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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00659360
• Collaborator: (none)
• Enrollment: 17
• Locations: 4
• Arm: 1
• Duration (Months): 57
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Rhabdomyosarcoma; Dermatofibrosarcoma Protuberans; 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; Uterine Carcinosarcoma; Uterine Leiomyosarcoma	Drug: saracatinib	Phase 2

Detailed Description

OBJECTIVES:

1. 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.

2. 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 Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of AZD0530 in Recurrent or Metastatic Soft Tissue Sarcoma
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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. [Up to 5 years]

   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

Secondary Outcome Measures

1. Objective Response Rate [Up to 5 years]

   Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions

2. Overall Survival [Up to 5 years]

   Median was estimated. The Kaplan-Meier method will be used to estimate overall survival estimates.

3. Stable Disease Rate [Up to 5 years]

   Achieved stable disease as their best response

4. Duration of Response [Up to 5 years]

   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.

5. Time to Disease Progression [Up to 5 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fox Chase Cancer Center	Rockledge	Pennsylvania	United States	19046
2	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
3	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
4	Montreal General Hospital	Montreal	Quebec	Canada	H3G 1A4

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Margaret von Mehren, University Health Network-Princess Margaret Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00659360
• Other Study ID Numbers: NCI-2009-01054; PHL-054; CDR0000588034; PMH-PHL-054; N01CM62203
• First Posted: Apr 16, 2008
• Last Update Posted: Jun 29, 2018
• Last Verified: May 1, 2018

• Additional relevant MeSH terms: Sarcoma; Rhabdomyosarcoma; Leiomyosarcoma; Liposarcoma; Carcinosarcoma; Fibrosarcoma; Histiocytoma; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous; Dermatofibrosarcoma; Sarcoma, Endometrial Stromal; Recurrence; Saracatinib

Study Results

Participant Flow

Arm/Group Title	Arm I AZD0530
Arm/Group Description	Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Period Title: Overall Study
STARTED	17
COMPLETED	17
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Overall Participants	17
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 47.1%
>=65 years	9 52.9%
Sex: Female, Male (Count of Participants)
Female	11 64.7%
Male	6 35.3%
Region of Enrollment (participants) [Number]
United States	8 47.1%
Canada	9 52.9%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Measure Participants	17
Number [participants]	0 0%

2. Secondary Outcome

Title	Objective Response Rate
Description	Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 (saracatinib ) at a dose of 175 mg, once daily, in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Measure Participants	17
Number [participants]	0 0%

3. Secondary Outcome

Title	Overall Survival
Description	Median was estimated. The Kaplan-Meier method will be used to estimate overall survival estimates.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 (saracatinib ) at a dose of 175 mg, once daily, in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Measure Participants	17
Median (95% Confidence Interval) [months]	16.1

4. Secondary Outcome

Title	Stable Disease Rate
Description	Achieved stable disease as their best response
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 (saracatinib ) at a dose of 175 mg, once daily, in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Measure Participants	17
Number [participants]	2 11.8%

5. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Patients who had partial response, complete response or stable disease

Arm/Group Title	Arm I AZD0530
Arm/Group Description	Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Measure Participants	17
Number [participants]	0 0%

6. Secondary Outcome

Title	Time to Disease Progression
Description	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.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 (saracatinib ) at a dose of 175 mg, once daily, in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
Measure Participants	17
Median (95% Confidence Interval) [months]	1.7

Adverse Events

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral AZD0530 once daily in the absence of disease progression or unacceptable toxicity. saracatinib: Given orally
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	5/17 (29.4%)
Blood and lymphatic system disorders
Anemia	2/17 (11.8%)
General disorders
Fever	2/17 (11.8%)
Fatigue	1/17 (5.9%)
Investigations
Lymphocyte count decreased	2/17 (11.8%)
Aspartate aminotransferase increased	1/17 (5.9%)
Blood bilirubin increased	1/17 (5.9%)
Metabolism and nutrition disorders
Hypokalemia	1/17 (5.9%)
Renal and urinary disorders
Proteinuria	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders - Other, specify - unspecified	2/17 (11.8%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	17/17 (100%)
Blood and lymphatic system disorders
Anemia	12/17 (70.6%)
General disorders
Fatigue	13/17 (76.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.