Clinical trial NCT00248703: Secondary Adjuvant Treatment for Patients With Isolated Tumor Cells in Bone Marrow
Official title: Secondary Adjuvant (Rescue) Treatment With Docetaxel (Taxotere) and Detection of Isolated Tumor Cells in Bone Marrow as a Surrogate Marker for Effect in Node Positive and High Risk Node Negative Breast Cancer After Standard Adjuvant Epirubicin-containing Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Disseminating tumor cells,breast cancer,docetaxel,adjuvant
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: University of Tromso
name: Helse Stavanger HF
name: Sorlandet Hospital HF
name: Sykehuset Innlandet HF
name: Ullevaal University Hospital
name: Sykehuset i Vestfold HF
name: Sykehuset Ostfold
name: Alesund Hospital
First posted: 2005-11-04
Enrollment: 1128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to identify patients with persisting tumor cells after standard epirubicin-containing treatment to test a non-cross resistant chemotherapy regimen (docetaxel) for these patients, and to explore the analysis of disseminated tumor cells in bone marrow as a surrogate marker for clinical outcome.

Detailed description: The presence of disseminating (or isolated) tumor cells (DTC/ITC) in bone marrow (BM) after completion of adjuvant chemotherapy for breast cancer is associated with poor prognosis. Methods for detection of DTC have potential as a tool for monitoring occult residual disease during follow up. Also, there exists potent chemotherapy proven to be effective when anthracycline-based chemotherapy fails (f.ex. docetaxel). Consequently, a study has been started to test DTC detection as a surrogate marker for clinical outcome in localized breast cancer patients, selected by the presence of DTC in BM after standard adjuvant chemotherapy, receiving secondary treatment with docetaxel. In brief, patients having received anthracycline-containing chemotherapy for localized breast cancer are candidates. After informed consent and no radiologic signs of distant metastasis, the first BM aspiration is performed at the end of radiotherapy or 8-12 weeks after the last chemotherapy cycle. The next BM aspiration is performed 6 months later. At that time point the BMs are analyzed for the presence of DTC. If DTC are present in the 6 months BM test (the first BM sample is for exploratory research purposes), 6 cycles of docetaxel are administered (3qw), followed by a third and forth BM analysis 1 month and 13 months after the end of chemotherapy. The patients receiving docetaxel with eradication of the DTC will be clinically compared to those with persistence of DTC after docetaxel treatment.

Eligibility criteria: Inclusion Criteria:

1. Breast cancer with node positive disease or high risk node negative disease (pT1c/T2GII-IIIN0, pT3N0, cT3N0). Patients \< 35 years with pT1a-bN0G2-3.
2. Primary surgery for breast cancer completed
3. Completed 6 cycles of adjuvant (or neoadjuvant) chemotherapy containing anthracycline
4. Age ≥ 18 and \< 70 years
5. Eastern Cooperative Oncology Group or WHO performance status \< 2
6. Written informed consent prior to beginning protocol specific procedures
7. Laboratory requirements (within 5 weeks prior to end of radiation treatment or within 5 weeks prior to completion of baseline examinations):

   Neutrophils ≥ 1.1 10\^9/l, Platelets ≥ 100 10\^9/l, Hemoglobin ≥ 10 g/dl, ASAT and ALAT ≤ x 2.5 UNL (If ALP \> 2.5 ≤ x 5 UNL, then ASAT and ALAT ≤ x 1.5 UNL), ALP ≤ x 5 UNL (If ASAT and ALAT \> 1.5 ≤ x 2.5 UNL, then ALP ≤ 2.5 x UNL), Creatinine ≤ 175 umol/l
8. Completed staging analysis including chest X-ray, bone scintigraphy or MRI, liver ultrasound or liver CT scan

Exclusion Criteria:

1. Other (than breast carcinoma) earlier or concomitant carcinoma, except for skin and in situ cervix cancer
2. M1 breast cancer or locoregional recurrence of previously diagnosed breast cancer.
3. Earlier treatment with paclitaxel or docetaxel.
4. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria (see appendix II)
5. Cardiac disease with symptoms classified as NYHA ≥ 2
6. Definite contraindications for the use of corticosteroids
7. Concurrent treatment with other experimental drugs
8. Concurrent treatment with any other anti-cancer therapy (except for endocrine therapy and trastuzumab)
9. Pregnancy

Primary outcomes:
measure: Disease free survival related to presence or absence of disseminated tumor cells
timeFrame: At approximately 8 years maximum FU
Secondary outcomes:
measure: Predictive value of primary tumor markers on effects of docetaxel
timeFrame: At approximately 8 years maximum FU
measure: Explore markers on tumor cells in bone marrow that can predict the effect of docetaxel
timeFrame: At approximately of 8 years maximum FU
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: RRHF
Study officials:
affiliation: Oslo University Hospital
name: Bjørn Naume, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Naume B, Synnestvedt M, Falk RS, Wiedswang G, Weyde K, Risberg T, Kersten C, Mjaaland I, Vindi L, Sommer HH, Saetersdal AB, Rypdal MC, Bendigtsen Schirmer C, Wist EA, Borgen E. Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer. J Clin Oncol. 2014 Dec 1;32(34):3848-57. doi: 10.1200/JCO.2014.56.9327. Epub 2014 Nov 3.
citation: Gilje B, Nordgard O, Tjensvoll K, Borgen E, Synnestvedt M, Smaaland R, Naume B. Comparison of molecular and immunocytochemical methods for detection of disseminated tumor cells in bone marrow from early breast cancer patients. BMC Cancer. 2014 Jul 15;14:514. doi: 10.1186/1471-2407-14-514.
citation: Synnestvedt M, Borgen E, Wist E, Wiedswang G, Weyde K, Risberg T, Kersten C, Mjaaland I, Vindi L, Schirmer C, Nesland JM, Naume B. Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study. BMC Cancer. 2012 Dec 22;12:616. doi: 10.1186/1471-2407-12-616.