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

NCT01095302 | Completed Phase 1

• 2 other identifiers: TCD11089U1111-1116-5905
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Neoplasms, Malignant

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  3 weeks (cycle 1)

Secondary Outcomes (3)

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

  on-treatment period + 30 days

• Pharmacokinetic profiles of all study drugs and AVE8062 active metabolite based on PK parameters (Cmax, AUC, t1/2, CL, Vss).

  Cycle 1: Day 1 and 3; up to Cycle 4: Day 1

• Objective tumor response as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

  on-treatment period + 30 days

Study Arms (1)

Ombrabulin/ docetaxel/cisplatin

EXPERIMENTAL

AVE8062 combined with docetaxel and cisplatin will be administered once in every 3 weeks, with 30-minute intravenous infusion

Drug: OMBRABULIN (AVE8062); Drug: cisplatin; Drug: docetaxel

Interventions

OMBRABULIN (AVE8062) DRUG

Pharmaceutical form:injection solution Route of administration: intravenous infusion

Ombrabulin/ docetaxel/cisplatin

cisplatin DRUG

Pharmaceutical form:injection solution Route of administration: intravenous infusion

Ombrabulin/ docetaxel/cisplatin

docetaxel DRUG

Pharmaceutical form:injection solution Route of administration: intravenous infusion

Ombrabulin/ docetaxel/cisplatin

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (3)

Investigational Site Number 392003

Akashi-Shi, Japan

Location

Investigational Site Number 392001

Kōtoku, Japan

Location

Investigational Site Number 392002

Nagoya, Japan

Location

Related Publications (1)

• Nishio M, Satouchi M, Horiike A, Horio Y, Sunaga Y, Ecstein-Fraisse E, Hida T. Phase 1 study of ombrabulin in combination with docetaxel and cisplatin in Japanese patients with advanced solid tumors. Jpn J Clin Oncol. 2018 Apr 1;48(4):322-328. doi: 10.1093/jjco/hyy026.

  PMID: 29514256 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

AC 7700; Cisplatin; Docetaxel

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 23, 2010
• First Posted: March 30, 2010
• Study Start: May 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 16, 2013

Record last verified: 2013-10

Locations

JP (3)