Pharmacokinetics and Safety Study of Cabazitaxel in Cancer Patients With Renal Impairment

Sanofi

Status and phase: Completed; Phase 1

Conditions: Neoplasm Malignant

Treatments: Drug: Cabazitaxel XRP6258

Study type: Interventional

Funder types: Industry

Identifiers

NCT01527929

U1111-1121-4512 (Other Identifier)

2011-001517-14 (EudraCT Number)

POP12251

Details and patient eligibility

About

Primary Objective:

• To assess potential impact of moderate and severe renal impairment on the pharmacokinetics of cabazitaxel

Secondary Objective:

• To assess the safety of cabazitaxel in patients with various degrees of renal impairment

Full description

The study consists of a screening phase, registration, cabazitaxel administration will start within 5 business days of registration, with 21-day study treatment cycles. Cycle lengths may be extended up to a maximum of 14 additional days in case of unresolved toxicity. Patients continue to receive treatment until they experience, unacceptable toxicities/Adverse Events, disease progression, withdraw their consent, or the investigator decides to discontinue the patient, and the subsequent 30 days follow-up or study cut-off, whichever comes first.

Patients may continue to be treated as long as they are benefiting from study treatment and have not met study withdrawn criteria.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Diagnosis of histologically or cytologically proven non-hematologic malignancy. The cancer must be one that is either refractory to standard therapy or for which no standard therapy exists. Cabazitaxel is an adequate treatment option, as judged by investigator.

• Eastern Cooperative Oncology Group performance status 0 - 2

• Stable renal function

• Patients must have adequate liver and marrow function as defined below:

  • Absolute neutrophil count ≥ 1.5x10^9/L
  • Platelets ≥ 100x10^9/L
  • Total bilirubin ≤ 1.0 x the institutions upper limit of normal
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x the institutions upper limit of normal
  • Alkaline phosphatase ≤ 2.5 x the institutions upper limit of normal

• Patient may have a Grade 1 or less neurotoxicity at study entry.

• Life expectancy > 3 months

• Age ≥ 18 years old

• If female, subject must use a double contraception method, except if she is sterilized for more than 3 months or postmenopausal.

• Having given written informed consent prior to any procedure related to the study

Exclusion criteria:

• Less than 4 weeks have elapsed from prior anticancer therapy (surgery, chemotherapy, radiation therapy, hormonal therapy and immunotherapy). Prior isotope therapy and radiotherapy to ≥ 30% of bone marrow are not allowed.
• Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, class III or IV congestive heart failure, stroke or transient ischemic attack.
• Any of the following within 3 months prior to study start: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.
• Active hepatitis
• Acute renal failure (new or superimposed to pre-existing chronic renal impairment), nephrotic syndrome.
• Patients requiring dialysis during the study.
• History of hypersensitivity to docetaxel or polysorbate 80.
• Known acquired immunodeficiency syndrome (AIDS-related illnesses) or known HIV disease requiring antiretroviral treatment.
• Known brain metastases.
• If female, pregnancy or breast-feeding.
• Any treatment known to induce CYP isoenzymes (e.g., phenobarbital, phenytoin, carbamazepine, rifampicin, St John's Wort) or to strongly inhibit CYP3A4 activities (e.g., ketoconazole, itraconazole, macrolides, antiprotease agents, etc) is not allowed within 2 weeks before or during the test period of the pharmacokinetic sampling

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

Cohort A

Experimental group

Description:

Normal renal function - Cabazitaxel administered once every 3 weeks

Treatment:

Drug: Cabazitaxel XRP6258

Cohort B

Experimental group

Description:

Moderate renal dysfunction - Cabazitaxel administered once every 3 weeks

Treatment:

Drug: Cabazitaxel XRP6258

Cohort C

Experimental group

Description:

Severe renal dysfunction - Cabazitaxel administered once every 3 weeks

Treatment:

Drug: Cabazitaxel XRP6258