas

Dose limiting toxicities in each dose cohort.

Number of days from day 1 of treatment until date of death from any cause.

Interval from Date of start of treatment to date of disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression.

Number of participants who completed at least 2 treatment cycles with evidence of response. Response is defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS

AUC was calculated using a single compartment model.

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS.

Interval from start of treatment to disease progression or death from any cause. Disease progression is defined as at least 20% increase in sum of longest diameter of target lesions or appearance of any new lesions. Subjective determination of significant worsening of disease-related symptoms was considered clinical disease progression

Number of days after 2 cycles of treatment, until maximal response is observed.

Number of days until documentation of disease progression or date of death from other cause

Number of days from documented improvement to disease progression.

National Comprehensive Cancer Network

Wyeth is now a wholly owned subsidiary of Pfizer

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Single arm consists of temsirolimus (Torisel) plus liposomal doxorubicin (Doxil). Temsirolimus is administered IV in sequentially escalating cohorts at doses between 15 and 50 mg/M2 (body surface area), once weekly. Liposomal doxorubicin is administered IV at 30 mg per M2 (body surface area) once every 28 days. Treatment may continue with both drugs for 2 years. Temsirolimus may continue beyond 2 years.

temsirolimus plus liposomal doxorubicin: Patients will be treated with temsirolimus (Torisel) temsirolimus weekly by iv and with liposomal doxorubicin (Doxil) (standard dose) by iv once every 28 days. Cohorts of patients receive sequentially increasing dose of temsirolimus until maximally tolerated dose (MTD) is reached. Once MTD (standard dose) is achieved, dosing will be with standard doses for each drug, but dosing will be modified based on toxicity.

Temsirolimus Plus Liposomal Doxorubicin

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

David M. Loeb, M.D., Ph.D.

Temsirolimus 15 mg/m^2

Temsirolimus 20 mg/m^2

Temsirolimus 27 mg/m^2

Number of Subjects Who Experienced Dose-Limiting Toxicities

Part 1: Incidence of Dose Limiting Toxicities

Subjects who received Temsirolimus MTD, 20 mg/m\^2 in Phase I of the study and all subjects in the Phase II study were included. from both Phase I and Phase II of the study are included.

Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

The number of analyzed participants does not include the 2 participants treated at the MTD who stopped treatment for early disease-related adverse events.

Part 2: Median Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Subjects who received Temsirolimus MTD, 20 mg/m\^2 in Phase I of the study and all subjects in the Phase II study were included from both Phase I and Phase II of the study who were not taken off study for early toxicity were included. Two of the eighteen subjects who were treated at the MTD were excluded.

Median Progression-free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Subjects who completed at least 2 cycles of treatment with temsirolimus dose of 20 mg/m\^2 or 27 mg/m\^2 were assessed for radiologic response.

Temsirolimus 20 mg/m^2 and 27 mg/m^2

Only participants who completed at least 2 treatment cycles (14/18 participants) were included to assess this outcome measure.

Objective Response Rate

Temsirolimus- Parent Drug

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. Cmax of Sirolimus was calculated using a non-compartmental model.

Sirolimus- Active Metabolite

Seven subjects had complete series of blood samples available for evaluation for both Temsirolimus, the parent drug and Sirolimus, the active metabolite. The number (N) evaluable participants is less than the number of participants from whom samples were collected due to inadvertent processing mishaps.

Maximum Observed Plasma Concentration (Cmax)

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. AUC was calculated using a single compartment model.

Whole blood temsirolimus and sirolimus levels were measured by LC/MS/MS. AUC was calculated using a single non- compartment model.

Seven subjects had complete series of blood samples available for evaluation for both Temsirolimus, the parent drug and Sirolimus, the active metabolite. The analysis was per protocol. The number (N) evaluable samples is less than the number of collected samples due to inadvertent processing mishaps.

Area Under the Curve (AUC)

Clearance was calculated using a single compartment model.

Drug Clearance

All subjects who received at least one dose of temsirolimus at the MTD, 20 mg/M\^2 plus liposomal doxorubicin were included.

