Back to resultsGemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma
Primary Purpose
Advanced Soft Tissue Sarcoma
Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
Gemcitabine + Rapamycin
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Soft Tissue Sarcoma focused on measuring Soft tissue sarcoma, Gemcitabine, Rapamycin, Sirolimus, mTOR inhibitor, Molecular biomarkers
Eligibility Criteria
Inclusion Criteria:
- Patients with anatomopathological diagnosis of metastatic or locally advanced unresectable soft tissue sarcoma (STS). Patients with the following STS types will be excluded: chondrosarcoma, Ewing's sarcoma and embryonal or alveolar rhabdomyosarcoma. In phase 1 it will be allowed to include patients having other types of advanced cancer which are resistant to the standard treatment and can benefit from any of the study drugs.
- Prior treatment with chemotherapy including doxorubicin and ifosfamide, or contraindication for its administration. The previous treatment with gemcitabine or inhibitors of mTOR is not allowed.
- Age ≥ 18 y ≤ 70 years.
- ECOG performance status: 0 - 1. In Phase 1 only patients with ECOG 0-1 will be enrolled.
- Disease measurable according to RECIST criteria. Proven relapsed disease.
- Adequate bone marrow function, defined as neutrophil count ≥ 1.500/mm^3 and platelets ≥ 100.000/mm^3.
- Adequate renal and hepatic function , defined as calculated creatinine clearance ≥ 60 ml/min, creatinine, total bilirubin, AST and/or ALT ≤ 1,5 times the upper limit of normal (ULN).
- Informed consent form signed by the patient prior to the beginning of the treatment.
Exclusion Criteria:
- History of previous cancer diagnosed or treated in the past 5 years except basal cell carcinoma, cervical carcinoma in situ or superficial bladder cancer.
- Presence of brain metastases.
- Active infection or other severe concomitant diseases.
- Concurrent treatment with other experimental drugs within 30 days prior to study entry.
- Pregnancy or breastfeeding.
Sites / Locations
- H. Universitario de Canarias
- H. Sant Pau
- Institut Català d'Oncologia - Hospital Duran i Reynals
- H. La Paz
- Hospital Universitario 12 de Octubre
- Hospital Universitario Puerta de Hierro
- H. Son Espases
- Instituto Valenciano de Oncología
- H. Universitario Miguel Servet
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Phase 2: Experimental Arm
Arm Description
Gemcitabine + rapamycin at recommended dose of Phase 1. Recommended dose is defined as, the dose one level below of the (MTD). Being MTD, the dose of the cohort in which a maximum of one patient of 6 has presented dose-limiting toxicity (DLT).
Outcomes
Primary Outcome Measures
Phase 1: Determination of dosage: Security and toxicity of the combination gemcitabine and rapamycin.
Type, frequency, seriousness and relation with the treatment of the adverse events in patients treated with the investigational medicinal products.
Phase 2: Progression Free Survival
Progression free survival rate at 3 months to compare the effectiveness of the the treatment.
Secondary Outcome Measures
Phase 2: Overall Survival
Overall survival rate of the patients included in the experimental arm.
Phase 2: Toxicity
Tolerance to the drugs combination of the patients treated with gemcitabine + sirolimus
Phase 1 and 2: Assessment of molecular biomarkers
Assess, both in models of sarcomas induced in immunodeficient mice and tumor samples from patients enrolled in the trial, the predictive value of the response to combination therapy of certain molecular markers for survival and mTOR pathway.
Full Information
NCT ID
NCT01684449
First Posted
June 30, 2011
Last Updated
October 26, 2015
Sponsor
Grupo Espanol de Investigacion en Sarcomas
1. Study Identification
Unique Protocol Identification Number
NCT01684449
Brief Title
Gemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma
Official Title
Phase 1/2, Randomized, Multicenter, Prospective Study of Gemcitabine and Rapamycin (Sirolimus) Combination Versus Gemcitabine Only to Treat Advanced Soft Tissue Sarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo Espanol de Investigacion en Sarcomas
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The soft tissue sarcomas (STS) constitute an infrequent group of malignant neoplasms of mesenchymal origin. In Spain, the approximate incidence is of 2 new cases per 100.000 inhabitants every year. In patients with metastatic STS, the average survival is very short, approximately 12 months. The systemic treatment of the metastatic disease has had a very limited development, with few satisfactory results. This facts reflect the urgent need to identify new active agents for treatment of these patients.
The molecular pathway of the serine/threonine kinase mammalian target of rapamycin (mTOR) plays a central role in the regulation of the proteins translation, cellular growth and metabolism (Meric-Bernstam F et al. 2009). Currently, the mTOR pathway is considered a relevant target for the development of anti-cancer drugs, as rapamycin. Preliminary results of some clinical trials suggest that mTOR inhibitors could have some clinical activity for different types of sarcoma, including STS (Chawla et al Proc.ASCO 2006; Schuetze et al. Proc.ASCO 2006).
Gemcitabine is a chemotherapy antimetabolite agent with a broad antitumoral spectrum. The activity of this drug to treat resistant sarcomas and its reduced toxicity make from gemcitabine an adequate candidate for its study in combination with new drugs addressed to molecular targets in the STS treatment.
