Know Cancer

forgot password

An EORTC-IDBBC/ECSG Phase II Study Evaluating The Role Of The Multi-Drug Resistance (MDR) Reversor, R101933, In Patients With Taxane Refractory Metastatic Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

An EORTC-IDBBC/ECSG Phase II Study Evaluating The Role Of The Multi-Drug Resistance (MDR) Reversor, R101933, In Patients With Taxane Refractory Metastatic Breast Cancer


- Determine the activity of R101933 in combination with paclitaxel or docetaxel in terms
of response to treatment and level of clinical benefit in patients with
taxane-refractory metastatic breast cancer.

- Determine the safety of this regimen in these patients.

- Determine the acute side effects in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive R101933 IV over 1 hour immediately followed by paclitaxel IV over 3 hours
or docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 7 courses in the
absence of disease progression or unacceptable toxicity. Patients who have no disease
progression after 7 courses may continue with treatment at the investigator's discretion.

Patients are followed every 6 weeks until disease progression.

PROJECTED ACCRUAL: A total of 12-35 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed metastatic breast cancer

- Received at least 2 prior courses of paclitaxel-based chemotherapy at doses between
175-200 mg/m^2 (given over 3 hours every 3 weeks) or docetaxel-based chemotherapy at
doses between 75-100 mg/m^2 (given over 1 hour every 3 weeks) as most recent
anticancer therapy

- Evidence of disease resistance

- Progressive disease as best response OR

- Transient response or disease stabilization followed by progression during
taxane-based treatment

- Disease progression on a combination of a taxane and another cytotoxic agent

- Unidimensionally measurable disease

- At least 1 target lesion that clearly progressed or developed during prior
taxane therapy

- Lesions stable or responsive to prior taxane therapy are not considered target

- Lesions that have been irradiated within the past 3 months are not considered
target lesions unless they have clearly progressed or appeared since

- No bone metastases as only site of measurable disease

- No rapidly progressive visceral metastases

- No symptomatic CNS metastases

- Hormone receptor status:

- Not specified



- 18 and over


- Not specified

Menopausal status:

- Not specified

Performance status:

- WHO 0-2

Life expectancy:

- Not specified


- Neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3


- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- Transaminases no greater than 2.5 times ULN (5 times ULN if liver metastases present)


- Creatinine no greater than 1.5 times ULN

- Calcium normal


- LVEF normal by echocardiogram (ECG) or MUGA scan

- QTc less than 450 sec on baseline ECG

- No prior clinically significant arrhythmias requiring treatment

- No cardiac infarction

- No atrial ventricular enlargement or hypertrophy


- No prior toxicity to paclitaxel that would preclude study dose and schedule

- Sodium, potassium, chloride, and bicarbonate normal

- No pre-existing neuropathy greater than grade 2

- No other prior or concurrent malignancy except adequately treated carcinoma in situ
of the cervix, contralateral breast cancer, or nonmelanoma skin cancer or cancer that
has been in remission for more than 5 years

- Not pregnant or nursing

- Fertile patients must use effective contraception


Biologic therapy:

- No concurrent anticancer biologic agents


- See Disease Characteristics

- No more than 8 weeks since last course of prior taxane-based chemotherapy

- No more than 2 prior chemotherapy regimens for metastatic breast cancer

- No other concurrent anticancer chemotherapy

Endocrine therapy:

- No concurrent anticancer hormonal therapy


- See Disease Characteristics

- No concurrent radiotherapy


- Not specified


- No prior multi-drug resistance inhibitor

- No new anticancer therapy initiation since last course of prior taxane-based

- No concurrent angiotensin converting enzyme inhibitor and/or drugs that may prolong
the QTc interval

- No other concurrent anticancer therapy

- Concurrent bisphosphonates for treatment and prevention of bony metastases allowed
provided drugs were initiated prior to study (treatment of hypercalcemia due to
malignancy allowed regardless of time of initiation)

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Bernardo L. Rapoport, MD, MMed(IntMed)

Investigator Role:

Study Chair

Investigator Affiliation:

Medical Oncology Centre of Rosebank


United States: Federal Government

Study ID:




Start Date:

September 2001

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • Breast Neoplasms