Soft Tissue SarcomaPhase 1/2NCT00541840
Phase I-II Trial of Sorafenib in Combination With Ifosfamide in Soft Tissue Sarcoma
A Phase 1/2 study testing Sorafenib in people with Soft Tissue Sarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 1 site in Spain.
Trial summary
Soft tissue sarcomas (STS) are an uncommon group of malignant tumors of mesenchymal origin. For most advanced STS types, chemotherapy is currently the only available treatment. Unfortunately, a very limited number of useful drugs are active against this disease. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 24 participants
- Where
- 1 siteSpain
- Study dates
- Oct 2007to Apr 2010
- 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 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced Soft Tissue Sarcoma histologically proven, excluding the following subtypes: chondrosarcoma, osteosarcoma, Ewing's sarcoma, and embryonal rhabdomyosarcoma.
- Patients must have been previously treated with Anthracycline. However, patients not eligible for Anthracycline treatment can be included.Prior treatment with Ifosfamide is not allowed, except if it was administered as adjuvant therapy.
- Patients must be > 18 and < 72 years old.
- Patients must have ECOG performance status 0 to 1 on fase I.
- Patients must have ECOG performance status 0 to 2 on fase II.
- Patients must have measurable disease. Progression must be documented during the last month pre-study entry. No prior radiotherapy in the indicator lesion is allowed.
Show all 15Show fewer
- Adequate bone marrow, renal and hepatic function
- hemoglobin ³ 9.0 g/dl
- absolute neutrophil count ³ 1,500/mm3
- platelet count ³ 100,000/mm3
- total bilirubin £ 1.5 times the upper limit of normal
- ALT and AST £ 2.5 times the upper limit of normal (£ 5 x upper limit of normal for patients with liver involvement)
- INR £ 1.5 and aPTT within normal limits
- serum creatinine £ 1.5 the upper limit of normal
- Signed informed consent prior to any study specific procedures
Who cannot join
- Patients with previous chemotherapy or radiotherapy, within 3 weeks prior to study entry.
- Pregnant or breast feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
- Life expectancy of less than 12 weeks.
- General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
- Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study.
- Previous cancer that is distinct in primary site or histology from NSCLC except cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancer curatively treated > 3 years prior to study entry.
Show all 24Show fewer
- Concurrent treatment with other anti-cancer therapy.
- Concurrent treatment with other experimental drugs (within 30 days prior to study entry).
- Significant weight loss (> or equal 10% body weight during preceding 6 weeks).
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug.
- Biological modifying agents such as G-CSF administered within 3 weeks prior to study entry.
- Known or suspected allergy to sorafenib or ifosfamide.
- Evidence or history of bleeding diathesis or coagulopathy.
- Therapeutic anticoagulation with Vitamin K antagonists such as warfarin or with heparins or heparinoids. Low dose warfarin is permitted if INR is <1.5. Low dose aspirin is permitted.
- Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal medical management.
- Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina or new-onset angina (began within the last 3 months) or myocardial infarction within the last 6 months.
- Active clinically serious infections > CTCAE Grade 2.
- Serious, non-healing wound, ulcer, or bone fracture.
- Concomitant treatment with ketoconazole, itraconazole, ritonavir, rifampicin and St. John´s Wort.
- Known HIV infection or chronic hepatitis B or C.
- Known brain metastasis. Patients with neurological symptoms should undergo a CT scan/MRI of the brain to exclude brain metastasis.
- Any other condition that could compromise patient's security and/or study's fulfilment.
- Known or suspected allergy to mesna or tiolic agents.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Grupo Geis
Madrid, Madrid, 28001
Xavier Garcia del Muro, MD, 915775281, info@grupogeis.org
Xavier Garcia del Muro, MD
About this study
Official title: Phase I-II, Not-Randomized, Multicenter Clinical Trial to Evaluate Safety and Efficacy of Sorafenib (BAY-43-9006) in Combination With Ifosfamide in Soft Tissue Sarcoma.
