Metastatic Breast CancerPhase 1NCT00717340
A Phase 1b/2a, Open-Label, Multi-Center Study of Tivozanib (AV-951) in Combination With Paclitaxel in Subjects With Advanced or Metastatic Breast Cancer
A Phase 1 study testing tivozanib (AV-951) + paclitaxel in people with Metastatic Breast Cancer, run by AVEO Pharmaceuticals, Inc. at 3 sites in 2 countries.
Trial summary
This is a standard Phase 1b and 2a, multi-center, study design that will examine the safety, tolerability, maximum tolerated dose, and overall response rate of tivozanib (AV-951) and paclitaxel in a 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?
- tivozanib (AV-951) + paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Feb 2009to Feb 2011
- Phase
- Phase 1
- 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
- ≥ 18-year-old females
- Histologically or cytologically documented invasive breast cancer
- Documented progressive disease (Phase 1b study) OR documented metastatic disease (Phase 2a study)
- Prior Treatment:
- Phase 1b study: No more than 4 prior chemotherapy treatments, only 1 prior taxane-based regimen for metastatic disease. There is no limit to the number of prior hormonal or biological treatments.
- Phaes 2a study: No prior chemotherapy or biological therapy for metastatic breast cancer. There is no limit to the number of prior hormonal treatments.
Show all 19Show fewer
- Prior adjuvant chemotherapy or biological therapy will not be counted in the number of prior treatments, unless recurrence occurs within 12 months of last dose of adjuvant therapy, in which case it will be counted as 1 prior therapy; adjuvant treatment with a taxane is allowed.
- Measurable or evaluable disease by RECIST criteria (Phase 1b study) (see Appendix A). Subjects to be enrolled in the Phase 2a study are required to have measureable disease according to RECIST.
- No prior VEGF-TKI drugs such as sunitinib, sorafenib, AZ2171, AG013736, GW786034, ZD6474 AMG706, PTK/ZK and other similar agents.
- No treatment with bevacizumab within 4 weeks prior to start of protocol therapy, no prior treatment with other VEGF binding antibodies or VEGF-trap.
- No treatment with the following agents within 3 weeks prior to start of protocol therapy:
- Chemotherapy (at least 6 weeks for nitrosoureas, mitomycin C, and liposomal doxorubicin)
- Other signal transduction inhibitors and monoclonal antibodies
- Immunotherapy or biological response modifiers
- Any experimental therapy
- No treatment with radiotherapy within 2 weeks (if involving < 25% of bone marrow), or 4 weeks (if involving ≥ 25% of bone marrow) prior to start of protocol therapy.
- Resolution of all toxicities
- ECOG performance status ≤ 2 and life expectancy ≥ 3 months.
- Signed and dated written informed consent
Who cannot join
- Known hypersensitivity to paclitaxel or to any other component of the paclitaxel formulation
- Pregnant or lactating women; all fertile subjects must use effective contraception (barrier method) while on study and for 3 months thereafter. All subjects must agree to use a highly effective method of contraception (including their partner). Effective birth control includes (a) IUD plus 1 barrier method, or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm.) Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study.
- Subjects with symptomatic CNS metastases. Subjects with treated brain metastases that have remained stable for at least 3 months without steroids are allowed. Subjects with signs or symptoms or history of brain metastasis must have a CT or MRI scan of the brain within 1 month prior to the start of protocol therapy. Subjects with spinal cord or nerve root compression who have completed treatment at least 4 weeks before the start of protocol therapy and are stable without steroid treatment for at least one week before start of protocol therapy are allowed. Subjects with leptomeningeal metastases are not allowed.
