Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Angiogenesis Inhibitors

Ifosfamide

Isophosphamide mustard

Mechlorethamine

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive pazopanib hydrochloride PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Patients receive placebo PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride

External Beam Radiation Therapy

Laboratory Biomarker Analysis

Pazopanib Hydrochloride

Pharmacological Study

Placebo

Therapeutic Conventional Surgery

Darin Davidson

This randomized pilot clinical trial studies pazopanib hydrochloride followed by chemotherapy and surgery in treating patients with soft tissue sarcoma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes that are needed for cell growth and may also stop the growth of soft tissue sarcoma by blocking blood flow to the tumor. Giving pazopanib hydrochloride and chemotherapy before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed.

PRIMARY OBJECTIVES:

I. To determine the absolute values and changes in standardized uptake values (SUV) by fludeoxyglucose F18 (FDG)-positron emission tomography (PET) before and after a 14 day Run-in period of pazopanib (pazopanib hydrochloride) versus placebo, and to compare this to the change in SUV following pre-operative chemotherapy.

II. To evaluate the correlation between antiangiogenic activity and pazopanib drug exposure.

III. To assess the response rate by Response Evaluation Criteria In Solid Tumors (RECIST) criteria after the 14 day Run-in period of pazopanib versus placebo and compare this to the response rate following pre-operative chemotherapy.

SECONDARY OBJECTIVES:

I. To examine the activity of antiangiogenic therapy with pazopanib combined with pre-operative chemotherapy for high risk extremity soft tissue sarcomas as measured by: histological necrosis at surgery; change in plasma and tumor biomarker assays of angiogenesis

II. To evaluate the safety of sequential treatment with pazopanib and pre-operative chemotherapy with doxorubicin (doxorubicin hydrochloride) and ifosfamide.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

All patients then receive neoadjuvant chemotherapy comprising doxorubicin hydrochloride intravenously (IV) continuously over days 1-3 and ifosfamide IV on days 1-5. Treatment repeats every 21 days for 4 courses. Beginning 2-4 weeks later, all patients undergo surgery followed by 2 more courses of chemotherapy 2-4 weeks after completion of surgery. Some patients may also undergo adjuvant external beam radiation therapy 5 days a week for 5 days followed by a boost. Patients treated on Arm I may resume pazopanib hydrochloride 1 week after completion of all adjuvant therapy for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Pazopanib Hydrochloride Followed by Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma

The Effect of Antiangiogenic Therapy With Pazopanib Prior to Preoperative Chemotherapy for Subjects With Extremity Soft Tissue Sarcomas: A Randomized Study to Evaluate Response by Imaging

Change in maximum SUV (standardized uptake value) of tumors measured by FDG-PET. Comparison conducted using a two-sided Wilcoxon rank sum test.

Change in maximum SUV of tumors measured by FDG-PET. Comparison conducted using a two-sided Wilcoxon rank sum test.

RECIST measurements will be performed on serial MRIs to evaluate the correlation with FDG-PET. The longest diameter (LD) of the target lesions will be measured and reported as the baseline LD. The baseline LD will be used as reference to further characterize the objective tumor response of the measurable dimension of the disease.Per 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 (PD), 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

Trough plasma pazopanib concentration measured during the 14 day run-in period on days 10 through 14.

Plasma will be collected for measurement of VEGF and soluble VEGFR2 (sVEGFR2) at baseline, after the 14 day Run-in period of pazopanib, after completion of neoadjuvant chemotherapy and approximately every 3 months thereafter until completion of pazopanib maintenance therapy, when indicated. Quantitative enzyme-linked immunosorbent assays (ELISA) for VEGF and sVEGFR2 will be performed on plasma and tumor extracts. Plasma will also be collected for micro RNA at baseline, after the 14 day Run-in period of pazopanib, following neoadjuvant chemotherapy and every 3 months thereafter until completion of pazopanib maintenance therapy, when indicated.

Defined as the interval of time from randomization until death from any cause.

Estimate the amount of viable tumor, and report the percentage of necrosis. Analysis was only completed on a subset of participants.

Defined as the duration of time from randomization to progressive disease (per RECIST), local recurrence, distant metastatic disease (exclusive of stage IV subjects), or death, whichever occurs first.

National Cancer Institute (NCI)

University of Washington

Patients receive pazopanib hydrochloride PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride: Given IV External Beam Radiation Therapy: Undergo external beam radiation therapy Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pazopanib Hydrochloride: Given PO Pharmacological Study: Correlative studies Therapeutic Conventional Surgery: Undergo surgery

Pazopanib

Patients receive placebo PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride: Given IV External Beam Radiation Therapy: Undergo external beam radiation therapy Ifosfamide: Given IV Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies Placebo: Given PO Therapeutic Conventional Surgery: Undergo surgery

Patients receive pazopanib hydrochloride or placebo PO QD. Patient did not complete study and thus treatment arm remains blinded.

Blinded

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Screening SUV

Dr Darin Davidson

Change in Maximum SUV of Tumors Measured by FDG-PET Pre- and Post Receipt of Pazopanib Versus Placebo

8 week PET not done on one Pazopanib participant.

