Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Neoplasms

Precancerous Conditions

Uterine Cervical Dysplasia

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cervical Intraepithelial Neoplasia

fluorophotometry

colposcopic biopsy

colposcopy

light-scattering spectroscopy

Sylvia Lam

RATIONALE: New diagnostic procedures, such as spectroscopy, may be a less invasive way to check for dysplasia and neoplasia in the cervix. Spectroscopy may also used as a screening test to help doctors find cervical cancer sooner, when it may be easier to treat.

PURPOSE: This clinical trial is studying how well spectroscopy works in diagnosing dysplasia and neoplasia in the cervix in women undergoing colposcopy or Pap testing.

OBJECTIVES:

* To identify potential improvements for a noninvasive method of diagnosing dysplasia and neoplasia in the cervix using fluorescence and reflectance spectroscopy.
* To measure the reflection and fluorescence spectra in vivo of sites in the human cervix.
* To further refine fluorescence spectroscopy for detection of cervical lesions via better classification of normal columnar tissue and non-neoplastic tissue with inflammation, and low- and high-grade squamous intraepithelial lesions.
* Evaluate and validate the wavelength selections for the spectroscopy device derived from in vitro measurements.
* Determine the sensitivity and specificity of this device for the diagnosis of cervical intraepithelial neoplasia.

OUTLINE: This is a multicenter study. Patients are stratified according to menopausal status and current treatment (premenopausal not on oral contraceptive pills \[OCP\] vs premenopausal on OCP vs postmenopausal not on hormone replacement therapy \[HRT\] vs postmenopausal on HRT).

* Diagnostic study: As part of routine colposcopic evaluation, patients undergo placement of the probe on 1 to 4 sites in the cervix for 2-5 minutes. Up to two colposcopically abnormal sites and two normal sites are biopsied. Blood is drawn for hormone levels. Fluorescence excitation and emission matrix (EEM) data and reflectance spectroscopic information is acquired from patients with an abnormal Papanicolaou smear.
* Screening study: Fluorescence EEM and reflectance spectroscopic information is acquired from patients with a history of normal Papanicolaou smears.

PROJECTED ACCRUAL: A total of 800 patients with abnormal Papanicolaou smears and 1000 subjects with normal Papanicolaou smears are accrued for this study.

Spectroscopy in Diagnosing Dysplasia and Neoplasia in the Cervix in Women Undergoing Colposcopy

Measurement of Fluorescence EEM of Cervical Intraepithelial Neoplasia

National Cancer Institute (NCI)

British Columbia Cancer Agency

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cardiotoxicity

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Breast Cancer, Male

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Amino Acids

Trastuzumab

Paclitaxel

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Albumin-Bound Paclitaxel

Lapatinib

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

trastuzumab

cyclophosphamide

doxorubicin hydrochloride

lapatinib ditosylate

paclitaxel

gene expression analysis

reverse transcriptase-polymerase chain reaction

laboratory biomarker analysis

mass spectrometry

adjuvant therapy

quality-of-life assessment

Edith A. Perez, MD

Donald W. Northfeld, MD

James N. Ingle, MD

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with trastuzumab and lapatinib after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving doxorubicin together with cyclophosphamide followed by trastuzumab, paclitaxel, and lapatinib works in treating patients with early-stage HER2-positive breast cancer that has been removed by surgery.

OBJECTIVES:

Primary

* Determine the cardiac safety of adjuvant therapy comprising doxorubicin hydrochloride and cyclophosphamide followed by paclitaxel, trastuzumab (Herceptin®), and lapatinib ditosylate in patients with resected early-stage HER2-positive breast cancer.

Secondary

* Determine the adverse event profile of this regimen in these patients.
* Determine the cumulative incidence of cardiac events in patients treated with this regimen.
* Determine the LVEF in patients treated with this regimen.
* Determine the disease-free and overall survival of patients treated with this regimen.
* Compare selected quality-of-life (QOL) questionnaires in these patients.
* Evaluate QOL of patients treated with this regimen.
* Determine the cumulative incidence of pulmonary events in patients treated with this regimen.

Tertiary

* Compare Veridex CellSearch system vs quantitative reverse transcriptase polymerase chain reaction for detecting circulating tumor cells.
* Determine the relationship between serum levels of HER1 and HER2 and response to treatment.
* Evaluate cardiac markers (i.e., troponin-T, troponin-I, brain natriuretic peptide, and creatine kinase MB isoenzyme) at baseline.
* Determine the association between abnormal levels of cardiac markers and incidence of cardiac adverse events.
* Evaluate patterns of 500 metabolites in plasma in patients treated with this regimen and determine the association between metabolite patterns/molecular signatures and cardiotoxicity.
* Determine the time course of these molecular signatures and evaluate whether they are accurate predictors of cardiotoxicity that precede other evidence of cardiotoxicity (e.g., changes in left ventricular function seen by echocardiogram or MUGA scan).
* Compare metabolic signatures of cardiotoxicity with known laboratory evidence of cardiac damage (e.g., troponins or brain natriuretic peptide) in terms of sensitivity and specificity.

