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Advanced Soft Tissue SarcomaPhase 1/2NCT01684449

Gemcitabine Plus Rapamycin Versus Gemcitabine to Treat Advanced Soft Tissue Sarcoma

A Phase 1/2 study testing Gemcitabine + Rapamycin in people with Advanced Soft Tissue Sarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 9 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Advanced Soft Tissue Sarcoma
What is being tested?
Gemcitabine + Rapamycin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
9 sitesSpain
Study dates
Jan 2010to Dec 2013
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Spain9 sites

  • H. Sant Pau

    Barcelona, Barcelona, 08024

  • Institut Català d'Oncologia - Hospital Duran i Reynals

    L'Hospitalet de Llobregat

  • H. La Paz

    Madrid, Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario Puerta de Hierro

    Majadahonda

  • H. Son Espases

    Mallorca, Mallorca

  • H. Universitario de Canarias

    Santa Cruz de Tenerife, Santa Cruz de Tenerife, 38320

  • Instituto Valenciano de Oncología

    Valencia, Valencia

  • H. Universitario Miguel Servet

    Zaragoza, Zaragoza, 50009

Other trials in Spain

About this study

Official title: Phase 1/2, Randomized, Multicenter, Prospective Study of Gemcitabine and Rapamycin (Sirolimus) Combination Versus Gemcitabine Only to Treat Advanced Soft Tissue Sarcoma

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).

Read more

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.

Being tested
Gemcitabine + Rapamycin
Keywords
Soft tissue sarcoma, Gemcitabine, Rapamycin, Sirolimus, mTOR inhibitor, Molecular biomarkers
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gemcitabine + RapamycinDrug

    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.

Study groups in NCT01684449
Study groupRoleWhat they receive
Phase 2: Experimental ArmExperimentalGemcitabine + 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).
Receives: Drug: Gemcitabine + Rapamycin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 15 months

  2. Phase 2: Progression Free Survival

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

    Measured: 12 months

Secondary outcomes (3)

  1. Phase 2: Overall Survival

    Overall survival rate of the patients included in the experimental arm.

    Measured: 12 months

  2. Phase 2: Toxicity

    Tolerance to the drugs combination of the patients treated with gemcitabine + sirolimus

    Measured: 12 months

  3. 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.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2012 (estimated)
  2. Study startJan 2010
  3. Primary completionMay 2013
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01684449
Sponsor's protocol ID
GEIS-24
Other IDs
2009-017232-41, 2009
Status last verified
Oct 2015
First submitted
30 Jun 2011
Last updated
27 Oct 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29177953

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Gemcitabine + Rapamycin in people with Advanced Soft Tissue Sarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 9 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Determination of dosage: Security and toxicity of the combination gemcitabine and rapamycin. (time frame: 15 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01684449, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2015.

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