Phase II Study of Everolimus in Children and Adolescents With Refractory or Relapsed Rhabdomyosarcoma and Other Soft Tissue Sarcomas

The purpose of this study is to determine the Everolimus aim response in children and adolescents with refractory or relapsed Rhabdomyosarcoma and other soft tissue sarcomas

Study Overview

• Status: Unknown
• Conditions: Refractory or Relapsed RMS and Soft Tissue Sarcomas
• Intervention / Treatment: Drug: Everolimus

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sidnei Epelman, MD; Phone Number: +55 11 2522-2472; Email: pesquisaoncoped@santamarcelina.org

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 08270070
      • Recruiting
      • Casa de Saude Santa Marcelina
      • Contact: Sidnei Epelman, MD; Phone Number: +55 11 2522-2472; Email: pesquisaoncoped@santamarcelina.org
      • Principal Investigator: Sidnei Epelman, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Rhabdomyosarcoma and other soft tissue sarcoma histological confirmation.
• No option of known curative treatment, neither approved treatment that increases survival with adequate quality of life.
• Karnofsky scale ≥ 50 for patients over 16 years and Lansky scale ≥ 50 for patients under 16 years old.
• Subjects shouldn't have received antineoplasic therapy < 4 weeks before study treatment initiation.
• Adequate hematological function: neutrophil count > 1.500/mm³ and hemoglobin > 8.0 mg/dL.
• Adequate renal function, as defined below:

Age Maximum serum creatinine (mg/dL) 0 - 29 days 0,4 - 0,7 1 month - 3 years 0,7 4 - 7 years 0,8 8 - 10 years 0,9 11 - 12 years 1,0 13 - 17 years 1,2

≥ 18 years 1,3

• Adequate hepatic function: total bilirubin ≤ 1.5 x ULN.
• Patient and/or legal responsible must sign ICF.
• Life expectation > 8 weeks.
• Measurable disease, according to RECIST criteria.
• For female patients of childbearing age: presence of a negative pregnancy test within 7 days prior to day 0.
• The patient agrees to use effective contraception if procreative potential exists. Use of reliable means of contraception (e.g. hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier, abstinence)for subjects of reproductive potential (male and female) is required during study treatment and for 3 months following last dose of study drug.

Exclusion Criteria:

• History of myocardial infarction, angina and cerebrovascular accident related to atherosclerosis.
• Pulmonary disorder(e.g. FEV1 ou DLCO ≤ 70% from expected).
• Significant hematologic or hepatic abnormality (transaminases levels > 2.5 x ULN or serum bilirubin > 1.5 x ULN, hemoglobin < 8 g/dL, platelets < 100.000/mm³, ANC < 1.500/mm³.
• Has other existing serious medical conditions that could adversely affect the ability of the patient to be treated in accordance with the protocol.
• Any condition, therapy, or medical condition, which, in the opinion of the attending physician could represent a risk for the patient or adversely affect the study objectives.
• If female, is pregnant or lactating.
• Active infection at the moment of recruitment.
• Previous history of organ transplantation.
• Recent surgery < 2 months before entering study.
• Concomitant antineoplasic therapy.
• Patient received more than one rescue treatment, previously.
• Previous treatment with mTor inhibitors (ex: sirolimus, temsirolimus, everolimus).
• Use of investigational drug < 30 days before entering study.
• Non-controlled hyperlipidaemia: serum cholesterol (fasting) > 300 mg/dL or 7,75 mmol/L and triglycerides (fasting) > 2,5 x ULN.
• Non-controlled Diabetes Mellitus defined as: glycemia (fasting) > 1,5 x ULN.
• Patient with hemorrhagic disorder or using oral anti-vitamin K (except Warfarin in low doses).
• Patient with HIV infection.
• Incapable to perform protocol visits.
• Another neoplasia for the last 2 years (except squamous or basocellular skin cancer).
• Hypersensitivity history to rapamycin analogs.
• Chronic treatment with corticoids (except per oral, topical or local treatment) or another immunosuppressor agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Everolimus	Drug: Everolimus; Everolimus will be administered every day, initial dose 5 mg/m²/day, in 28 days cycle. Maximum dose: 10 mg/day. The cycles will be repeated till progression disease or untolerable toxicity.; Other Names: Afinitor, RAD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the Everolimus aim response in children and adolescents with refractory and relapsed Rhabdomyosarcoma and other soft tissue sarcomas	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Define Everolimus toxicity in this population	Up to 2 years

Collaborators and Investigators

• Sponsor: Sidnei Epelman

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): October 1, 2013
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: October 4, 2010
• First Submitted That Met QC Criteria: October 6, 2010
• First Posted (Estimate): October 7, 2010

Study Record Updates

• Last Update Posted (Estimate): March 26, 2013
• Last Update Submitted That Met QC Criteria: March 25, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue; Myosarcoma; Sarcoma; Rhabdomyosarcoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: CRAD001CBR08T

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No