OUTLINE: This is a randomized, pilot, multicenter study. Patients are stratified according to educational level (less than high school vs high school or GED vs formal education beyond high school).

Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 2-3 weeks for 4 courses. Patients then receive paclitaxel IV over 60 minutes and trastuzumab (Herceptin®) IV over 90 minutes on days 1, 8, and 15 and oral lapatinib ditosylate on days 1-21. Treatment with paclitaxel, trastuzumab, and lapatinib repeats every 3 weeks for up to 4 courses. Patients then receive trastuzumab IV over 30-90 minutes on day 1 and oral lapatinib ditosylate on days 1-21. Treatment with trastuzumab and lapatinib ditosylate repeats every 3 weeks for up to 12 courses.

Patients complete Linear Anologue Self Assessment (LASA) and Symptoms Distress Scale (SDS) questionnaires, including fatigue, diarrhea, and rash assessment, at baseline, after 2-3, 5-6, and 18 months of treatment, and 5 years after completion of treatment. Patients are also randomized to 1 of 2 arms to complete additional quality of life questionnaires at these same time points.

* Arm I: Patients complete EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires.
* Arm II: Patients complete FACT-B questionnaire. Blood samples are acquired periodically throughout and at the completion of study treatment. Samples are analyzed for circulating tumor cells by Veridex CellSearch system, quantitative reverse transcriptase polymerase chain reaction, and liquid chromatography with tandem mass spectrometry, soluble HER1- and HER2-receptor concentrations, circulating cardiac markers, and metabolic markers for possible correlation with cardiac events.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 109 patients will be accrued for this study.

Doxorubicin and Cyclophosphamide Followed By Trastuzumab, Paclitaxel, and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery

Phase II Study of Cardiac Safety and Tolerability of an Adjuvant Chemotherapy Plus Trastuzumab With Lapatinib in Patients With Resected HER2 + Breast Cancer

Measured by number of patients with at least one with grade 3+, Grade 4+, Hem, and Non-Hem AEs.

Evaluable patients included those completed the AC phase of their treatment regimen; with post AC cardiac evaluation indicates they are eligible to begin treatment with PTL; and those have begun their post-AC therapy.

Cardiac events: symptomatic congestive heart failure (CHF), cardiac death and other cardiac events (NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade \>=3)

Number of Patients Who Experience \>= 10 Percent Drop in Left Ventricular Ejection Fraction (LVEF) from baseline to any post-baseline time point.

DFS was defined as the time from registration to the earliest date of documentation of any local, regional, or distant recurrence of breast cancer (BC); the development of a contralateral BC or second primary other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast; or death from any cause without the documentation of one of these events. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.

OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.

LASA score is from 0-90 with 0 being the worst and 90 being the best. SDS score is from 13-65 with 65 being the worst and 13 being the best.

Overall Symptom Distress Scale (SDS) QOL Measurement and Overall LINEAR ANALOGUE SELF ASSESSMENT (LASA) QOL Measurement

Pulmonary events to be included were grade 3 and higher pulmonary adverse events at least possibly related to study treatment, which occur at any time after post-AC treatment is begun, but prior to documentation of a breast cancer recurrence, contralateral breast cancer, secondary primary cancer, non-pulmonary death, or pulmonary death not related to study treatment.

Mayo Clinic

Adverse event data is not available on one patient, thus, only 108 patients were included in adverse events table.

Standard doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (80 mg/m\^2) x 12 with concurrent standard dose trastuzumab (weekly x 12, then repeat 3 weeks for an additional 9 months) plus daily lapatinib (modified to 750 mg during Paclitaxel + Trastuzumab + Lapatinib (PTL) and 1000 mg during trastuzumab + lapatinib (TL)) for a total of 12 months.

AC/PTL

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Performance Status Grade:

0=Fully active, able to carry on all predisease activities without restriction (Karnofsky 90-100); 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work (Karnofsky 70-80).

Eastern Cooperative Oncology Group (ECOG) performance status

T1=Tumor <=2 cm (3/4 of an inch) across

T2=2cm < Tumor <5 cm across

T3=Tumor > 5 cm across

Missing

T Stage

SLN+ without full axillary dissection

N0=Node negative (either by negative sentinel node or by axillary dissection); N1=Node positive (axillary nodal dissection with 1-3 + nodes); N2=Node positive (axillary nodal dissection with 4-9 + nodes); N3=Node positive (axillary nodal dissection with 10+ nodes); SLN+ refers to Positive Sentinel Node

Nodal Status

Estrogen and/or Progesterone Positive

Estrogen and Progesterone Negative

Hormonal Status

FISH Amp/IHC Pos

FISH Amp/IHC Neg

FISH Not Amp/IHC Pos

FISH Not Done/IHC Pos

FISH Amp/IHC refers to fluorescence in situ hybridization amplification/immunohistochemistry

