Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy (ONC-2010-001)

• ClinicalTrials.gov Identifier: NCT02049047
• Recruitment Status: Completed
• First Posted: January 29, 2014
• Last Update Posted: January 22, 2021
• Sponsor: Armando Santoro, MD
• Information provided by (Responsible Party): Armando Santoro, MD, Istituto Clinico Humanitas

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.

Condition or disease	Intervention/treatment	Phase
Thymoma and Thymic Carcinoma	Drug: Everolimus	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy
• Actual Study Start Date: February 2011
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: January 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Everolimus; oral everolimus	Drug: Everolimus; 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.; Other Name: Afinitor

Outcome Measures

Primary Outcome Measures :

1. disease control rate [ Time Frame: 6 months ]
   disease control rate (DCR), considered as complete response (CR) plus partial response (PR) plus stable disease (SD), of Everolimus monotherapy

Secondary Outcome Measures :

1. PFS [ Time Frame: 6 months ]
   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.
2. Duration of Response [ Time Frame: 6 months ]
   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
3. OS [ Time Frame: 6 months ]
   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.
4. FDG-PET imaging relations [ Time Frame: 6 weeks ]
   To correlate response to therapy with changes in FDG-PET imaging at baseline and first restaging.
5. safety profile [ Time Frame: 6 months ]
   Overall safety profile, evaluated on the basis of laboratory and clinical safety parameters
6. biomarkers expression [ Time Frame: 6 months ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Italy

Istituto Clinico Humanitas

Rozzano, MI, Italy, 20089

Sponsors and Collaborators

Armando Santoro, MD

Investigators

• Principal Investigator: Armando Santoro, MD; Istituto Clinico Humanitas

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Armando Santoro, MD, principal Investigator, Istituto Clinico Humanitas
• ClinicalTrials.gov Identifier: NCT02049047
• Other Study ID Numbers: ONC-2010-001
• First Posted: January 29, 2014
• Last Update Posted: January 22, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: not planned

Keywords provided by Armando Santoro, MD, Istituto Clinico Humanitas:

thymoma thymic carcinoma

Additional relevant MeSH terms:

Carcinoma; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Complex and Mixed; Thoracic Neoplasms; Neoplasms by Site; Lymphatic Diseases; Everolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs