Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy (ONC-2010-001)
Primary Purpose
Thymoma and Thymic Carcinoma
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Thymoma and Thymic Carcinoma focused on measuring thymoma thymic carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histological diagnosis of invasive recurrent or metastatic thymoma or thymic carcinoma confirmed by pathologist.
- At least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received. Progressive disease should have been documented before entry into the study.
- Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral CT scan.
- Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by CTCAE 3.0).
- No major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study.
- Life expectancy of at least 3 months.
- Performance status (ECOG)<=2
- Negative pregnancy test (if female in reproductive years)
- Adequate organ and marrow function (as defined below)
- Leukocytes >=3,000/mm, Absolute neutrophil count >=1,500/mm, Hemoglobin>= 9 g/dL, Platelets>= 100,000/mm, Total bilirubin >= 1.5 x institutional upper limit of normal (ULN), AST(SGOT)/ALT(SGPT)>= 3 x institutional ULN (5x if LFT elevations due to liver metastases, )Creatinine <= 1.5 x institutional ULN
Exclusion Criteria:
- Patients with symptomatic brain metastases. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the investigator.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- Pregnant or breast feeding women
- Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
- Current enrollment in or participation in another therapeutic clinical trial within 4 weeks preceding treatment start.
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
Sites / Locations
- Istituto Clinico Humanitas
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Everolimus
Arm Description
oral everolimus
Outcomes
Primary Outcome Measures
disease control rate
disease control rate (DCR), considered as complete response (CR) plus partial response (PR) plus stable disease (SD), of Everolimus monotherapy
Secondary Outcome Measures
PFS
Progression free survival (PFS) will be evaluated from the date of treatment start until the date of progression or death whichever occurs first, otherwise until the last visit date.
Duration of Response
This endpoint is assessed in patients whose best tumor response is CR or PR as the time from the date of the first documentation of confirmed objective tumor response to the date of first documentation of objective tumor progression, objective tumor recurrence, or of death due progressive disease, whichever comes first
OS
Overall Survival (OS) will be evaluated from the date of treatment start until the date of death or last contact for patients alive at the end of the study.
FDG-PET imaging relations
To correlate response to therapy with changes in FDG-PET imaging at baseline and first restaging.
safety profile
Overall safety profile, evaluated on the basis of laboratory and clinical safety parameters
biomarkers expression
To perform immunohistochemistry for IGF-1R, pAKT ,mTOR, p-S6K, p-S6, p-4E-BP1, and pTEN expression in all pre-treatment tissue specimens of thymoma and thymic carcinoma and correlate with response and survival (PFS and OS).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02049047
Brief Title
Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy
Acronym
ONC-2010-001
Official Title
Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
February 2011 (Actual)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
January 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Armando Santoro, MD
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Given the high expression of IGF-1R and pAKT proteins in thymoma tissues, able to sensitize tumors to mTOR inhibition, and the anticancer activity of the mTOR inhibitors, clinical evaluation in thymoma and thymic carcinoma seems to be very interesting.
Patients will receive continuous treatment with oral everolimus 10 mg once daily.
Efficacy and safety profile of Everolimus will be evaluated.
Detailed Description
Patients will receive continuous treatment with oral everolimus 10 mg once daily. Study drug will be self-administered orally (two 5 mg tablets) daily in a fasting state or with a light fat-free meal. Each cycle will be considered as 21 days of treatment; safety was assessed every 21 days. Tumor assessement will be done every two cycles. Treatment should be administered until documented disease progression, unacceptable toxicity, or patient refusal.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thymoma and Thymic Carcinoma
Keywords
thymoma thymic carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
oral everolimus
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Intervention Description
Everolimus will be orally administered at the dosage of 10 mg once daily. Each cycle will be considered as 21 days of treatment. Tumor assessment will be done every two cycles.Treatment should be administered until documented disease progression, unacceptable toxicity, or patient refusal.
