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

NCT00717340 | Completed Phase 1

• 1 other identifier: AV-951-08-104
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Metastatic Breast Cancer

Keywords

tivozanib; AV-951

Outcome Measures

Primary Outcomes (2)

• To determine the safety, tolerability, and maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 1b study)

  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)

  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)

  8 weeks (2 cycles)

• To evaluate the antineoplastic activity of tivozanib (AV-951) and paclitaxel when administered in combination (Phase 1b study)

  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

  12 weeks (3 Cycles)

• To determine the duration of complete and partial responses and time to disease progression (Phase 2a study)

  Not applicable to determine weeks

• To determine the safety and tolerability of tivozanib (AV-951) when administered in combination with paclitaxel (Phase 2a study)

  4 weeks (1 cycle)

Study Arms (1)

tivozanib (AV-951) + paclitaxel

EXPERIMENTAL

Drug: tivozanib (AV-951) + paclitaxel

Interventions

tivozanib (AV-951) + paclitaxel DRUG

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).

tivozanib (AV-951) + paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (3)

Dana Farber Cancer Institute, Inc.

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Universitaetsklinikum Essen

Essen, D-45147, Germany

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tivozanib; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Joshua Zhang, M.D.

  AVEO Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Erica Mayer, M.D.

  Dana Farber Cancer Institute, Inc.

  PRINCIPAL INVESTIGATOR

• Max E. Scheulen, M.D.

  Universitaetsklinikum Essen, Germany

  PRINCIPAL INVESTIGATOR

• Maura Dickler, M.D.

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 17, 2008
• Study Start: February 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: February 1, 2011
• Last Updated: June 28, 2012

Record last verified: 2012-06

Locations

DE (1); US (2)