A Phase 1b/2a, Open-Label, Multi-Center Study of AV-951 in Combination with Paclitaxel in Subjects with Advanced or Metastatic Breast Cancer
- Conditions
- Advanced or metastatic breast cancerMedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer
- Registration Number
- EUCTR2008-002109-38-DE
- Lead Sponsor
- AVEO Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- Female
- Target Recruitment
- 84
Subjects must meet all of the following inclusion criteria to be eligible for participation in the study:
1. = 18-year-old females
2. Histologically or cytologically documented invasive breast cancer
3. Documented progressive disease (Phase 1b study) OR documented metastatic disease (Phase 2a study)
4.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.
•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.
5.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.
6.No prior VEGF-TKI drugs such as sunitinib, sorafenib, AZ2171, AG013736, GW786034, ZD6474 AMG706, PTK/ZK and other similar agents.
7.No treatment with bevacizumab within 4 weeks prior to start of protocol therapy, no prior treatment with other VEGF binding antibodies or VEGF-trap.
8. 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
9. 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.
10. Resolution of all toxicities associated with prior treatment to = Grade 1 (except for Grade 2 alopecia) prior to start of protocol therapy.
11. ECOG performance status = 2 and life expectancy = 3 months
12. Signed and dated written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Subjects meeting any of the following criteria are ineligible for participation in the study:
1. Known hypersensitivity to paclitaxel or to any other component of the paclitaxel
formulation.
2. 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.
3. 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.
4. Any of the following hematologic abnormalities:
• Hemoglobin < 9.0 g/dL
• ANC < 1500 per mm3
• Platelet count < 100,000 per mm3
5. 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)
6. Significant cardiovascular disease, including:
• Clinically symptomatic heart failure.
• Uncontrolled hypertension
7. Baseline neuropathy > Grade 1
8. Subjects with delayed healing of wounds, ulcers, and/or bone fractures
9. Serious/active infection or infection requiring parenteral antibiotics
10. Inadequate recovery from any prior surgical procedure; major surgical procedure within 6 weeks prior to start of protocol therapy.
11. Inability to comply with protocol requirements
12. Ongoing hemoptysis or history of clinically significant bleeding within 6 months to start of protocol therapy.
13. Cerebrovascular accident within 12 months to start of protocol therapy, or peripheral vascular disease with claudication on walking less than 1 block.
14. Deep venous thrombosis or pulmonary embolus within 6 months prior to start of protocol therapy.
15. 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.
16. Known concomitant genetic or acquired immune suppression disease such as HIV.
17. Treatment with systemic hormonal therapy within 3 weeks prior to start of or during proto
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method