Change in Maximum SUV of Tumors Measured by FDG-PET Post Receipt of 2 Courses of Preoperative Chemotherapy

Per 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 LD of target lesions; Progression (PD),20% increase in the sum of the LD of target lesions,or measurable increase in a non-target lesion,or appearance of new lesions.",

Tumor Response by RECIST Criteria

8 week MRI not done on one Placebo patient.

Pharmacokinetic Profile of Pazopanib

Change in Levels of VEGF and Soluble VEGFR2 Assessed by ELISA on Plasma and Tumor Extracts

Overall Survival

Number of Participants With Pathologic Response at the Time of Surgery as Measured by % Tumor Viability ( >= 95% Necrosis)

Patients receive pazopanib hydrochloride PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride: Given IV

External Beam Radiation Therapy: Undergo external beam radiation therapy

Ifosfamide: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pazopanib Hydrochloride: Given PO

Pharmacological Study: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Arm I (Pazopanib Hydrochloride)

Patients receive placebo PO QD. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride: Given IV

External Beam Radiation Therapy: Undergo external beam radiation therapy

Ifosfamide: Given IV

Laboratory Biomarker Analysis: Correlative studies

Pharmacological Study: Correlative studies

Placebo: Given PO

Therapeutic Conventional Surgery: Undergo surgery

Arm II (Placebo)

Progression Free Survival

Overall Study

Alovudine

Antiviral Agents

Patients receive fluorothymidine F-18 IV over 1 minute and undergo PET scan over 60 minutes 21 or less days prior to standard of care radiation therapy and 14 or less days prior to the standard of care surgery.

Fluorothymidine F-18

Positron Emission Tomography

Arthur Y Hung, MD

This pilot early phase I trial studies how well fluorothymidine F-18 positron emission tomography (PET) works in imaging patients with intermediate or high grade soft tissue sarcoma. Fluorothymidine F-18 PET may provide useful information about the tumor's response to treatment and may give the doctors early results that would better help to plan the post-surgical therapy.

PRIMARY OBJECTIVES:

I. To determine fluorothymidine F-18 (¹⁸F-FLT) uptake parameters before and after radiotherapy.

SECONDARY OBJECTIVES:

I. To correlate ¹⁸F-FLT uptake post-radiotherapy scan with pathologic response. II. To correlate levels the mitotic index in surgical specimens with the ¹⁸F-FLT uptake in post-radiation scans.

III. To correlate ¹⁸F-FLT uptake both pre- and post-radiotherapy with magnetic resonance imaging (MRI) enhancement both within and around the tumor.

TERTIARY OBJECTIVES:

I. To compare ¹⁸F-FLT uptake and fludeoxyglucose F-18 (FDG) uptake when FDG-PET-computed tomography (CT) is available, pre-radiation, post-radiation, or both.

II. To compare ¹⁸F-FLT uptake in post-radiation scans with local recurrences looking for spatial correlation.

OUTLINE:

Patients receive fluorothymidine F-18 intravenously (IV) over 1 minute and undergo PET scan over 60 minutes 21 or less days prior to standard of care radiation therapy and 14 or less days prior to the standard of care surgery.

After completion of study, patients are followed up for 2 years.

Fluorothymidine F-18 PET in Diagnosing Patients With Intermediate or High Grade Soft Tissue Sarcoma

A Pilot Study Investigating ¹⁸F-FLT-PET as a Marker of Response to Preoperative Radiotherapy in Soft Tissue Sarcoma

Measured by mean SUV where the response to therapy is Pathological Response Disease change in volume of tumor (in cm3) utilizing Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) with magnetic resonance imaging (MRI). Mean, median, standard deviation, and range will be reported for continuous variables. Box plot, histogram plot, and density plot may be used to graphically show the distribution of the continuous endpoints.

Measured by peak SUV value where the response to therapy is Pathological Response Disease change in volume of tumor (in cm3) utilizing Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) with magnetic resonance imaging (MRI). Mean, median, standard deviation, and range will be reported for continuous variables. Box plot, histogram plot, and density plot may be used to graphically show the distribution of the continuous endpoints.

Measured as Ki-67. Will assess the mitotic index of resection tissue. Spearman's correlation coefficient will be computed to assess the association between the mitotic index and fluorothymidine F-18 uptake parameters in post-radiation scans.

Measured as Ki-67. Evaluated by the standard of care magnetic resonance imaging. Will assess the size and location of irregularly increased T2-weighted signal intensity. Descriptive statistical analysis will be conducted

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pazopanib Hydrochloride Followed by Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma	NCT01446809	Stage IIA Adult... Stage III Adult... Stage IV Adult ...	Doxorubicin Hyd... External Beam R... Ifosfamide Laboratory Biom... Pazopanib Hydro... Pharmacological... Placebo Therapeutic Con...	18 Years -	University of Washington
Fluorothymidine F-18 PET in Diagnosing Patients With Intermediate or High Grade Soft Tissue Sarcoma	NCT03613259	Stage II Adult ... Stage IIA Adult... Stage IIB Adult... Stage IIC Adult... Stage III Adult... Stage IV Adult ...	Fluorothymidine... Laboratory Biom... Positron Emissi...	18 Years -	OHSU Knight Cancer Institute

Spots Global Cancer Trial Database for stage iia adult soft tissue sarcoma