- Any of the following hematologic abnormalities:
- Hemoglobin < 9.0 g/dL
- ANC < 1500 per mm3
Show all 38Show fewer
- Platelet count < 100,000 per mm3
- Any of the following serum chemistry abnormalities:
- Total bilirubin > 1.5 × ULN (>2.5 mg/dL in patients with Gilbert's syndrome)
- AST or ALT > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)
- GGT > 2.5 x ULN (or > 5 × ULN for subjects with liver metastasis)
- Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone metastasis)
- Serum albumin < 3.0 g/dL
- Serum creatinine > 1.5 × ULN
- Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick
- Any other ≥ Grade 3 laboratory abnormality at baseline (other than those listed above)
- Significant cardiovascular disease, including:
- Clinically symptomatic heart failure. Subjects with a history of heart failure must have an ECHO or MUGA scan to document left ventricular ejection fraction (LVEF) > 45% prior to start of protocol therapy
- Uncontrolled hypertension: Blood pressure >140/90 mm Hg on more than 2 antihypertensive medications, on two consecutive measurements obtained at least 24 hours apart. Subjects with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 2 weeks prior to start of protocol therapy.
- Myocardial infarction within 3 months prior to start of protocol therapy
- Baseline neuropathy > Grade 1
- Subjects with delayed healing of wounds, ulcers, and/or bone fractures
- Serious/active infection or infection requiring parenteral antibiotics
- Inadequate recovery from any prior surgical procedure; major surgical procedure within 6 weeks prior to start of protocol therapy.
- Inability to comply with protocol requirements
- Ongoing hemoptysis or history of clinically significant bleeding within 6 months prior to start of protocol therapy
- Cerebrovascular accident within 12 months to start of protocol therapy, or peripheral vascular disease with claudication on walking less than 1 block.
- Deep venous thrombosis or pulmonary embolus within 6 months prior to start of protocol therapy
- Subjects with a "currently active" second primary malignancy other than non-melanoma skin cancers. Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and have been disease free for > 2 years.
- Known concomitant genetic or acquired immune suppression disease such as HIV
- Treatment with systemic hormonal therapy within 3 weeks prior to start of or during protocol therapy, with the exception of:
- Hormonal therapy for appetite stimulation or contraception
- Nasal, ophthalmic, inhaled and topical steroid preparations
- Oral replacement therapy for adrenal insufficiency
- Low-dose maintenance steroid therapy (equivalent of prednisone 10mg/day) for other conditions
- Hormone replacement therapy
- Herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) or CYP3A4 inhibitors within 2 weeks prior to start of or during protocol therapy.
- Full dose oral anticoagulation with warfarin, acenocoumarol, fenprocoumon, or similar agents. If previously receiving these type of agents, a minimum washout of 1 week and documented INR < 1.5 x ULN will be required prior to start of protocol therapy. Full dose anti-coagulation with low molecular weight heparin or unfractionated heparin administered subcutaneously is allowed.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Dana Farber Cancer Institute, Inc.
Boston, Massachusetts, 02115
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
This is a standard Phase 1b and 2a, multi-center, study design that will examine the safety, tolerability, maximum tolerated dose, and overall response rate of tivozanib (AV-951) and paclitaxel in a breast cancer.
Read the detailed description
This is a standard Phase 1b and 2a, multi-center, study design that will examine the safety, tolerability, maximum tolerated dose, and overall response rate of tivozanib (AV-951) and paclitaxel in a breast cancer.
In the Phase 1b study, only the doses of tivozanib (AV-951) will be escalated from 0.5 mg/day to 1.5 mg /day. All subjects will receive doses of weekly paclitaxel chemotherapy.
The Phase 2a study portion of the study was not conducted.
- Conditions
- Metastatic Breast Cancer
- Being tested
- tivozanib (AV-951) + paclitaxel
- Keywords
- tivozanib, AV-951
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tivozanib (AV-951) + paclitaxelDrug
Tivozanib (AV-951):
Subjects in the Phase 1b study will receive 1 dose of tivozanib (AV-951) on Day -5 (± 2 days) for PK sampling prior to Cycle 1 only.
Thereafter in the Phase 1b and 2a study, subjects will receive tivozanib (AV-951) once daily for 3 weeks beginning on Day 1, followed by 1 week off treatment (1 cycle = 4 weeks). On days when paclitaxel and tivozanib (AV-951) are co-administered, AV-951 will be administered immediately following the end of the paclitaxel infusion.