HER2 Status - Positive

Left Ventricular Ejection Fraction (LVEF) Measurement

Never

Former

Current

Smoking status

Current use of hypertensive medication

History of diabetes

Premenopausal

Perimenopausal

Postmenopausal

Menopausal status

Less than high school

High school

Beyond high school

Education level

Dr. Edith A. Perez

Number of Patients With Congestive Heart Failure (CHF) While on Active Treatment

Grade 3+ Adverse Event

Grade 4+ Adverse Event

Grade 3+ Hem Adverse Event

Grade 4+ Hem Adverse Event

Grade 3+ Non-Hem Adverse Event

Grade 4+ Non-Hem Adverse Event

Adverse Event Profile as Measured by NCI CTCAE v 3.0

Cumulative Incidence (CI) of Cardiac Events

Drop ≤ 10 between any 2 time points

Drop ≥ 10 between any 2 time points

Number of Patients Who Experience >= 10 Percent Drop in Left Ventricular Ejection Fraction (LVEF)

Percentage of Participants With Disease-Free Survival (DFS)

Percentage of Participants With Overall Survival (OS)

LASA Time from Cycle 5 Baseline (Months 2-3)

LASA Time from Cycle 5 Baseline (Months 5-6)

LASA Time from Cycle 5 Baseline (Month 18-Year 3)

LASA Time from Cycle 5 Baseline (Year 4-5)

SDS Time from Cycle 5 Baseline (Months 2-3)

SDS Time from Cycle 5 Baseline (Months 5-6)

SDS Time from Cycle 5 Baseline (Month 18-Year 3)

SDS Time from Cycle 5 Baseline (Year 4-5)

Number who completed the QOL questions for each Timeframe.

Change in Overall LINEAR ANALOGUE SELF ASSESSMENT (LASA) and Change in Symptom Distress Scale (SDS) Overall QOL

LASA Time from Cycle 5 Baseline (Month 18-3 Year)

Proportion of Patients Experienced a Significant Decline in LINEAR ANALOGUE SELF ASSESSMENT (LASA) and a Overall Symptom Distress Scale (SDS) QOL Measurements

No patients experienced grade 3 or higher pulmonary adverse events at least possibly related to study treatment after at any time after post-AC treatment began.

Incidence of Pulmonary Events

Overall Study

Mouth and Tooth Diseases

Head and Neck Neoplasms

Mouth Neoplasms

Oral Cancer

Laryngeal Cancer

Hypopharyngeal Cancer

Lip and Oral Cavity Cancer

Dermatologic Agents

Central Nervous System Depressants

Dihematoporphyrin Ether

Trioxsalen

Hematoporphyrin Derivative

Ether

Photosensitizing Agents

porfimer sodium

Wesley L. Hicks, MD

RATIONALE: Drugs that make cancer cells more visible to light may help in the diagnosis of head and neck cancer.

PURPOSE: Phase II trial to study the usefulness of porfimer sodium in diagnosing patients with head and neck cancer.

OBJECTIVES: I. Determine whether porfimer sodium fluorescence can be used to reveal early malignant changes in patients with lesions of the oral cavity. II. Investigate whether porfimer sodium fluorescence can define areas of field cancerization in the oral mucosa, specifically satellite foci of malignant cells within the margins of an excision. III. Determine whether uptake of fluorescence is indicative of disease stage.

OUTLINE: Patients receive porfimer sodium IV bolus and are kept in subdued light until examination with a fluorescence photometer 48 hours later. Patients must avoid sunlight and other intense lights for an additional 30 days.

PROJECTED ACCRUAL: 20 patients will be accrued per year.

Porfimer Sodium in Diagnosing Patients With Head and Neck Cancer

Pilot Study for the Diagnosis of Head and Neck Cancer: Photofrin and Visible Light

Roswell Park Cancer Institute

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Spectroscopy in Diagnosing Dysplasia and Neoplasia in the Cervix in Women Undergoing Colposcopy	NCT00632190	Cervical Cancer Precancerous Co...	fluorophotometr... colposcopic bio... colposcopy light-scatterin...	18 Years -	National Cancer Institute (NCI)
Spectroscopy in Diagnosing Dysplasia and Neoplasia in the Cervix in Women Undergoing Colposcopy	NCT00632190	Cervical Cancer Precancerous Co...	fluorophotometr... colposcopic bio... colposcopy light-scatterin...	18 Years -	National Cancer Institute (NCI)
Doxorubicin and Cyclophosphamide Followed By Trastuzumab, Paclitaxel, and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery	NCT00436566	Breast Cancer Cardiac Toxicit...	trastuzumab cyclophosphamid... doxorubicin hyd... lapatinib ditos... paclitaxel gene expression... reverse transcr... fluorophotometr... laboratory biom... mass spectromet... adjuvant therap... quality-of-life...	18 Years - 120 Years	Mayo Clinic
Porfimer Sodium in Diagnosing Patients With Head and Neck Cancer	NCT00002964	Head and Neck C...	porfimer sodium fluorophotometr...	18 Years -	Roswell Park Cancer Institute

Spots Global Cancer Trial Database for fluorophotometry