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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01095302
First received: March 23, 2010
Last updated: October 12, 2013
Last verified: October 2013
  Purpose

Primary Objective:

  • To determine the maximum tolerated dose based on the incidence of dose limiting toxicity and the maximum administered dose of ombrabulin in combination with docetaxel and cisplatin administered every 3 weeks in patients with advanced solid tumors

Secondary Objectives:

  • To assess the overall safety profile of the combination therapy
  • To characterize the pharmacokinetic profile of ombrabulin, its active metabolite RPR 258063, docetaxel and cisplatin in combination.
  • To evaluate anti-tumor activity of the combination therapy

Condition Intervention Phase
Neoplasms, Malignant
Drug: OMBRABULIN (AVE8062)
Drug: cisplatin
Drug: docetaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Dose-escalation, Safety and Pharmacokinetics Phase I Study of Ombrabulin in Combination With Docetaxel and Cisplatin Every 3 Weeks in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Dose limiting toxicity [ Time Frame: 3 weeks (cycle 1) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Global safety profile based on treatment emergent adverse events, serious adverse events, and laboratory abnormalities [ Time Frame: on-treatment period + 30 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profiles of all study drugs and AVE8062 active metabolite based on PK parameters (Cmax, AUC, t1/2, CL, Vss). [ Time Frame: Cycle 1: Day 1 and 3; up to Cycle 4: Day 1 ] [ Designated as safety issue: No ]
  • Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [ Time Frame: on-treatment period + 30 days ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: May 2010
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ombrabulin/ docetaxel/cisplatin
AVE8062 combined with docetaxel and cisplatin will be administered once in every 3 weeks, with 30-minute intravenous infusion
Drug: OMBRABULIN (AVE8062)

Pharmaceutical form:injection solution

Route of administration: intravenous infusion

Drug: cisplatin

Pharmaceutical form:injection solution

Route of administration: intravenous infusion

Drug: docetaxel

Pharmaceutical form:injection solution

Route of administration: intravenous infusion


Detailed Description:

The duration of the study for each patient will include an up to 4-week screening phase, 21-day study treatment cycles, an end of treatment visit and a follow-up period 30 days after the last infusion of ombrabulin. The patient will continue treatment until disease progression, unacceptable toxicity, patient's refusal of further treatment.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients with advanced solid tumor for which docetaxel and cisplatin is approved such as lung cancer, epithelial ovarian cancer.

Exclusion criteria:

  • Eastern Cooperative Oncology Group performance status > or = 2.
  • Concurrent treatment with any other anticancer therapy.
  • Male or female patients who do not agree with contraception.
  • Washout period of less than 28 days from prior anticancer therapies (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 that has to 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 (NCI-CTCAE V3.0) 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 not controlled by adequate treatment
  • Patients with more than 1 line of previous chemotherapy for advanced or metastatic disease (adjuvant/neoadjuvant and targeted agents [eg gefitinib] excluded).
  • Current peripheral neuropathy > or = grade 2 and ototoxicity, of any origin including significant residual symptoms due to the use of neurotoxic drugs (eg vincaalkaloids, platinum and taxanes).
  • Inadequate organ function
  • Documented medical history of myocardial infarction, documented angina pectoris, arrhythmia especially severe conduction disorder such as second or third degree atrio-ventricular block, stroke, or history of arterial or venous thrombo-embolism within the past 180 days requiring anticoagulants.
  • Patient with a left ventricular ejection fraction <50% by echocardiography.
  • Patients with a baseline QTc interval >0.45, or family history of Long QT Syndrome.
  • Patient with uncontrolled hypertension and patient with organ damage related to hypertension such as left ventricular hypertrophy or grade 2 ocular fundoscopic changes or kidney impairment.
  • Patients with growing vessel disease (eg age-related macular degeneration, diabetic retinopathy, rheumatoid arthritis), or ongoing wound healing process. Patients should be enrolled in the study at least 28 days after surgery.
  • 12-lead Electrocardiogram: ST- and T-wave changes suggesting ischemia
  • Hypertension defined as systolic blood pressure (BP)>140 mmHg or diastolic BP>90 mmHg on two repeated measurements at 30 minutes intervals.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01095302

Locations
Japan
Investigational Site Number 392003
Akashi-Shi, Japan
Investigational Site Number 392001
Koto-Ku, Japan
Investigational Site Number 392002
Nagoya-Shi, Japan
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01095302     History of Changes
Other Study ID Numbers: TCD11089, U1111-1116-5905
Study First Received: March 23, 2010
Last Updated: October 12, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Neoplasms
Docetaxel
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014