Paclitaxel: Phase 1b study and Phase 2a study:
All subjects will receive IV paclitaxel 90 mg/m2, administered over 1 hour once a week for 3 weeks, followed by 1 week off (1 cycle = 4 weeks).
| Study group | Role | What they receive |
|---|---|---|
| tivozanib (AV-951) + paclitaxel | Experimental | Not described Receives: Drug: tivozanib (AV-951) + paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, tolerability, and maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 1b study)
Measured: 4 weeks (1 Cycle)
To determine the overall response rate of tivozanib (AV-951) in combination with paclitaxel as a first-line chemotherapy for metastatic breast cancer (Phase 2a study)
Measured: 8 weeks (2 Cycles)
Secondary outcomes (6)
To characterize the pharmacokinetic (PK) profile of tivozanib (AV-951) and paclitaxel when administered in combination (Phase 1b study)
Measured: 8 weeks (2 cycles)
To evaluate the antineoplastic activity of tivozanib (AV-951) and paclitaxel when administered in combination (Phase 1b study)
Measured: 8 weeks (2 Cycles)
To perform an exploratory study in a subset of subjects to evaluate (Phase 1b study): -Changes in FMD during treatment with tivozanib (AV-951) -The relationship between hypertension during tivozanib (AV-951) therapy, FMD and plasma NT levels
Measured: 12 weeks (3 Cycles)
To determine the duration of complete and partial responses and time to disease progression (Phase 2a study)
Measured: Not applicable to determine weeks
To determine the safety and tolerability of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 2a study)
Measured: 4 weeks (1 cycle)
To evaluate the effect of tivozanib (AV-951) and paclitaxel on global and targeted gene expression patterns (Phase 2a study)
Measured: 8 weeks (2 Cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2008 (estimated)
- Study startFeb 2009
- Primary completionJan 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVEO Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joshua Zhang, M.D., Study director, AVEO Pharmaceuticals, Inc.Erica Mayer, M.D., Principal investigator, Dana Farber Cancer Institute, Inc.Max E. Scheulen, M.D., Principal investigator, Universitaetsklinikum Essen, GermanyMaura Dickler, M.D., Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00717340
- Sponsor's protocol ID
- AV-951-08-104
- Status last verified
- Jun 2012
- First submitted
- 16 Jul 2008
- Last updated
- 28 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a, Open-Label, Multi-Center Study of Tivozanib (AV-951) in Combination With Paclitaxel in Subjects With Advanced or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00717340
- Acronym / sponsor ID
- AV-951-08-104
- Conditions
- Metastatic Breast Cancer
- Keywords
- tivozanib, AV-951
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- AVEO Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 17 Jul 2008 (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.
This is a standard Phase 1b and 2a, multi-center, study design that will examine the safety, tolerability, maximum tolerated dose, and overall response rate of tivozanib (AV-951) and paclitaxel in a breast cancer.
Detailed description
This is a standard Phase 1b and 2a, multi-center, study design that will examine the safety, tolerability, maximum tolerated dose, and overall response rate of tivozanib (AV-951) and paclitaxel in a breast cancer.
In the Phase 1b study, only the doses of tivozanib (AV-951) will be escalated from 0.5 mg/day to 1.5 mg /day. All subjects will receive doses of weekly paclitaxel chemotherapy.
The Phase 2a study portion of the study was not conducted.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tivozanib (AV-951) + paclitaxel | Experimental | Drug: tivozanib (AV-951) + paclitaxel |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- ≥ 18-year-old females
- Histologically or cytologically documented invasive breast cancer
- Documented progressive disease (Phase 1b study) OR documented metastatic disease (Phase 2a study)
- Prior Treatment:
- Measurable or evaluable disease by RECIST criteria (Phase 1b study) (see Appendix A). Subjects to be enrolled in the Phase 2a study are required to have measureable disease according to RECIST.
Key exclusion criteria (38 listed)
- Known hypersensitivity to paclitaxel or to any other component of the paclitaxel formulation
- Pregnant or lactating women; all fertile subjects must use effective contraception (barrier method) while on study and for 3 months thereafter. All subjects must agree to use a highly effective method of contraception (including their partner). Effective birth control includes (a) IUD plus 1 barrier method, or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm.) Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study.