Primary Outcome Measure Information:
Title
disease control rate
Description
disease control rate (DCR), considered as complete response (CR) plus partial response (PR) plus stable disease (SD), of Everolimus monotherapy
Time Frame
6 months
Secondary Outcome Measure Information:
Title
PFS
Description
Progression free survival (PFS) will be evaluated from the date of treatment start until the date of progression or death whichever occurs first, otherwise until the last visit date.
Time Frame
6 months
Title
Duration of Response
Description
This endpoint is assessed in patients whose best tumor response is CR or PR as the time from the date of the first documentation of confirmed objective tumor response to the date of first documentation of objective tumor progression, objective tumor recurrence, or of death due progressive disease, whichever comes first
Time Frame
6 months
Title
OS
Description
Overall Survival (OS) will be evaluated from the date of treatment start until the date of death or last contact for patients alive at the end of the study.
Time Frame
6 months
Title
FDG-PET imaging relations
Description
To correlate response to therapy with changes in FDG-PET imaging at baseline and first restaging.
Time Frame
6 weeks
Title
safety profile
Description
Overall safety profile, evaluated on the basis of laboratory and clinical safety parameters
Time Frame
6 months
Title
biomarkers expression
Description
To perform immunohistochemistry for IGF-1R, pAKT ,mTOR, p-S6K, p-S6, p-4E-BP1, and pTEN expression in all pre-treatment tissue specimens of thymoma and thymic carcinoma and correlate with response and survival (PFS and OS).
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histological diagnosis of invasive recurrent or metastatic thymoma or thymic carcinoma confirmed by pathologist.
At least one prior platinum-containing chemotherapy regimen. There is no limit to the number of prior chemotherapy regimens received. Progressive disease should have been documented before entry into the study.
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than 20 mm with conventional techniques or as greater than 10 mm with spiral CT scan.
Patients must have recovered from toxicity related to prior therapy to at least to grade 1 (defined by CTCAE 3.0).
No major surgery, radiation therapy, chemotherapy, biologic therapy (including any investigational agents), or hormonal therapy (other than replacement), within 4 weeks prior to entering the study.
Life expectancy of at least 3 months.
Performance status (ECOG)<=2
Negative pregnancy test (if female in reproductive years)
Adequate organ and marrow function (as defined below)
Leukocytes >=3,000/mm, Absolute neutrophil count >=1,500/mm, Hemoglobin>= 9 g/dL, Platelets>= 100,000/mm, Total bilirubin >= 1.5 x institutional upper limit of normal (ULN), AST(SGOT)/ALT(SGPT)>= 3 x institutional ULN (5x if LFT elevations due to liver metastases, )Creatinine <= 1.5 x institutional ULN
Exclusion Criteria:
Patients with symptomatic brain metastases. However, patients who have had treatment for their brain metastases and whose brain metastatic disease status has remained stable for at least 3 months without steroids may be enrolled at the discretion of the investigator.
Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
Pregnant or breast feeding women
Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri
Current enrollment in or participation in another therapeutic clinical trial within 4 weeks preceding treatment start.
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Armando Santoro, MD
Organizational Affiliation
Istituto Clinico Humanitas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituto Clinico Humanitas
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
not planned
Citations:
PubMed Identifier
29240542
Citation
Zucali PA, De Pas T, Palmieri G, Favaretto A, Chella A, Tiseo M, Caruso M, Simonelli M, Perrino M, De Vincenzo F, Toffalorio F, Damiano V, Pasello G, Garbella E, Ali M, Conforti F, Ottaviano M, Cioffi A, De Placido S, Giordano L, Bertossi M, Destro A, Di Tommaso L, Santoro A. Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Cisplatin-Based Chemotherapy. J Clin Oncol. 2018 Feb 1;36(4):342-349. doi: 10.1200/JCO.2017.74.4078. Epub 2017 Dec 14.
Results Reference
derived
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Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy
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