Metastatic Breast CancerPhase 2PASONCT01320111
Breast Cancer Study: Paclitaxel Versus Paclitaxel Plus Sorafenib in Second- or Third-line Treatment
A Phase 2 study testing Paclitaxel and Sorafenib and Paclitaxel in people with Metastatic Breast Cancer, run by Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH at 1 site in Germany.
Trial summary
AIM OF STUDY Primary Efficacy Variable: The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Paclitaxel and Sorafenib and Paclitaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jul 2010to 31 Aug 2014
- Phase
- Phase 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed adenocarcinoma of the breast
- HER-2/neu negative (primary tumour site HER-2/neu negative by ICH/FISH test)
- Second till third-line of chemotherapy
- Female, age ≥ 18 years.
- ECOG Performance Status of 0 or 1 (Karnofsky-Index ≥ 70%)
- Life expectancy of at least 12 weeks.
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- Subjects with at least one uni-dimensional (for RECIST 1.1) measurable lesion. Lesions must be measured by Xray (pulmonary lesions only) or CT-scan or MRI (Patients with only measurable bone lesions can be also included, as long they meet the criteria for RECIST 1.1.; means, lytic bone lesions or mixed lytic-blastic bone lesions with identifiable soft tissue components.)
- No prior therapy for locally recurrent or metastatic disease with TKI's (RAS/Raf, MEK, AKT), mTOR inhibitors and angiogenesis inhibitors (VEGV/VEGFR, PDGF/PDGFR) but bevacizumab will be allowed.
- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin ≥ 9.0 g/dl
- Absolute neutrophil count (ANC) ≥ 1,500/mm3
- Platelet count ≥ 100,000/μl
- Total bilirubin ≤ 1.5 x upper limit of normal
- ALT and AST ≤ 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
- Alkaline phosphatase ≤ 4 x upper limit of normal
- PT-INR and PTT ≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
- Serum creatinine ≤ 1.5 x upper limit of normal.
- Signed and dated informed consent before the start of specific protocol procedures.
Who cannot join
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
- Known history of HIV infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 NCI-CTC version 4.02)
- Prior clinical or radiological evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by contrast enhanced head CT scan or MRI
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- History of organ allograft
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- Patients with evidence or history of bleeding diathesis
- Patients undergoing renal dialysis
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours [Ta, Tis \& T1] or any cancer curatively treated > 3 years prior to study entry.
- Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Any condition that is unstable or could jeopardise the safety of the patient and their compliance in the study
- Patients unable to swallow oral medications.
- Patients with intolerance to Paclitaxel.
- Excluded therapies and medications, previous and concomitant:
- Anticancer chemotherapy, hormonotherapy or immunotherapy during the study or within 3 weeks of study entry.
- Radiotherapy within 3 weeks of start of study drug, palliative radiotherapy will be allowed.
- Major surgery within 4 weeks of start of study
- Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Previous treatment with paclitaxel within 1.line and 2.line palliative therapy (Paclitaxel within (neo-) adjuvant therapy is allowed)
Trial locations and contacts
1 site in 1 country.
Germany1 site
Germany Multiple Sites All Over Germany Recruiting Multiple Sites, Germany Contact: iOMEDICO AG
Freiburg im Breisgau, 79108
About this study
Official title: Randomised Phase II Study of Paclitaxel Alone Versus Paclitaxel Plus Sorafenib in Second- or Third-line Treatment of Patients With Metastatic Breast Cancer
AIM OF STUDY
Primary Efficacy Variable:
The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer.
Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death.
Secondary Efficacy Variables:
- Clinical benefit (CR+PR+SD)
- ORR (CR+PR)
- Time to progression
- Time to next Treatment (TTT)
- Overall survival
- Safety profile
Read the detailed description
Today breast carcinoma is the leading cancer type and the second frequent cause of cancer death in adult women. This tumor remains a challenge in modern oncology despite recent advances by introducing new classes of chemotherapy like taxanes and antibodies for the HER-2/neu positive tumors. Recently it was shown that the combination of conventional chemotherapy with a monoclonal antibody against VEGF can further increase the response and progression free survival by combination with an antiangiogenic therapy. It is supposed that this effect might result in a prolonged survival.