- Subjects with symptomatic CNS metastases. Subjects with treated brain metastases that have remained stable for at least 3 months without steroids are allowed. Subjects with signs or symptoms or history of brain metastasis must have a CT or MRI scan of the brain within 1 month prior to the start of protocol therapy. Subjects with spinal cord or nerve root compression who have completed treatment at least 4 weeks before the start of protocol therapy and are stable without steroid treatment for at least one week before start of protocol therapy are allowed. Subjects with leptomeningeal metastases are not allowed.
- Any of the following hematologic abnormalities:
- Any of the following serum chemistry abnormalities:
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 |
|---|---|---|
| tivozanib (AV-951) + paclitaxelTivozanib (AV-951): Subjects in the Phase 1b study will receive 1 dose of tivozanib (AV-951) on Day -5 (± 2 days) for PK sampling prior to Cycle 1 only. Thereafter in the Phase 1b and 2a study, subjects will receive tivozanib (AV-951) once daily for 3 weeks beginning on Day 1, followed by 1 week off treatment (1 cycle = 4 weeks). On days when paclitaxel and tivozanib (AV-951) are co-administered, AV-951 will be administered immediately following the end of the paclitaxel infusion. Paclitaxel: Phase 1b study and Phase 2a study: All subjects will receive IV paclitaxel 90 mg/m2, administered over 1 hour once a week for 3 weeks, followed by 1 week off (1 cycle = 4 weeks). | Drug | tivozanib (AV-951) + paclitaxel |
Primary outcome
To determine the safety, tolerability, and maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 1b study)
Time frame: 4 weeks (1 Cycle)
To determine the overall response rate of tivozanib (AV-951) in combination with paclitaxel as a first-line chemotherapy for metastatic breast cancer (Phase 2a study)
Time frame: 8 weeks (2 Cycles)
6 secondary outcomes
To characterize the pharmacokinetic (PK) profile of tivozanib (AV-951) and paclitaxel when administered in combination (Phase 1b study)
Time frame: 8 weeks (2 cycles)
To evaluate the antineoplastic activity of tivozanib (AV-951) and paclitaxel when administered in combination (Phase 1b study)
Time frame: 8 weeks (2 Cycles)
To perform an exploratory study in a subset of subjects to evaluate (Phase 1b study): -Changes in FMD during treatment with tivozanib (AV-951) -The relationship between hypertension during tivozanib (AV-951) therapy, FMD and plasma NT levels
Time frame: 12 weeks (3 Cycles)
To determine the duration of complete and partial responses and time to disease progression (Phase 2a study)
Time frame: Not applicable to determine weeks
To determine the safety and tolerability of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 2a study)
Time frame: 4 weeks (1 cycle)
To evaluate the effect of tivozanib (AV-951) and paclitaxel on global and targeted gene expression patterns (Phase 2a study)
Time frame: 8 weeks (2 Cycles)
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 28 Jun 2012.
Related trials for Metastatic Breast Cancer
RecruitingPhase 3
S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
Cardiotoxicity, HER2/Neu Positive
RecruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8
RecruitingPhase 1
A Study of MGC026 in Participants With Advanced Solid Tumors
Advanced Solid Tumor, Advanced Cancer
RecruitingPhase 1/2
Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma
Not yet recruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08165784 in People With PIK3CA-Mutated Advanced or Metastatic Solid Tumors
Advanced Breast Cancer, Advanced or Metastatic Breast 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.
Joshua Zhang, M.D. study director
AVEO Pharmaceuticals, Inc.
Erica Mayer, M.D. principal investigator
Dana Farber Cancer Institute, Inc.
Max E. Scheulen, M.D. principal investigator
Universitaetsklinikum Essen, Germany
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing tivozanib (AV-951) + paclitaxel in people with Metastatic Breast Cancer, run by AVEO Pharmaceuticals, Inc. at 3 sites in 2 countries.
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 19 inclusion and 38 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 28 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, 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 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.
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?
To determine the safety, tolerability, and maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 1b study) (time frame: 4 weeks (1 Cycle)). 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?
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 28 Jun 2012; AzTrials last refreshed its copy on 29 Oct 2026.