Dose-Escalation, Safety, Pharmacokinetics Study of Cabazitaxel With Gemcitabine In Patients With Solid Tumor

NCT01001221 | Terminated Phase 1 Results

• 1 other identifier: TCD11068
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 4

Brief Summary

Primary Objectives:

• Study part 1: To determine the Maximum Tolerated Dose (MTD) and the Dose Limiting Toxicities (DLTs) of cabazitaxel administered as a 1-hour infusion in combination with gemcitabine, every 3 weeks in patients with advanced solid malignancies.
• Study part 2: To determine the antitumor activity of cabazitaxel in combination with gemcitabine, in an additional extended cohort of 15 patients with advanced solid malignancies treated with the defined MTD, as assessed by objective response rate (ORR) according to the revised guideline for Response Evaluation Criteria in Solid Tumours (RECIST 1.1 criteria). Secondary Objectives:
• To assess the safety profile of the combination regimen of cabazitaxel with gemcitabine.
• To assess the pharmacokinetics (PK) of cabazitaxel, gemcitabine and its metabolite 2',2' difluorodeoxyuridine (dFdU) when given in combination.
• To determine Time to Progression (TTP), Objective Response Rate (ORR), and Duration of Response (DR), in the extended cohort of patients treated at the MTD in Part 2 of the study and the patients who received the MTD in Part 1 component. For study part 1, dose levels were to be escalated according to predefined dose escalation decision rules. The Maximum Administered Dose (MAD) was reached at the dose level when at least 2 patients developed a DLT during the first 3 weeks of treatment. There was no further dose escalation when this dose was achieved. The MTD was defined as the highest dose at which 0 or 1 of 3 to 6 patients, respectively, experienced DLT during the first 3 weeks of treatment.

Conditions

Neoplasms, Malignant

Outcome Measures

Primary Outcomes (2)

• Participants With Dose Limiting Toxicities During Dose Escalation

  Dose Limiting Toxicities (DLTs) were defined as clinical adverse events (AE) or laboratory abnormalities considered drug-related as assessed by the Investigator or Sponsor, and achieving a Common Terminology Criteria for Adverse Events v3.0 (CTCAE) severity rating of severe (3) or life-threatening (4).

  Day 1 to Day 21 of the first treatment cycle

• Objective Response Rate With MTD

  Objective response was defined as a confirmed complete response (CR) or a confirmed partial response (PR) during the treatment period, based on RECIST 1.1, as assessed by the Investigator. CR: Disappearance of all target lesions, all non-target lesions, and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion. The objective response rate (ORR) was to be calculated as the proportion of participants with confirmed objective response relative to the total number of participants in the analysis population. Due to the inability to determine MTD during the study part 1, the analysis was not performed.

  Fron Day 1 up to a maximum of 12 months

Secondary Outcomes (41)

• Time To Progression With MTD

  Fron Day 1 up to a maximum of 12 months

• Duration of Response With MTD

  Fron Day 1 up to a maximum of 12 months

• Participants With Adverse Events

  from first dose of study medication up to 30 days after the last dose of study medication (maximum follow-up of 68 weeks)

• Pharmacokinetic of Cabazitaxel on Cycle 1: Maximum Plasma Concentration Observed (Cmax)

  before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

• Pharmacokinetic of Cabazitaxel on Cycle 1: Time to Maximum Concentration (Tmax)

  before the start of infusion and 5 minutes before the end of infusion, then 5, 15, 30 minutes, 1, 2, 3, 5, 7, 10, 24, 48, 72, 120 and 168 hours after the end of infusion

Study Arms (1)

Cabazitaxel + gemcitabine

EXPERIMENTAL

Cabazitaxel and gemcitabine on Day 1 then gemcitabine alone on Day 8 every 3 weeks until disease progression or unacceptable toxicities, withdrawal of consent or Investigator's decision. On Day 1, cabazitaxel was given either first followed by gemcitabine (part 1a) or after gemcitabine with 1 hour gap between the two infusions (part 1b). Required premedication with antihistamine, corticosteroid and H2 antagonist was administered intravenously 30 minutes before each dose of cabazitaxel.

Drug: cabazitaxel; Drug: gemcitabine

Interventions

cabazitaxel DRUG

Pharmaceutical form: 60 mg/1.5 ml concentrate solution for infusion Route of administration: Intravenous infusion over 60 minutes Dosage: * Study part 1: 15, 20 or 25 mg/m\^2 according to pre-defined dose escalation schedule * Study part 2: MTD as determined in Study part 1

Also known as: XRP6258, Jevtana

Cabazitaxel + gemcitabine

gemcitabine DRUG

Pharmaceutical form: According to United States Package Insert (USPI) Route of administration: Intravenous infusion over 30 minutes Dosage: * Study part 1: 700, 900 or 1000 mg/m\^2 according to pre-defined dose escalation schedule * Study part 2: MTD as determined in Study part 1.

Also known as: Gemzar

Cabazitaxel + gemcitabine

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed advanced solid malignancy that is metastatic or unresectable, and for which standard curative measures do not exist.

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) \> or =2
• Anticipation of need for a major surgical procedure or radiation therapy during the study treatment
• Absence of completion of all prior chemotherapy, biological therapy, targeted non-cytotoxic therapy \> or = 3 weeks; and radiotherapy \> or = 4 weeks prior to registration. For part 2 only, prior treatment with radiotherapy, chemoembolization therapy, or cryotherapy is allowed if these therapies are not directed to the areas of measurable disease being used for the purposes of this protocol. (4 weeks of washout period is required prior to start the treatment in Part 2)
• Concurrent treatment in another clinical trial or with any other cancer therapy or patients planning to receive these treatments during the study
• Other concurrent serious illness or medical condition, including active infection or human immunodeficiency virus (HIV) disease
• History of any other malignancy with the exception of adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri
• Other severe acute or chronic medical or psychiatric condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient's safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
• Symptomatic brain metastases or leptomeningeal disease. Patients with asymptomatic or stable brain metastases are allowed
• Women of childbearing potential not protected by highly effective contraceptive method of birth control. All patients of childbearing potential that do not have a negative pregnancy test within the 7 days prior to registration
• Patients who are pregnant or breastfeeding
• For part 2, absence of measurable disease as defined by the most current version of the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. For the Part 1 component, patients with non-measurable disease are accepted
• Inadequate bone marrow or liver or renal organ function
• Any condition which is considered a contraindication to gemcitabine in the local labelling
• Prior treatment with cabazitaxel within the last 2 years
• History of severe hypersensitivity grade 3 or 4 to taxanes, Polysorbate-80, or to compounds with similar chemical structures

Sponsors & Collaborators

• Sanofi: lead

Study Sites (4)

Investigational Site Number 840002

Detroit, Michigan, 48201, United States

Location

Investigational Site Number 840005

Cincinnati, Ohio, 45267-0542, United States

Location

Investigational Site Number 840004

Philadelphia, Pennsylvania, 19111, United States

Location

Investigational Site Number 840001

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

cabazitaxel; XRP6258; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Pharmacokinetic results need to be confirmed due to the limited data available.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: sanofi-aventis

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: October 23, 2009
• First Posted: October 26, 2009
• Study Start: November 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: September 11, 2013
• Results First Posted: September 11, 2013

Record last verified: 2013-09

Locations

US (4)