Clinical trial NCT00718809: Saracatinib in Treating Patients With Relapsed or Refractory Thymoma or Thymic Cancer
Official title: Phase II Trial of AZD0530 for Patients With Relapsed/Refractory Thymic Malignancies (Thymoma and Thymic Carcinoma)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Invasive Thymoma and Thymic Carcinoma
Recurrent Thymoma and Thymic Carcinoma
Stage III Thymoma
Stage IVA Thymoma
Stage IVB Thymoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-07-21
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well saracatinib works in treating patients with relapsed or refractory thymoma or thymic cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (complete response and partial response) in patients with relapsed or refractory thymoma or thymic carcinoma treated with AZD0530.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of AZD0530 in these patients. II. To evaluate the progression-free survival of these patients. III. To evaluate the overall survival of these patients. IV. To evaluate the disease control rate, defined as complete response, partial response, and stable disease, in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral saracatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive thymoma or thymic carcinoma, meeting the following criteria:

  * Relapsed or refractory disease
  * Metastatic, unresectable disease
  * Locally invasive disease allowed provided it is not resectable and has been previously treated
  * Progressive disease
* Measurable disease, defined as \>= 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques or \>= 10 mm by spiral CT scan
* Must have received \>= 1 prior chemotherapy regimen
* No active brain metastases
* Patients with previously treated brain metastases (surgical resection or radiotherapy) are eligible provided they have documented stable brain disease for \>= 1 month after completion of therapy and are asymptomatic
* ECOG performance status 0-2
* Leukocytes \>= 3,000/mm\^3
* ANC \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \> 9 g/dL
* Serum bilirubin \< 2.0 times upper limit of normal (ULN)
* Transaminases =\< 2.5 times ULN (\< 5.0 times ULN if liver metastasis is present)
* Serum creatinine \< 1.5 times ULN OR creatinine clearance \> 50 mL/min
* Urine protein:creatinine ratio \< 0.5 OR urine protein \< 1,000 mg by 24-hour urine collection
* QTc \< 460 msec
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 30 days after completion of study treatment
* No known history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
* No other malignancies within the past 3 years, except curatively treated in situ carcinoma of the cervix or completely resected nonmelanoma skin cancer
* No concurrent active malignancies other than thymic malignancy
* No condition that impairs the ability to swallow AZD0350 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
* No cardiac dysfunction including, but not limited to, any of the following:

  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * History of ischemic heart disease
  * Myocardial infarction within the past year
  * No QTc prolongation or other significant ECG abnormalities
  * No poorly controlled hypertension (i.e., systolic blood pressure \[BP\] ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg)
* No evidence of severe or uncontrolled systemic conditions that would make it undesirable to participate in the study or that would jeopardize compliance with the study, including any of the following:

  * Severe hepatic impairment
  * Interstitial lung disease (bilateral, diffuse, or parenchymal lung disease)
  * Unstable or uncompensated respiratory condition
  * Unstable or uncompensated cardiac condition
* No uncontrolled illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Mental health issues or social circumstances that would limit compliance with study requirements
* No prior src inhibitors
* At least 4 weeks since prior systemic therapy (6 weeks for carmustine or mitomycin C)
* At least 8 weeks since prior immunotherapy
* At least 4 weeks since prior octreotide
* Concurrent octreotide for pure red cell aplasia allowed provided patient continues on the same dose and schedule, has had a response to this drug, and has demonstrated progressive thymoma by radiography or physical exam
* At least 4 weeks since prior surgery and recovered
* At least 4 weeks since prior investigational agents
* At least 4 weeks since prior radiotherapy to measurable disease sites (2 weeks for palliative radiotherapy to metastatic sites) and recovered
* At least 7 days since prior and no concurrent active CYP3A4 agents or substances
* No other concurrent investigational or anticancer agents
* No concurrent combination antiretroviral therapy for HIV-positive patients
* Concurrent steroids allowed for treatment of a pre-existing autoimmune disorder or as antiemetic therapy

Primary outcomes:
measure: Objective Response Rate (Complete and Partial Response)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: Time from the date of registration to the first reported outcome event, assessed up to 5 years
measure: Overall Survival
timeFrame: Time from the date of registration to last reported date of survival, assessed up to 5 years
measure: Disease Control Rate
timeFrame: Up to 5 years
measure: Expected Toxicities Including Skin Rashes and Diarrhea
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Hospitals and Clinics
state: California
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Patrick Loehrer
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gubens MA, Burns M, Perkins SM, Pedro-Salcedo MS, Althouse SK, Loehrer PJ, Wakelee HA. A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies. Lung Cancer. 2015 Jul;89(1):57-60. doi: 10.1016/j.lungcan.2015.04.008. Epub 2015 Apr 25.