Sorafenib, a new developed oral inhibitor for tyrosine kinases which are responsible for the signal transduction after binding to the VEGF receptor and the RAS-Raf-MEK-ERK pathway seems efficient in the treatment of a broad range of tumors.
The multi-kinase inhibitor Sorafenib targets the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β, thereby affecting both, the tumour and the vasculature. Preclinical studies as well as phase I trials showed anti-tumour activity in patients with metastatic breast cancer treated with single-agent sorafenib.
This multicentre, phase II, open-label, randomised study is designed to assess the potential prolongation in progression free survival in patients with metastatic breast cancer in combination with standard chemotherapy paclitaxel compared with the paclitaxel monotherapy.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Paclitaxel and Sorafenib, Paclitaxel
- Keywords
- progression free survival, paclitaxel, sorafenib, metastatic breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paclitaxel and SorafenibDrug
Also called sorafenib = nexavar
intravenous solution, 80 mg/sqm, 3 times per cycle, with one cycle = 28 d and application at days 1, 8 and 15
AND
pills (200mg), cycle 1: 400 mg / day cycle 2: 600 mg / day from cycle 3: 800 mg / day
PaclitaxelDrug
intravenous solution, 80 mg/sqm, 3 times per cycle, with one cycle = 28 d and application at days 1, 8 and 15
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: PA | Active comparator | patient is treated with paclitaxel only Receives: Drug: Paclitaxel |
| Arm 2: PASO | Experimental | patient is treated with paclitaxel AND sorafenib Receives: Drug: Paclitaxel and Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer.
Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death.
Measured: app. 3 yrs
Secondary outcomes (1)
Secondary Efficacy Variables
- Clinical benefit (CR+PR+SD)
- ORR (CR+PR)
- Time to progression
- Time to next Treatment (TTT)
- Overall survival
- Safety profile
Measured: app. 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2011 (estimated)
- Study start1 Jul 2010
- Primary completion31 Aug 2014
- Study completion31 Aug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH
- Sponsor type
- University, hospital or other
- Collaborators
- iOMEDICO AG
- Responsible party
- Sponsor
- Investigators
- Friedrich Overkamp, Dr. med., Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01320111
- Sponsor's protocol ID
- GMIHO-008/2008
- Other IDs
- 2009-018025-73, 2009
- Acronym
- PASO
- Status last verified
- Jul 2014
- First submitted
- 17 Mar 2011
- Last updated
- 20 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. doi: 10.1200/JCO.2007.11.6699.
PubMed 18375893Gradishar W, Kaklamani V, Prasad Sahoo T. A double-blind, randomized, placebo-controlled, Phase 2b study evaluating the efficacy and safety of sorafenib (SOR) in combination with Paclitaxel (PAC) as a first-line therapy in patients with locally recurrent or metastatic breast cancer. Presented at : 32nd Annual San Antonio Breast Cancer Symposium. 2009 Dez 10;(Abstract 44).
Decker T, Overkamp F, Rosel S, Nusch A, Gohler T, Indorf M, Sahlmann J, Trarbach T. A randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib in second- and third-line treatment of patients with HER2-negative metastatic breast cancer (PASO). BMC Cancer. 2017 Jul 25;17(1):499. doi: 10.1186/s12885-017-3492-1.
PubMed 28743247
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Phase II Study of Paclitaxel Alone Versus Paclitaxel Plus Sorafenib in Second- or Third-line Treatment of Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT01320111
- Acronym / sponsor ID
- PASO / GMIHO-008/2008
- Conditions
- Metastatic Breast Cancer
- Keywords
- progression free survival, paclitaxel, sorafenib, metastatic breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbHUniversity, hospital or other
- Collaborators
- iOMEDICO AG
- Study start
- 1 Jul 2010 (actual)
- Primary completion
- 31 Aug 2014 (actual)
- Study completion
- 31 Aug 2014 (actual)
- First posted
- 22 Mar 2011 (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.
AIM OF STUDY
Primary Efficacy Variable:
The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer.
Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death.
