Dose Escalation, Safety and Pharmacokinetic Study of AVE8062 in Patients With Solid Tumors

NCT00968916 | Completed Phase 1

• 1 other identifier: TED10967
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Primary objective: To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of AVE8062 administered every 3 weeks in patients with advanced solid tumors. Secondary objectives:

• To assess the overall safety profile of the drug.
• To characterize the pharmacokinetic profile of AVE8062 and its active metabolite RPR 258063.
• To evaluate anti-tumor activity of the drug.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity at Cycle 1

  21 days

Secondary Outcomes (4)

• Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities

  all cycles

• Pharmacokinetic parameters of AVE8062: Cmax, AUC, CL, Vss, and t1/2

  Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles

• Pharmacokinetic parameters of AVE8062's active metabolite RPR258063: Cmax, AUC, t1/2, and Metabolic ratio

  Day 1 and 2 of Cycle 1, and day 1 of subsequent cycles

• Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors in evaluable patients

  from patient informed consent to end of treatment

Study Arms (1)

1

EXPERIMENTAL

Level 1: 15.5 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 2: 25 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 3: 35 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal Level 4: 50 mg/m2 of AVE8062 will be administered once in every 3 weeks, with 30-minute intravenous infusion and continued until unacceptable toxicity or disease progression or patient refusal

Drug: ombrabulin (AVE8062)

Interventions

ombrabulin (AVE8062) DRUG

Pharmaceutical form: injection solution Route of administration: intravenous infusion

1

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Advanced solid tumor that has become refractory to conventional treatment or for which no standard therapy exists.
• Patients with signed and dated Institutional Review Board (IRB)-approved patient informed consent form (ICF) prior to enrollment in the study.

You may not qualify if:

• Eastern Cooperative Oncology Group performance status \> or = 2.
• Life expectancy of less than 12 weeks.
• Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study.
• Absence of histologically or cytologically proven cancer.
• Male patients who do not agree with contraception. Absence of negative serum/urinary pregnancy test within the 7 days prior to the enrollment in the study for female patients with childbearing potential. Patients must be post-menopausal, surgically sterile, or using "effective contraception" (the definition of "effective contraception" will be based on the judgment of the investigator).
• Washout period of less than 28 days from prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy) or any investigational treatment, except for nitrosoureas, mitomycin which may not be used up to 42 days prior to the first cycle. No washout period is required for hormonal therapy, however, it must be discontinued before the first cycle.
• Not recovered from all previous therapies (radiation, surgery, and medications). Adverse events related to previous therapies must be National Cancer Institute Common Terminology Criteria grade \< or = 1 (or alopecia \< or = grade 2) at screening or returned to the subject's baseline prior to their most recent previous therapy.
• Symptomatic brain metastases and carcinomatous leptomeningitis.
• Other serious illness or medical conditions:
• Existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
• Active infection.
• Other serious illness not controlled by adequate treatment.
• Inadequate organ function including:
• Absolute neutrophils counts\<1.5 x 10\^9/L
• Platelets counts\<100 x 10\^9/L

Sponsors & Collaborators

• Sanofi: lead

Study Sites (2)

Sanofi-Aventis Investigational Site Number 392002

Osaka Sayama-Shi, Japan

Location

Sanofi-Aventis Investigational Site Number 392001

Sunto-Gun, Japan

Location

Related Publications (1)

• Murakami H, Kurata T, Onozawa Y, Watanabe J, Ono A, Takahashi T, Yamamoto N, Fujisaka Y, Kiyota H, Hayashi H, Tanaka K, Nakagawa K, Kuroda S. An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):623-30. doi: 10.1007/s00280-014-2388-x. Epub 2014 Jan 30.

  PMID: 24477603 DERIVED

MeSH Terms

Interventions

AC 7700

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

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: August 28, 2009
• First Posted: August 31, 2009
• Study Start: September 1, 2009
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: September 19, 2014

Record last verified: 2014-09

Locations

JP (2)