Gemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma

NCT01684449 | Completed Phase 1 DMC

• 2 other identifiers: GEIS-242009-017232-41
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 9

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.

Conditions

Advanced Soft Tissue Sarcoma

Keywords

Soft tissue sarcoma; Gemcitabine; Rapamycin; Sirolimus; mTOR inhibitor; Molecular biomarkers

Outcome Measures

Primary Outcomes (2)

• 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.

  15 months

• Phase 2: Progression Free Survival

  Progression free survival rate at 3 months to compare the effectiveness of the the treatment.

  12 months

Secondary Outcomes (3)

• Phase 2: Overall Survival

  12 months

• Phase 2: Toxicity

  12 months

• Phase 1 and 2: Assessment of molecular biomarkers

  36 months

Study Arms (1)

Phase 2: Experimental Arm

EXPERIMENTAL

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).

Drug: Gemcitabine + Rapamycin

Interventions

Gemcitabine + Rapamycin DRUG

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.

Phase 2: Experimental Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (9)

H. Sant Pau

Barcelona, Barcelona, 08024, Spain

Location

H. La Paz

Madrid, Madrid, Spain

Location

H. Son Espases

Mallorca, Mallorca, Spain

Location

H. Universitario de Canarias

Santa Cruz de Tenerife, Santa Cruz de Tenerife, 38320, Spain

Location

Instituto Valenciano de Oncología

Valencia, Valencia, Spain

Location

H. Universitario Miguel Servet

Zaragoza, Zaragoza, 50009, Spain

Location

Institut Català d'Oncologia - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Related Publications (1)

• 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.

  PMID: 29177953 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Gemcitabine; Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Macrolides; Lactones; Organic Chemicals

Study Officials

• Xavier García del Muro Solans, MD

  GEIS

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: September 13, 2012
• Study Start: January 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 27, 2015

Record last verified: 2015-10

Locations

ES (9)