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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Istituto Clinico Humanitas
Sponsor:
Information provided by (Responsible Party):
Armando Santoro, MD, Istituto Clinico Humanitas
ClinicalTrials.gov Identifier:
NCT02049047
First received: May 27, 2013
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Thymoma and Thymic Carcinoma
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Everolimus in Patients With Thymoma and Thymic Carcinoma Previously Treated With Chemotherapy

Resource links provided by NLM:


Further study details as provided by Istituto Clinico Humanitas:

Primary Outcome Measures:
  • disease control rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    disease control rate (DCR), considered as complete response (CR) plus partial response (PR) plus stable disease (SD), of Everolimus monotherapy


Secondary Outcome Measures:
  • PFS [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    To correlate response to therapy with changes in FDG-PET imaging at baseline and first restaging.

  • safety profile [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Overall safety profile, evaluated on the basis of laboratory and clinical safety parameters

  • biomarkers expression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 41
Study Start Date: February 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02049047

Contacts
Contact: Armando Santoro, MD +39 (0)2 8224 ext 4080 armando.santoro@humanitas.it
Contact: Paolo A. Zucali, MD +39 (0)2 8224 ext 4061 paolo.zucali@humanitas.it

Locations
Italy
Istituto Clinico Humanitas Recruiting
Rozzano, MI, Italy, 20089
Contact: Armando Santoro, MD    +39 (0)2 8224 ext 4080    armando.santoro@humanitas.it   
Contact: Paolo A. Zucali, MD    +39 (0)2 8224 ext 4061    paolo.zucali@humanitas.it   
Principal Investigator: Armando Santoro, MD         
Sub-Investigator: Paolo A. Zucali, MD         
Sponsors and Collaborators
Armando Santoro, MD
Investigators
Principal Investigator: Armando Santoro, MD Istituto Clinico Humanitas
  More Information

No publications provided

Responsible Party: Armando Santoro, MD, principal Investigator, Istituto Clinico Humanitas
ClinicalTrials.gov Identifier: NCT02049047     History of Changes
Other Study ID Numbers: ONC-2010-001
Study First Received: May 27, 2013
Last Updated: February 6, 2014
Health Authority: Italy: Ministry of Health

Keywords provided by Istituto Clinico Humanitas:
thymoma thymic carcinoma

Additional relevant MeSH terms:
Thymoma
Thymus Neoplasms
Carcinoma
Lymphatic Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Glandular and Epithelial
Thoracic Neoplasms
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014