A Study of Cabazitaxel for Patients With Breast or Lung Cancer and Recurrent or Progressive Brain Metastases - Cabazitaxel for Brain Metastases (CaBaMet) (CaBaMet)

A Phase II Study of Cabazitaxel for Patients With Breast or Lung Cancer and Recurrent or Progressive Brain Metastases - Cabazitaxel for Brain Metastases (CaBaMet)

Patients suffering from histologically or cytologically confirmed stage IV lung or breast cancer with progressive or recurrent brain metastases after prior external beam radiotherapy will receive treatment with cabazitaxel until progression of brain metastases (BM) or unacceptable toxicity.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Lung Cancer; Recurrent Brain Metastases; Progressive Brain Metastases
• Intervention / Treatment: Drug: Cabazitaxel

Detailed Description

Cabazitaxel is a new taxane compound that exhibited a broad spectrum of in vivo antitumor activity, not only in docetaxel - sensitive tumor models, but also in tumors models in which docetaxel was poorly or not active. In contrast to other taxanes, cabazitaxel has the ability to cross the blood-brain-barrier. Marked antitumor activity was obtained in nude mice bearing intracranial glioblastomas. Consequently, there is a good rationale to investigate cabazitaxel in patients with breast or lung cancer and recurrent or progressive brain metastases.

The primary object of the study is to measure objective tumor response of brain metastases for patients with breast or lung cancer and recurrent or progressive brain metastases.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bayern
    • Weiden, Bayern, Germany, 92637
      • Kliniken Nordoberpfalz, AG Klinikum Weiden, Medizinische Kliniken I

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients (≥ 18 years of age)
2. Histologically or cytologically confirmed stage IV lung or breast cancer with progressive or recurrent brain metastases
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
4. Prior external beam radiotherapy (WBRT or SRS) of BM Patients suffering from small cell lung cancer (SCLC) who have been treated with chemotherapy and prophylactic cranial radiotherapy may be also enrolled.
5. At least one two-dimensional measurable lesion on brain MRI
6. Life expectancy at least 3 months
7. Females of childbearing potential (FCBP) must have a negative pregnancy test within 7 days of the first application of study treatment and must agree to use effective contraceptive birth control measures (Pearl Index < 1) during the course of the Trial. A female subject is considered to be of childbearing potential unless she is age ≥ 50 years and naturally amenorrhoeic for ≥ 2 year, or unless she is surgically sterile.
8. Males must agree to use effective contraception (Pearl Index < 1) during the course of the trial and for at least 6 months after last administration of study medication cabazitaxel. In addition males must agree to prevent contact with the ejaculate by another person throughout study treatment.

Exclusion Criteria:

1. Prior chemotherapy or targeted therapy (e.g. erlotinib, bevacizumab) for brain metastases
2. Any chemotherapy or targeted tumor therapy within two weeks of study inclusion or concomitantly
3. Any antihormonal tumor treatment within two weeks of study inclusion or concomitantly
4. Time interval to prior external beam radiotherapy less than 2 weeks
5. Suspected or known leptomeningeal disease
6. Peripheral neuropathy ≥ grade 2

7. Inadequate organ and bone marrow function as evidenced by:

   • Absolute neutrophil count (ANC) < 1.5 x 10*9/L;
   • Hemoglobin < 10.0 g/dL;
   • Platelet count < 100 x 10*9/L;
   • Total bilirubin ≥ 1 x upper limit of normal (ULN);
   • AST/GOT and/or ALT/GPT ≥ 1.5 x ULN;
   • Serum creatinine > 1.5 x ULN. If creatinine 1.0 - 1.5 x ULN; creatinine clearance has to be calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and patients with creatinine clearance < 60 mL/min must be excluded
8. Other inadequate organ function according to investigator's discretion
9. History of hypersensitivity reaction to docetaxel
10. History of hypersensitivity reaction to polysorbate 80 containing drugs
11. Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
12. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week washout period is necessary for patients who are already on these treatments; see also Section 10 and Appendix 3 and 4; dexamethasone is allowed)
13. Recently received or planned vaccination against yellow fever during study treatment
14. Pregnant or breast feeding females
15. Participation in any other clinical trial or treatment with any experimental drug within 28 day before enrolment to the study or during study participation until the end of treatment visit
16. Previous or concurrent tumor other than underlying tumor disease (breast or lung cancer) with the exception of cervical cancer in situ, adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, superficial bladder tumors (Ta,Tis, and T1) or any curatively treated tumors > 5 years prior to enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Patients receive Cabazitaxel 25 mg/m2 i.v. infusion. This trial is a single arm trial.	Drug: Cabazitaxel; Cabazitaxel 25 mg/m2 i.v. infusion (infusion time about 1h) on D1 of each 21-day cycle. Continuation of treatment until progression of brain metastases or unacceptable toxicity.; Other Names: XRP6258, RPR116258A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective tumor response of brain metastases	Objective tumor response of brain metastases (Complete response (CR) or partial response (PR) or at least a minor response (MR; 25-50% reduction) according to WHO criteria1,2 and Iwamoto3 confirmed by magnetic resonance imaging (MRI))	approx. 12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Efficacy measure	approx. 12 month
Progression free-survival for brain metastases	Efficacy measure	approx. 12 month
progression-free survival for extracerebral tumor disease	Efficacy measure	approx. 12 month
Time to treatment failure of brain metastases	Efficacy measure	12 month
Quality of life	Efficacy measure, assessed with EORTC QLQ-C30 and additional module BN20 questionnaire	approx. 12 month
Type, incidence and severity of adverse events	Safety measure	approx. 12 month
Dose reduction or discontinuation of study drug cabazitaxel due to adverse events	Safety measure	approx. 12 month

Collaborators and Investigators

• Sponsor: AIO-Studien-gGmbH
• Collaborators: Sanofi; ClinAssess GmbH
• Investigators: Principal Investigator: Frank Kullmann, Prof. Dr., Kliniken Nordoberpfalz AG, Klinikum Weiden, Medizinische Kliniken I

Publications and helpful links

Helpful Links

• Working Group for Medical Oncology (AIO) from the German Cancer Society (DKG)

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): January 18, 2018

Study Registration Dates

• First Submitted: June 16, 2014
• First Submitted That Met QC Criteria: June 17, 2014
• First Posted (Estimate): June 18, 2014

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 19, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: metastases; Patients with breast or lung cancer and recurrent or progressive brain
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Disease Attributes; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Recurrence; Brain Neoplasms; Neoplasms, Second Primary
• Other Study ID Numbers: AIO-ZNS-0113; 2013-005545-37 (EudraCT Number); CABAZL06457 (Other Identifier: Sanofi-Aventis)