AzTrials
AzTrials

Breast CancerNCT00795678

Chemotherapeutic Agents in Brain/Breast

An observational study of Breast Cancer and Metastatic Cancer, run by Case Comprehensive Cancer Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer, Metastatic Cancer
What is being tested?
capecitabine, cyclophosphamide and doxorubicin hydrochloride
How many people
10 participants
Where
2 sitesUnited States
Study dates
Sep 2008to Apr 2013
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients will be recruited from a population of breast cancer patients who are to undergo clinically indicated surgical resection of one of more symptomatic brain metastasis(es) treated at the investigational centers.

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed breast carcinoma with ≥ 1 suspected or known parenchymal brain metastases for which surgical resection or biopsy is clinically indicated
  • Treating oncologist must agree that the patient would derive clinical benefit from receiving ≥ 1 of the following study agents:
  • Capecitabine, cyclophosphamide, doxorubicin hydrochloride, gemcitabine hydrochloride, lapatinib ditosylate, paclitaxel, trastuzumab (Herceptin®), or vinorelbine ditartrate
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Menopausal status not specified
  • Karnofsky performance status 50-100%
  • Life expectancy ≥ 3 months
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin (total) ≤ 1.5 times ULN
  • AST ≤ 3 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for three months after completion of study treatment
  • No severe NYHA class III-IV cardiac insufficiency with uncontrolled and/or unstable cardiac or coronary artery disease
  • No history of noncompliance to medical regimens or inability or unwillingness to return for all scheduled visits

PRIOR CONCURRENT THERAPY:

  • No toxicity > grade 2 from prior chemotherapy or radiotherapy remains at the time of study entry
  • At least 60 days since prior bevacizumab
  • At least 4 weeks since prior cranial radiotherapy
  • At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 2 weeks since prior non-cytotoxic drugs (e.g., small molecule-targeted drugs)
  • No concurrent experimental therapies
  • Concurrent hormone therapy and/or trastuzumab (Herceptin®) allowed

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • Memorial Sloan Kettering

    New York, New York, 10065

Other trials in United States

About this study

Official title: Clinical Study to Assess Entry of Chemotherapeutic Agents Into Brain Metastases in Women With Breast Cancer

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Studying samples of tumor tissue and blood from patients may help doctors understand how well these drugs can be carried to the brain.

PURPOSE: More definitive knowledge of the penetration of chemotherapeutic and other agents into the brain is necessary for the future rational design of drug and drug regimens that target brain metastases. This clinical trial is studying how well capecitabine, cyclophosphamide, doxorubicin, gemcitabine, lapatinib, paclitaxel, trastuzumab, or vinorelbine penetrates brain tumors.

Read the detailed description

OBJECTIVES:

  • To determine the concentration of capecitabine, cyclophosphamide, doxorubicin hydrochloride, gemcitabine hydrochloride, lapatinib ditosylate, paclitaxel, trastuzumab (Herceptin®), or vinorelbine ditartrate in brain metastases in women with breast cancer.
  • To analyze drug penetrability by modeling the relationship between drug concentration in the tumor and drug concentration in blood samples.

OUTLINE: Patients are assigned to receive 1 of the 8 agents by the patient's treating oncologist.

Patients receive a single dose of the following study drugs immediately preceding surgery: oral capecitabine; cyclophosphamide IV over 30 minutes; doxorubicin hydrochloride IV over 15 minutes; gemcitabine hydrochloride IV over 30 minutes; oral lapatinib ditosylate*; paclitaxel IV over 3 hours; trastuzumab (Herceptin®) IV over 30-90 minutes; or vinorelbine ditartrate IV over 10-30 minutes . Patients then undergo craniotomy for resection of the brain metastases.

NOTE: *Patients receive oral lapatinib ditosylate at least 3 days prior to surgery and immediately before surgery.

All patients receiving cyclophosphamide, doxorubicin hydrochloride, gemcitabine hydrochloride, paclitaxel, or vinorelbine ditartrate also receive a single dose of pegfilgrastim subcutaneously (SC) 24-48 hours after the study drug administration OR filgrastim (G-CSF) SC once daily for 10 days, beginning 24-48 hours after the study drug administration.

Blood samples are collected periodically for pharmacological studies. Tissue samples obtained at surgical resection and blood samples are used to establish cell lines and analyzed for drug concentration by HPLC, LC-MS/MS or ELISA.

Keywords
tumors metastatic to brain, stage IV breast cancer
Medical subject headings
Breast Neoplasms, Neoplasm Metastasis, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • capecitabineDrug

    Also called Capecitabine (Xeloda®) (NSC-712807)

    Capecitabine is an oral prodrug of 5 deoxy-5-fluorouridine (5DFRU) that is converted to 5-fluorouracil (5-FU). 5-FU is metabolized to 5-fluoro-2-deoxyuridine monophosphate (fDUMP) and 5-fluorouridine triphosphage (FUTP) which cause cell injury. Capecitabine is supplied in 150 mg (light peach colored) and 500 mg tablets (film coated)and will be administered pre-operatively.