Pre-clinical studies suggest that mTOR inhibitors could have a potential synergistic or additive effect with some chemotherapy agents. The combination of rapamycin and gemcitabine seems to be a reasonable strategy to explore for the STS treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Soft Tissue Sarcoma
Keywords
Soft tissue sarcoma, Gemcitabine, Rapamycin, Sirolimus, mTOR inhibitor, Molecular biomarkers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 2: Experimental Arm
Arm Type
Experimental
Arm Description
Gemcitabine + rapamycin at recommended dose of Phase 1. Recommended dose is defined as, the dose one level below of the (MTD). Being MTD, the dose of the cohort in which a maximum of one patient of 6 has presented dose-limiting toxicity (DLT).
Intervention Type
Drug
Intervention Name(s)
Gemcitabine + Rapamycin
Intervention Description
Gemcitabine + rapamycin at recommended dose of Phase 1. Recommended dose is defined as, the dose one level below of the (MTD). Being MTD, the dose of the cohort in which a maximum of one patient of 6 has presented dose-limiting toxicity (DLT).
Every three weeks until disease progression or unacceptable toxicity. The treatment will last for 6 cycles if there is not progression or intolerable toxicity.
Additionally, there will be a pharmacokinetic study in a minimum of 9 patients treated with the drug combination.
Primary Outcome Measure Information:
Title
Phase 1: Determination of dosage: Security and toxicity of the combination gemcitabine and rapamycin.
Description
Type, frequency, seriousness and relation with the treatment of the adverse events in patients treated with the investigational medicinal products.
Time Frame
15 months
Title
Phase 2: Progression Free Survival
Description
Progression free survival rate at 3 months to compare the effectiveness of the the treatment.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Phase 2: Overall Survival
Description
Overall survival rate of the patients included in the experimental arm.
Time Frame
12 months
Title
Phase 2: Toxicity
Description
Tolerance to the drugs combination of the patients treated with gemcitabine + sirolimus
Time Frame
12 months
Title
Phase 1 and 2: Assessment of molecular biomarkers
Description
Assess, both in models of sarcomas induced in immunodeficient mice and tumor samples from patients enrolled in the trial, the predictive value of the response to combination therapy of certain molecular markers for survival and mTOR pathway.
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with anatomopathological diagnosis of metastatic or locally advanced unresectable soft tissue sarcoma (STS). Patients with the following STS types will be excluded: chondrosarcoma, Ewing's sarcoma and embryonal or alveolar rhabdomyosarcoma. In phase 1 it will be allowed to include patients having other types of advanced cancer which are resistant to the standard treatment and can benefit from any of the study drugs.
Prior treatment with chemotherapy including doxorubicin and ifosfamide, or contraindication for its administration. The previous treatment with gemcitabine or inhibitors of mTOR is not allowed.
Age ≥ 18 y ≤ 70 years.
ECOG performance status: 0 - 1. In Phase 1 only patients with ECOG 0-1 will be enrolled.
Disease measurable according to RECIST criteria. Proven relapsed disease.
Adequate bone marrow function, defined as neutrophil count ≥ 1.500/mm^3 and platelets ≥ 100.000/mm^3.
Adequate renal and hepatic function , defined as calculated creatinine clearance ≥ 60 ml/min, creatinine, total bilirubin, AST and/or ALT ≤ 1,5 times the upper limit of normal (ULN).
Informed consent form signed by the patient prior to the beginning of the treatment.
Exclusion Criteria:
History of previous cancer diagnosed or treated in the past 5 years except basal cell carcinoma, cervical carcinoma in situ or superficial bladder cancer.
Presence of brain metastases.
Active infection or other severe concomitant diseases.
Concurrent treatment with other experimental drugs within 30 days prior to study entry.
Pregnancy or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xavier García del Muro Solans, MD
Organizational Affiliation
GEIS
Official's Role
Study Chair
Facility Information:
Facility Name
H. Universitario de Canarias
City
Tenerife
State/Province
Santa Cruz de Tenerife
ZIP/Postal Code
38320
Country
Spain
Facility Name
H. Sant Pau
City
Barcelona
ZIP/Postal Code
08024
Country
Spain
Facility Name
Institut Català d'Oncologia - Hospital Duran i Reynals
City
L'Hospitalet de Llobregat
Country
Spain
Facility Name
H. La Paz
City
Madrid
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Puerta de Hierro
City
Majadahonda
Country
Spain
Facility Name
H. Son Espases
City
Mallorca
Country
Spain
Facility Name
Instituto Valenciano de Oncología
City
Valencia
Country
Spain
Facility Name
H. Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
29177953
Citation
Martin-Liberal J, Lopez-Pousa A, Martinez-Trufero J, Martin-Broto J, Cubedo R, Lavernia J, Redondo A, Lopez-Martin JA, Mulet-Margalef N, Sanjuan X, Tirado OM, Garcia-Del-Muro X. Phase II Study of Gemcitabine Plus Sirolimus in Previously Treated Patients with Advanced Soft-Tissue Sarcoma: a Spanish Group for Research on Sarcomas (GEIS) Study. Target Oncol. 2018 Feb;13(1):81-87. doi: 10.1007/s11523-017-0539-9.
Results Reference
derived
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Gemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma
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