Soft tissue sarcomas (STS) are an uncommon group of malignant tumors of mesenchymal origin. For most advanced STS types, chemotherapy is currently the only available treatment. Unfortunately, a very limited number of useful drugs are active against this disease. Doxorubicin is widely considered the standard first-line treatment. Ifosfamide has also a well-established activity (1,2) and is often administered either associated with Doxorubicin or alone as a second-line chemotherapy treatment. Other drugs such as DTIC, Gemcitabine and Temozolomide showed modest activity as a second-line agents (3,4). Thus, there is a necessity to identify new agents with activity to improve therapy for patients with advanced STS. In some studies, most STS showed VEGF expression, and elevated serum VEGF levels were found to correlate with higher histologic tumor grade (5,6). Additionally, inhibition of VEGFR was associated with tumor activity in preclinical models of sarcoma (7,8). For these reasons, inhibition of VEGFR seems to be a reasonable approach to explore in the treatment of STS. Sorafenib (BAY 43-9006) is an orally available, small molecule multi-kinase inhibitor of VEGFR, PDGFR and RAF with demonstrated activity in the treatment of renal cell cancer (9). Preclinical studies suggest that the combination of Sorafenib with cytotoxic agents results in additive anti-tumor activity (10), initiating justification for combination studies. A recent trial, however, reported an unexpected incidence of cardiac toxicity in patients with STS treated with Bevacizumab, a monoclonal antibody that binds VEGF, in combination with Doxorubicin (11). This finding suggest that the possibility of potentiation of the cardiotoxicity of Doxorubicin when inhibiting the VEGF pathway cannot be ruled out. The association of Sorafenib with Ifosfamide, the other established active agent against STS, could improve the efficacy of single-agent Ifosfamide minimizing the risk of cardiac toxicity .
- Conditions
- Soft Tissue Sarcoma
- Being tested
- Sorafenib
- Keywords
- Sarcoma, Sorafenib, GEIS
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called BAY 43-9006
Phase I:
Level 1: Sorafenib 200 mg bid, orally Ifosfamide 2,0 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 400 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration
Level 2: Sorafenib 400 mg bid, orally Ifosfamide 2.00 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 400 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration
Level 3 : Sorafenib 400mg bid, orally Ifosfamide 2.5 g/m2 , intravenously , over 4 hours , on 3 consecutive days . Mesna 500mg/m2,iv,at 0,4 and 8 hours after ifosfamide administration .
Level 4 : Sorafenib 400 mg bid, orally Ifosfamide 3.0 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 600 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration
Phase II:
Sorafenib and Ifosfamide administered at the doses recommended in phase I until progression or unacceptable toxicity.
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Ifosfamide. Phase II: Activity profile evaluating of the combination in patients with advanced soft tissue sarcoma.
Measured: Phase II: Progression free rate: at 3 and 6 months
Secondary outcomes (1)
Phase II: Efficacy evaluation
Measured: Phase II: Progression free rate at 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2007 (estimated)
- Study startOct 2007
- Primary completionApr 2009 (estimated)
- Study completionApr 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Investigacion en Sarcomas
- Sponsor type
- University, hospital or other
- Investigators
- Xavier Garcia del Muro, MD, Study director, Grupo Español de Investigacion en Sarcomas (GEIS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00541840
- Sponsor's protocol ID
- GEIS01-07
- Status last verified
- May 2008
- First submitted
- 9 Oct 2007
- Last updated
- 12 May 2008
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I-II, Not-Randomized, Multicenter Clinical Trial to Evaluate Safety and Efficacy of Sorafenib (BAY-43-9006) in Combination With Ifosfamide in Soft Tissue Sarcoma.
- ClinicalTrials.gov ID
- NCT00541840
- Acronym / sponsor ID
- GEIS01-07
- Conditions
- Soft Tissue Sarcoma
- Keywords
- Sarcoma, Sorafenib, GEIS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Grupo Espanol de Investigacion en SarcomasUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Apr 2009 (estimated)
- Study completion
- Apr 2010 (estimated)
- First posted
- 10 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Soft tissue sarcomas (STS) are an uncommon group of malignant tumors of mesenchymal origin. For most advanced STS types, chemotherapy is currently the only available treatment. Unfortunately, a very limited number of useful drugs are active against this disease. Doxorubicin is widely considered the standard first-line treatment. Ifosfamide has also a well-established activity (1,2) and is often administered either associated with Doxorubicin or alone as a second-line chemotherapy treatment. Other drugs such as DTIC, Gemcitabine and Temozolomide showed modest activity as a second-line agents (3,4). Thus, there is a necessity to identify new agents with activity to improve therapy for patients with advanced STS. In some studies, most STS showed VEGF expression, and elevated serum VEGF levels were found to correlate with higher histologic tumor grade (5,6). Additionally, inhibition of VEGFR was associated with tumor activity in preclinical models of sarcoma (7,8). For these reasons, inhibition of VEGFR seems to be a reasonable approach to explore in the treatment of STS. Sorafenib (BAY 43-9006) is an orally available, small molecule multi-kinase inhibitor of VEGFR, PDGFR and RAF with demonstrated activity in the treatment of renal cell cancer (9). Preclinical studies suggest that the combination of Sorafenib with cytotoxic agents results in additive anti-tumor activity (10), initiating justification for combination studies. A recent trial, however, reported an unexpected incidence of cardiac toxicity in patients with STS treated with Bevacizumab, a monoclonal antibody that binds VEGF, in combination with Doxorubicin (11). This finding suggest that the possibility of potentiation of the cardiotoxicity of Doxorubicin when inhibiting the VEGF pathway cannot be ruled out. The association of Sorafenib with Ifosfamide, the other established active agent against STS, could improve the efficacy of single-agent Ifosfamide minimizing the risk of cardiac toxicity .
