Saracatinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
Study Details
Study Description
Brief Summary
This phase II trial is studying the how well saracatinib works in treating patients with metastatic or recurrent head and neck cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth
Detailed Description
PRIMARY OBJECTIVES:
- To determine the median progression-free survival for patients with advanced or recurrent squamous cell carcinoma of the head and neck (HNSCC) treated with AZD0530 (saracatinib).
SECONDARY OBJEC TIVES:
-
To determine overall survival for patients with advanced or recurrent HNSCC treated with AZD0530.
-
To determine objective response rate for patients with advanced or recurrent HNSCC treated with AZD0530.
-
For patients with accessible tumors, to perform pre and post-treatment biopsies to assess the pharmacodynamic effects of AZD0530 on c-Src and downstream signaling molecules STAT3 and STAT5.
OUTLINE:
Patients receive saracatinib orally (PO) or by percutaneous endoscopic gastrostomy (PEG) tube once daily (QD) on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 12 weeks and then periodically thereafter.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (enzyme inhibitor therapy) Patients receive saracatinib PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. |
Drug: saracatinib
Given PO
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate [From the start of treatment for up to 12 weeks]
Response was determined as inicated in the protocol.
Secondary Outcome Measures
- Overall Survival [Up to 12 weeks]
The Kaplan-Meier method will be used to estimate overall survival.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
-
Persistent, recurrent, or metastatic disease that is not amenable to curative-intent therapy with surgery or radiation
-
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral computed tomography (CT) scan
-
Karnofsky performance status ≥ 60%
-
White blood cell (WBC) ≥ 3,000/mcL
-
Absolute neutrophil count ≥ 1,500/mcL
-
Platelets ≥ 100,000/mcL
-
Hemoglobin > 9 g/dL
-
Total bilirubin within upper institutional limits of normal (ULN)
-
Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ≤ 2.5 x ULN
-
Creatinine within ULN OR creatinine clearance ≥ 60 mL/min
-
Patients must agree to use adequate birth control for the duration of study participation and for at least 8 weeks after discontinuation of study drug
-
May have received 1 prior cytotoxic chemotherapy regimen for recurrent or metastatic disease
Exclusion Criteria:
-
Known brain metastases
-
History of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
-
Urine protein: creatinine ratio ≥ 1.0 OR 24-hour urine protein ≥ 1,000 mg
-
QTc prolongation ≥ 480 msecs
-
Intercurrent symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
-
History of myocardial infarction within the past year
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
-
Pregnant or breastfeeding women
-
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
-
Pulmonary fibrosis ≥ grade 2, pleural effusion (non-malignant) ≥ grade 2, or pneumonitis/pulmonary infiltrates ≥ grade 2
-
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
-
Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
-
Use of specifically prohibited cytochrome P450 3A4 (CYP3A4)-active agents or substances
-
Prohibited drugs should be discontinued 7 days prior to the administration of the first dose of AZD0530 and for 7 days following discontinuation of AZD0530
-
Patients receiving any other investigational agents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Matthew Fury, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2009-00192
- 06-074
- CDR0000559632
- N01CM62206
- NCT01645618
- NCT01664468
Study Results
Participant Flow
| Recruitment Details | Protocol Open to Accrual 08/22/2006 Protocol Closed to Accrual 07/14/2009 Primary Completion Date 03/08/2011 Recruitment Location is the medical clinic |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment (Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive saracatinib 175 mg PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. |
| Period Title: Overall Study | |
| STARTED | 9 |
| COMPLETED | 9 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment (Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive saracatinib PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. |
| Overall Participants | 9 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
7
77.8%
|
| >=65 years |
2
22.2%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
53.8
(13.7)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
22.2%
|
| Male |
7
77.8%
|
| Region of Enrollment (participants) [Number] | |
| United States |
9
100%
|
Outcome Measures
| Title | Overall Response Rate |
|---|---|
| Description | Response was determined as inicated in the protocol. |
| Time Frame | From the start of treatment for up to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive saracatinib PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 9 |
| Stable Disease |
1
11.1%
|
| Progression of Disease |
8
88.9%
|
| Title | Overall Survival |
|---|---|
| Description | The Kaplan-Meier method will be used to estimate overall survival. |
| Time Frame | Up to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment (Enzyme Inhibitor Therapy) |
|---|---|
| Arm/Group Description | Patients receive saracatinib PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. |
| Measure Participants | 9 |
| Median (Full Range) [Days] |
180
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Treatment (Enzyme Inhibitor Therapy) | |
| Arm/Group Description | Patients receive saracatinib PO or by PEG tube QD on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. | |
All Cause Mortality |
||
| Treatment (Enzyme Inhibitor Therapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Treatment (Enzyme Inhibitor Therapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/9 (55.6%) | |
| Blood and lymphatic system disorders | ||
| Lymphopenia | 2/9 (22.2%) | 2 |
| Inf norm ANC/gr1/2 neut-Cellulitis(skin) | 1/9 (11.1%) | 1 |
| General disorders | ||
| Death not assoc w CTCAE term- Sudden death | 3/9 (33.3%) | 3 |
Other (Not Including Serious) Adverse Events |
||
| Treatment (Enzyme Inhibitor Therapy) | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/9 (100%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin decreased | 4/9 (44.4%) | 4 |
| Lymphopenia | 2/9 (22.2%) | 2 |
| Platelets | 2/9 (22.2%) | 2 |
| Epistaxis | 2/9 (22.2%) | 2 |
| Gastrointestinal disorders | ||
| Diarrhea | 4/9 (44.4%) | 7 |
| Nausea | 4/9 (44.4%) | 4 |
| Constipation | 3/9 (33.3%) | 3 |
| Vomiting | 3/9 (33.3%) | 3 |
| Metabolism and nutrition disorders | ||
| Fatigue (asthenia, lethargy, malaise) | 6/9 (66.7%) | 14 |
| Creatinine | 2/9 (22.2%) | 2 |
| Nervous system disorders | ||
| Neuropathy: sensory | 2/9 (22.2%) | 2 |
| Renal and urinary disorders | ||
| AST, SGOT | 4/9 (44.4%) | 4 |
| Alkaline phosphatase | 4/9 (44.4%) | 4 |
| Proteinuria | 2/9 (22.2%) | 2 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Matthew Fury, MD |
|---|---|
| Organization | Memorial Sloan-Kettering Cancer Center |
| Phone | 646-888-4233 |
| furym@mskcc.org |
- NCI-2009-00192
- 06-074
- CDR0000559632
- N01CM62206
- NCT01645618
- NCT01664468