AZD0530 in Treating Patients With Recurrent Locally Advanced or Metastatic Soft Tissue Sarcoma

A Phase 2 Study of AZD0530 in Recurrent or Metastatic Soft Tissue Sarcoma

This phase II trial is studying how well AZD0530 works in treating patients with recurrent locally advanced, or metastatic soft tissue sarcoma. AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

• Status: Completed
• Conditions: Uterine Carcinosarcoma; Endometrial Stromal Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Uterine Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Dermatofibrosarcoma Protuberans; Adult Rhabdomyosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Uterine Leiomyosarcoma
• Intervention / Treatment: Drug: saracatinib

Detailed Description

OBJECTIVES:

I. To assess the efficacy of AZD0530, in terms of disease control rate (i.e., response rate and stable disease rate), in patients with recurrent locally advanced or metastatic soft tissue sarcoma.

II. To assess the toxicity, time to progression, and response duration of AZD0530 in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 8 weeks.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Montreal General Hospital
• United States
  • Pennsylvania
    • Rockledge, Pennsylvania, United States, 19046
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Leukocytes >= 3,000/mcL

• Histologically or cytologically confirmed soft tissue sarcoma including, but not limited to any of:

  • Malignant fibrous histiocytoma
  • Fibrosarcoma - non infantile
  • Leiomyosarcoma - not uterine
  • Liposarcoma
  • Non-rhabdomyosarcoma soft tissue sarcoma
  • Rhabdomyosarcoma, not otherwise specified
  • Carcinosarcoma of the uterus
  • Dermatofibrosarcoma
  • Endometrial stromal sarcoma
  • Leiomyosarcoma - uterus

• Recurrent or locally advanced or metastatic disease

  • No more than two prior lines of chemotherapy for metastatic disease (not including adjuvant chemotherapy)

• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan

  • Target measurable lesion must not have been in previous radiation portal, unless progression of this lesion after radiotherapy has been documented
• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• Recovered from all prior therapy
• Platelet count >= 100,000/mcL
• Hemoglobin > 9 g/dL
• Total bilirubin =< 1.25 times upper limit of normal (ULN)
• AST and ALT =< 3 times ULN
• Creatinine =< 1.5 times ULN OR creatinine clearance >= 50 mL/min
• Urine protein:creatinine ratio =< 1.0 OR 24-hour urine protein < 1,000 mg
• ANC >1,500/mcL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 8 weeks after completion of study therapy
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
• No QTc prolongation (defined as a QTc interval >= to 460 msecs) or other significant ECG abnormalities
• No poorly controlled hypertension (i.e., systolic blood pressure (BP) >= 140 mm Hg, or diastolic BP >= 90 mm Hg)

• No condition that impairs a patient's ability to swallow AZD0530 tablets, including any of the following:

  • Gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
  • Prior surgical procedures affecting absorption
  • Active peptic ulcer disease

Exclusion Criteria:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• No intercurrent cardiac dysfunction including, but not limited to, any of the following:

  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
• No history of ischemic heart disease, including myocardial infarction
• No uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• More than 4 weeks since prior radiotherapy
• More than 7 days since prior and no concurrent prohibited CYP3A4-active agents or substances
• No other concurrent investigational agents or commercial agents or therapies
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No known brain metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral AZD0530 (saracatinib ) at a dose of 175 mg, once daily, in the absence of disease progression or unacceptable toxicity.	Drug: saracatinib; Given orally; Other Names: AZD0530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate, Defined as the Number of Patients Who Achieved Complete Response, Partial Response or Stable Disease For a Period of More Than 4 Months.	Response and progression will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Changes in only the largest diameter (unidimensional measurement) of the tumor lesions; where CR is disappearance of all target lesions, PR is at least 30% decrease in the sum of longest diameter, PD is at least 20% increase in the sum of longest diameter recorded since the treatment started and SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions	Up to 5 years
Overall Survival	Median was estimated. The Kaplan-Meier method will be used to estimate overall survival estimates.	Up to 5 years
Stable Disease Rate	Achieved stable disease as their best response	Up to 5 years
Duration of Response	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Tumor Response "of more than 4 months" was counted toward the Disease Control Rate.	Up to 5 years
Time to Disease Progression	The Kaplan-Meier method will be used to estimate time to progression estimates. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Margaret von Mehren, University Health Network-Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: April 15, 2008
• First Submitted That Met QC Criteria: April 15, 2008
• First Posted (Estimate): April 16, 2008

Study Record Updates

• Last Update Posted (Actual): June 29, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Disease Attributes; Neoplasms, Complex and Mixed; Neoplasms, Connective Tissue; Endometrial Neoplasms; Neoplasms, Muscle Tissue; Neoplasms, Adipose Tissue; Myosarcoma; Neoplasms, Fibrous Tissue; Endometrial Stromal Tumors; Sarcoma; Recurrence; Carcinosarcoma; Leiomyosarcoma; Liposarcoma; Rhabdomyosarcoma; Dermatofibrosarcoma; Histiocytoma, Malignant Fibrous; Fibrosarcoma; Histiocytoma; Histiocytoma, Benign Fibrous; Sarcoma, Endometrial Stromal; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Saracatinib
• Other Study ID Numbers: NCI-2009-01054; N01CM62203 (U.S. NIH Grant/Contract); PHL-054 (Other Grant/Funding Number: N01CM62203); CDR0000588034 (Other Grant/Funding Number: N01CM62203); PMH-PHL-054 (Other Grant/Funding Number: N01CM62203)