  • cyclophosphamideDrug

    Also called Cyclophosphamide (Cytoxan) (NCS-26271)

    Cyclophosphamide is biotransformed principally in the liver to active alkylating metabolites that cross-link tumor cell DNA. Cyclophosphamide is supplied in 100 mg, 200 mg, 500 mg and 1 gram and 2 gram vials as a white powder. The drug should be reconstituted with Sterile Water for Injection, USP, and may be diluted in either normal saline or D5W. Cyclophosphamide will be mixed in 250 mL of D5W and infused over 30 minutes prior to surgery.

  • doxorubicin hydrochlorideDrug

    Also called Doxorubicin (Adriamycin) (NSC-123127)

    Doxorubicin is an anthracycline anticancer agent which mediates tumoricidal effects by intercalating into double-stranded DNA and producing structural changes that disrupt DNA and RNA synthesis. Doxorubicin is supplied in 10, 20, and 50 mg single use vials, and 150 mg multidose vials as a red-orange, lyophilized power which has a storage stability of a least two years. The dose will be given 60mg/m2 over 15 minutes of time pre-operatively.

  • gemcitabine hydrochlorideDrug

    Also called Gemcitabine (Gemzar®) (NSC-613327)

    Gemcitabine is a fluorinated deoxynucleoside prodrug which disrupts DNA synthesis and induces apoptosis in a broad number of human tumors, including breast cancer. Gemcitabine is supplied as a lyophilized powder in sterile vials containing 200 mg of 1000 mg (1 gram) of gemcitabine as the hydrochloride salt (expressed as the free base) mannitol and sodium acetate. Dosage will be 1250mg/m2, IV pre-operatively over 30 minutes.

  • lapatinib ditosylateDrug

    Also called Lapatinib (Tykerb®) GW572016

    : Lapatinib ditosylate monohydrate tablets, 250 mg, are oval, biconvex, orange, film-coated tablets with one side of the tablet plain and other side of the tablet embossed with FG HLS. Lapatinib may also be supplied as oval, biconvex, tan tablets, with no markings. Lapatinib will be administered for at least 3 days pre-operatively at 1250mg.

  • paclitaxelDrug

    Also called Paclitaxel (Taxol®) (NSC-673089)

    Paclitaxel will be given as an intravenous infusion (80mg/m2) the morning of surgery as specified in the protocol, diluted in 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection. Paclitaxel will be administered via an infusion control device (pump) using non-PVC tubing and connectors, such as the IV administration sets (polyethylene or polyolefin) which are used to infuse parenteral nitroglycerin.

  • vinorelbine ditartrateDrug

    Also called Vinorelbine (Navelbine®) (INSC-608210)

    Vinorelbine (Navelbine®) is a unique semi-synthetic vinca alkaloid 3', 4-didehydro-4' deoxy-C'-norvincaleukoblastine (ditartrate) (IUPAC). The pyogen free, sterile parenteral dosage form is supplied in 10 mg/1 ml ampules/vials and 50 mg/5 ml vials. It will be administered at a dosage of 25mg/m2 IV over 10-30 minutes pre-operatively.

  • TrastuzumabDrug

    Also called Trastuzumab (Herceptin®) (NSC #688097)

    Trastuzumab is a monoclonal immunoglobulin G1 kappa antibody which acts as a mediator of antibody-dependent cellular cytotoxicity (ADCC) agent through its high affinity, high specificity binding to extracellular domain of HER2 Receptor. Trastuzumab is supplied as a lyophilized, sterile powder containing 440 mg trastuzumab per vial under vacuum. Each carton contains one vial of 440 mg trastuzumab and one 30 ml vial of bacteriostatic water for injection, USP, 1.1% benzyl alcohol. This will be given the morning of surgery at 2mg/m2 IV over 90 minutes.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Concentration of drug

    Serum/plasma concentrations: measured for all agents except trastuzumab by HPLC or LC-MS/MS. Trastuzumab concentrations measured by enzyme linked immunosorbent assay. Compared to tissue levels and the extent of change in serum/plasma during the surgical process will be noted.

    Tissue Concentrations: determined by HPLC/LC-MS/MS or by ELISA. The objective would be to compare tumor concentration to brain adjacent to tumor, which often has an intact BBB. The degree of BBB compromise in the specimens will be assessed through analysis of serum protein levels and hemoglobin.

    Measured: Post-Op Per Sample Collection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionApr 2013
  4. Study completionApr 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00795678
Sponsor's protocol ID
CASE4107
Other IDs
P30CA043703, CASE 4107
Status last verified
Jul 2013
First submitted
20 Nov 2008
Last updated
2 Aug 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • Morikawa A, Peereboom DM, Thorsheim HR, Samala R, Balyan R, Murphy CG, Lockman PR, Simmons A, Weil RJ, Tabar V, Steeg PS, Smith QR, Seidman AD. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro Oncol. 2015 Feb;17(2):289-95. doi: 10.1093/neuonc/nou141. Epub 2014 Jul 11.

    PubMed 25015089

Questions about this trial

What is this clinical trial studying?

An observational study of Breast Cancer and Metastatic Cancer, run by Case Comprehensive Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Concentration of drug (time frame: Post-Op Per Sample Collection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00795678, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.

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