Gemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma

NCT ID: NCT01684449

Last Updated: 2015-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-12-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 2: Experimental Arm

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).

Group Type: EXPERIMENTAL

Gemcitabine + Rapamycin

Intervention Type: 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.

Interventions

Gemcitabine + Rapamycin

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Age ≥ 18 y ≤ 70 years.

4. ECOG performance status: 0 - 1. In Phase 1 only patients with ECOG 0-1 will be enrolled.

5. Disease measurable according to RECIST criteria. Proven relapsed disease.

6. Adequate bone marrow function, defined as neutrophil count ≥ 1.500/mm^3 and platelets ≥ 100.000/mm^3.

7. 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).

8. Informed consent form signed by the patient prior to the beginning of the treatment.

Exclusion Criteria

1. History of previous cancer diagnosed or treated in the past 5 years except basal cell carcinoma, cervical carcinoma in situ or superficial bladder cancer.

2. Presence of brain metastases.

3. Active infection or other severe concomitant diseases.

4. Concurrent treatment with other experimental drugs within 30 days prior to study entry.

5. Pregnancy or breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Espanol de Investigacion en Sarcomas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier García del Muro Solans, MD

Role: STUDY_CHAIR

GEIS

Locations

H. Sant Pau

Barcelona, Barcelona, Spain

H. La Paz

Madrid, Madrid, Spain

H. Son Espases

Mallorca, Mallorca, Spain

H. Universitario de Canarias

Santa Cruz de Tenerife, Santa Cruz de Tenerife, Spain

Instituto Valenciano de Oncología

Valencia, Valencia, Spain

H. Universitario Miguel Servet

Zaragoza, Zaragoza, Spain

Institut Català d'Oncologia - Hospital Duran i Reynals

L'Hospitalet de Llobregat, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Majadahonda, , Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 29177953 (View on PubMed)

Other Identifiers

2009-017232-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GEIS-24

Identifier Type: -

Identifier Source: org_study_id