Secondary Efficacy Variables:
- Clinical benefit (CR+PR+SD)
- ORR (CR+PR)
- Time to progression
- Time to next Treatment (TTT)
- Overall survival
- Safety profile
Detailed description
Today breast carcinoma is the leading cancer type and the second frequent cause of cancer death in adult women. This tumor remains a challenge in modern oncology despite recent advances by introducing new classes of chemotherapy like taxanes and antibodies for the HER-2/neu positive tumors. Recently it was shown that the combination of conventional chemotherapy with a monoclonal antibody against VEGF can further increase the response and progression free survival by combination with an antiangiogenic therapy. It is supposed that this effect might result in a prolonged survival.
Sorafenib, a new developed oral inhibitor for tyrosine kinases which are responsible for the signal transduction after binding to the VEGF receptor and the RAS-Raf-MEK-ERK pathway seems efficient in the treatment of a broad range of tumors.
The multi-kinase inhibitor Sorafenib targets the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β, thereby affecting both, the tumour and the vasculature. Preclinical studies as well as phase I trials showed anti-tumour activity in patients with metastatic breast cancer treated with single-agent sorafenib.
This multicentre, phase II, open-label, randomised study is designed to assess the potential prolongation in progression free survival in patients with metastatic breast cancer in combination with standard chemotherapy paclitaxel compared with the paclitaxel monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: PA | Active comparator | Drug: Paclitaxelpatient is treated with paclitaxel only |
| Arm 2: PASO | Experimental | Drug: Paclitaxel and Sorafenibpatient is treated with paclitaxel AND sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically or cytologically confirmed adenocarcinoma of the breast
- HER-2/neu negative (primary tumour site HER-2/neu negative by ICH/FISH test)
- Second till third-line of chemotherapy
- Female, age ≥ 18 years.
- ECOG Performance Status of 0 or 1 (Karnofsky-Index ≥ 70%)
Key exclusion criteria (22 listed)
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
- Known history of HIV infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 NCI-CTC version 4.02)
- Prior clinical or radiological evidence of CNS metastases including previously treated, resected, or asymptomatic brain lesions or leptomeningeal involvement by contrast enhanced head CT scan or MRI
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
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 |
|---|---|---|
| Paclitaxel and SorafenibAlso: sorafenib = nexavarintravenous solution, 80 mg/sqm, 3 times per cycle, with one cycle = 28 d and application at days 1, 8 and 15 AND pills (200mg), cycle 1: 400 mg / day cycle 2: 600 mg / day from cycle 3: 800 mg / day | Drug | Arm 2: PASO |
| Paclitaxelintravenous solution, 80 mg/sqm, 3 times per cycle, with one cycle = 28 d and application at days 1, 8 and 15 | Drug | Arm 1: PA |
Primary outcome
Progression free survival (PFS)
Time frame: app. 3 yrs
The primary study objective is the proof of efficacy, measured by progression free survival (PFS) in the treatment of metastatic or locally inoperable recurrent breast cancer. Progression-free survival (PFS) is defined as the time from randomisation to disease progression or death.
1 secondary outcome
Secondary Efficacy Variables
Time frame: app. 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2017.
- Background: PubMed 18375893Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9. doi: 10.1200/JCO.2007.11.6699.
- BackgroundGradishar W, Kaklamani V, Prasad Sahoo T. A double-blind, randomized, placebo-controlled, Phase 2b study evaluating the efficacy and safety of sorafenib (SOR) in combination with Paclitaxel (PAC) as a first-line therapy in patients with locally recurrent or metastatic breast cancer. Presented at : 32nd Annual San Antonio Breast Cancer Symposium. 2009 Dez 10;(Abstract 44).
- Derived from this study: PubMed 28743247Decker T, Overkamp F, Rosel S, Nusch A, Gohler T, Indorf M, Sahlmann J, Trarbach T. A randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib in second- and third-line treatment of patients with HER2-negative metastatic breast cancer (PASO). BMC Cancer. 2017 Jul 25;17(1):499. doi: 10.1186/s12885-017-3492-1.
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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.
Friedrich Overkamp, Dr. med. principal investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel and Sorafenib and Paclitaxel in people with Metastatic Breast Cancer, run by Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH at 1 site in Germany.
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 18 inclusion and 22 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 20 Feb 2017. 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 Germany. 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 phase mean?
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?
Progression free survival (PFS) (time frame: app. 3 yrs). 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 NCT01320111, which also lists 3 linked publications.
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 20 Feb 2017.