Subjects Who Received Temsirolimus MTD, 20 mg/m^2

Mean Progression Free Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Subjects who received Temsirolimus MTD, 20 mg/m\^2 in Phase I of the study and all subjects in the Phase II study were included from both Phase I and Phase II of the study are included.

Mean Overall Survival of Subjects Who Were Treated at the Temsirolimus MTD, 20 mg/m^2

Although the original protocol specified that "time to maximal response" would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.

Time to Response

Although the original protocol specified that "duration of response" would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.

Duration of Response

Although the original protocol specified that "clinical benefit rate" would be an outcome measure that would be obtained, appropriate data were not collected, so this outcome measure cannot be evaluated or reported.

Clinical Benefit Rate

Cohort 1, Dose Level 3

Cohort 2, Dose Level 4

Cohort 3, Dose Level 5

Overall Study

Digestive System Diseases

Skin and Connective Tissue Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Adipose Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Amino Acids

Sunitinib

Tyrosine Kinase Inhibitors

Imatinib Mesylate

Angiogenesis Inhibitors

Growth Inhibitors

Tyrosine

Sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks

For each 6 week cycle, patients will take SU011248 every day in the morning for 4 weeks followed by a 2 week rest period.

Sunitinib Malate (SU011248)

Alberto Chiappori, M.D.

This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity.

All patients with unresectable or metastatic soft tissue sarcoma (STS): leiomyosarcoma, liposarcoma, fibrosarcoma, and malignant fibrous histiocytoma (MFH) seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study.

This is an open label single site Phase II clinical trial to identify a potentially promising therapy dose for Sunitinib malate, an oral multi-kinase inhibitor. The study drug will be taken orally once daily on days 1 through 28 of each 42 day cycle. Treatment will be continued until there is either disease progression or cumulative/acute toxicity which in the opinion of the treating physician or the trial Principal Investigator (PI) compromises the ability of the patient to receive treatment or the patient desires to stop treatment.

All patients with unresectable or metastatic STS: leiomyosarcoma, liposarcoma, fibrosarcoma, and MFH seen at the Moffitt Cancer Center will be screened for eligibility to be enrolled in the study.

An office visit will be required before the beginning of every cycle every 6 weeks to assess toxicity and for physical examination. Complete blood count (CBC) and differential, comprehensive metabolic panel, and electrocardiogram (ECG) will be obtained at every scheduled visit.

Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma

Phase II Open-Label Study of Sunitinib Malate (SU011248) in Adult Patients With Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma

Objective Radiographic Response Rate. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST).

Time to tumor progression defined as the duration of time from start of treatment to time of progression. Response assessments were based on the longest diameter tumor measurements in accordance with Response Evaluation Criteria in Solid Tumors (RECIST).

The median OS times (months) for liposarcoma, leiomyosarcoma and MFH.

Determine the number of participants who experience Serious Adverse events while on sunitinib malate study.

Pfizer

H. Lee Moffitt Cancer Center and Research Institute

Experimental: Sunitinib Malate (SU011248) Treatment

The trial was amended to exclude fibrosarcoma after only one patient was accrued while the other cohorts had completed 75% or more of their planned accrual. Only patients with liposarcoma, leiomyosarcoma, or MFH were enrolled after this amendment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PET CT as Predictor of Response in Preoperative Chemotherapy for Soft Tissue Sarcoma	NCT00346125	Sarcoma	pegfilgrastim doxorubicin hyd... ifosfamide pegylated lipos... conventional su... fludeoxyglucose...	16 Years -	Masonic Cancer Center, University of Minnesota
Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma	NCT00949325	Sarcoma	temsirolimus pl...	1 Year -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PET CT as Predictor of Response in Preoperative Chemotherapy for Soft Tissue Sarcoma	NCT00346125	Sarcoma	pegfilgrastim doxorubicin hyd... ifosfamide pegylated lipos... conventional su... fludeoxyglucose...	16 Years -	Masonic Cancer Center, University of Minnesota
Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma	NCT00949325	Sarcoma	temsirolimus pl...	1 Year -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma	NCT00400569	Liposarcoma Leiomyosarcoma Fibrosarcoma Malignant Fibro...	Sunitinib Malat...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for malignant fibrous histiocytoma