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Advanced Soft Tissue Sarcoma histologically proven, excluding the following subtypes: chondrosarcoma, osteosarcoma, Ewing's sarcoma, and embryonal rhabdomyosarcoma.
- Patients must have been previously treated with Anthracycline. However, patients not eligible for Anthracycline treatment can be included.Prior treatment with Ifosfamide is not allowed, except if it was administered as adjuvant therapy.
- Patients must be > 18 and < 72 years old.
- Patients must have ECOG performance status 0 to 1 on fase I.
- Patients must have ECOG performance status 0 to 2 on fase II.
Key exclusion criteria (24 listed)
- Patients with previous chemotherapy or radiotherapy, within 3 weeks prior to study entry.
- Pregnant or breast feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
- Life expectancy of less than 12 weeks.
- General medical or psychological conditions that would preclude appropriate informed consent or compliance with the protocol.
- Substance abuse, medical, psychological or social conditions that may interfere with the patients participation in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibAlso: BAY 43-9006Phase I: Level 1: Sorafenib 200 mg bid, orally Ifosfamide 2,0 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 400 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration Level 2: Sorafenib 400 mg bid, orally Ifosfamide 2.00 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 400 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration Level 3 : Sorafenib 400mg bid, orally Ifosfamide 2.5 g/m2 , intravenously , over 4 hours , on 3 consecutive days . Mesna 500mg/m2,iv,at 0,4 and 8 hours after ifosfamide administration . Level 4 : Sorafenib 400 mg bid, orally Ifosfamide 3.0 g/m2, intravenously, over 4 hours, on 3 consecutive days Mesna 600 mg/m2 iv, at 0, 4 and 8 hours after the Ifosfamide administration Phase II: Sorafenib and Ifosfamide administered at the doses recommended in phase I until progression or unacceptable toxicity. | Drug | – |
Primary outcome
Phase I: Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Ifosfamide. Phase II: Activity profile evaluating of the combination in patients with advanced soft tissue sarcoma.
Time frame: Phase II: Progression free rate: at 3 and 6 months
1 secondary outcome
Phase II: Efficacy evaluation
Time frame: Phase II: Progression free rate at 3 and 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2008.
- Grupo Español de Investigacion en Sarcomas WebsiteLink provided by the sponsor.
Related trials for Soft Tissue Sarcoma
RecruitingPhase 2
A Multicenter Phase II Clinical Trial Evaluating 68Ga-HX01 Injection for PET/CT Imaging
Soft Tissue Sarcoma
RecruitingPhase 3
Measuring if Immunotherapy Plus Chemotherapy is Better Than Chemotherapy Alone for Patients With Aggressive Poorly Differentiated Sarcomas
Metastatic Dedifferentiated Liposarcoma, Metastatic Undifferentiated Pleomorphic Sarcoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Enrolling by invitationPhase 1
Evaluation of the I-phase Clinical Trial of 177Lu-HX02 Injection in Patients With Advanced Malignant Solid Tumors
Soft Tissue Sarcoma, Non-small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xavier Garcia del Muro, MD study director
Grupo Español de Investigacion en Sarcomas (GEIS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sorafenib in people with Soft Tissue Sarcoma, run by Grupo Espanol de Investigacion en Sarcomas at 1 site 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 15 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 12 May 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xavier Garcia del Muro, MD (93 260 73 32, garciadelmuro@ico.scs.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Safety profile and to determine maximum tolerated dose (MTD) / Recommended Dose (DR) of Sorafenib in combination with Ifosfamide. Phase II: Activity profile evaluating of the combination in patients with advanced soft tissue sarcoma. (time frame: Phase II: Progression free rate: at 3 and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2008.