Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Dactinomycin

molecular genetic technique

mass spectrometry

pharmacological study

Fin Breatnach, MD, FRCPE

Martin W. English, MD

Pamela Kearns, MD

Amos Burke, MD

Adam Glaser, MD

Mabrouk Madi, MD

Heather P. McDowell, MD

Ananth Shankar, MD

Gill Levitt, MD

Bernadette Brennan, MD

Juliet Hale, MD

Gareth Veal

Martin Hewitt, MD, BSc, FRCP, FRCPCH

Kate Wheeler, MD

Mary P. Gerrard, MBChB, FRCP, FRCPCH

Janice A. Kohler, MD, FRCP

Mary Taj, MD

Anthony McCarthy, MD

Veronica Neefjes

W. Hamish Wallace, MD

Milind D. Ronghe, MD

Heidi Traunecker, MD, PhD

Alan Boddy, PhD

RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving dactinomycin may help doctors learn how dactinomycin works in the body and how patients will respond to treatment.

PURPOSE: This laboratory study is evaluating the pharmacokinetics of dactinomycin in young patients with cancer.

OBJECTIVES:

* Determine the pharmacokinetics (PKs) of dactinomycin in pediatric patients with cancer.
* Determine the degree of interpatient variation in the PKs of this drug.
* Determine the influence of characteristics such as age, tumor type, and concurrent therapy on drug PKs in these patients.
* Correlate drug PKs with clinical response and toxicity observed in these patients, focusing particularly on the incidence of severe liver toxicity or veno-occlusive disease.
* Correlate pharmacogenetic variability with clinical and PK data.

OUTLINE: This is a multicenter study.

Patients undergo blood collection for pharmacokinetic sampling of dactinomycin at baseline (prior to the initiation of dactinomycin) and periodically during course 1 of chemotherapy. An additional blood sample is obtained before or after treatment for the collection of peripheral blood lymphocytes. DNA from these cells is isolated and investigated for genetic variation in genes relevant to the pharmacology of dactinomycin. Plasma concentrations of dactinomycin are determined by liquid chromatography mass spectrometry analysis.

Patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Pharmacokinetics of Dactinomycin in Young Patients With Cancer

Pharmacokinetics of Actinomycin D in Children With Cancer

Children's Cancer and Leukaemia Group

Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Rare Diseases

Recurrence

Carcinoma, Renal Cell

Wilms Tumor

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms by Histologic Type

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Renal Cell Carcinoma

Wilms' Tumor

polymerase chain reaction

polymorphism analysis

Gail E. Tomlinson, MD, PhD

RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at DNA variations in the RASSF1A gene in young patients with Wilms' tumor.

OBJECTIVES:

Primary

* Determine the presence of the A133S polymorphism in the RASSF1A tumor suppressor gene by screening germline DNAs of children with Wilms' tumor.
* Determine the inheritance pattern of the A133S polymorphism by evaluating the parents of children who carry this polymorphism.

Secondary

* Determine the differences in age at diagnosis, stage, histology, site of primary tumor, and outcome, between patients with vs without the A133S polymorphism.
* Determine whether the S131F RASSF1A variant is a true polymorphism in these patients.
* Determine the polymorphic differences in this gene between these patients based on ethnicity and sex.

OUTLINE: This is a multicenter study. Patients are stratified according to age at diagnosis, stage, histology, site of primary tumor, and outcome.

Genomic DNA samples are purified from peripheral blood of patients and controls and analyzed by polymerase chain reaction for the RASSF1A gene. DNA is also analyzed from parents of patients with the A133S polymorphism.

PROJECTED ACCRUAL: A total of 471 participants (229 Wilms' tumor patients and 200 control participants plus 42 parents) will be accrued for this study.

DNA Variations in the Gene in Young Patients With Wilms' Tumor

The Incidence, Inheritance, and Prognostic Significance of Polymorphisms in the RASSF1A Gene in Children With Wilms Tumors

National Cancer Institute (NCI)

Children's Oncology Group

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Congenital Abnormalities

Leukemia, Myelomonocytic, Acute

Leukemia, Monocytic, Acute

Leukemia, Erythroblastic, Acute

Leukemia, Megakaryoblastic, Acute

Leukemia, Basophilic, Acute

Leukemia, Eosinophilic, Acute

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Acute Monoblastic Leukemia

Acute Myelomonocytic Leukemia

Acute Erythroid Leukemia

Di Guglielmo's Syndrome

Acute Megakaryoblastic Leukemia

Acute Myeloblastic Leukemia Without Maturation

Acute Myeloblastic Leukemia With Maturation

Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760.

gene expression analysis

protein expression analysis

diagnostic laboratory biomarker analysis

Maria R. Baer, MD

This research trial studies multidrug resistance genes in patients with acute myeloid leukemia. Studying samples of bone marrow or blood from patients with cancer in the laboratory may help doctors learn more about changes that may occur in deoxyribonucleic acid (DNA) and identify biomarkers related to cancer. It may also help doctors learn more about drug resistance and how patients respond to treatment.

PRIMARY OBJECTIVES:

I. To investigate the association of common single nucleotide polymorphisms (SNPs) and haplotypes of the three multidrug resistance (MDR) genes with treatment outcome in the clinical studies.

II. To assess the effect of ATP-binding cassette (ABC) B1, ABCC1, and ABCG2 polymorphisms and haplotypes on treatment outcome in younger patients enrolled on Cancer and Leukemia Group B (CALGB) 9621 and 19808.

III. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on treatment outcome in older patients enrolled on CALGB 9720.

SECONDARY OBJECTIVES:

I. To test the hypothesis that ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes are associated with phosphoglycolate phosphatase (Pgp), multidrug resistance protein 1 (MRP-1), and ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group) (BCRP) function and expression in pre-treatment blasts from acute myeloid leukemia (AML) patients.

II. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on PGP, MRP-1, and BCRP function through CALGB 9760 in younger patients enrolled on CALGB 9621 and 19808.

III. To assess the effect of ABCB1, ABCC1, and ABCG2 polymorphisms and haplotypes on PGP, MRP-1, and BCRP function through CALGB 9760 in older patients from CALGB 9720.

IV. To conduct an exploratory analysis of the association of additional candidate genes relevant to etoposide, cytarabine, and daunorubicin with chemotherapy response and toxicity.

OUTLINE:

Leukemia blast cells obtained from bone marrow aspirate or peripheral blood at diagnosis are used to study polymorphisms and haplotypes of ATP-binding cassette (ABC) B1, ABCC1, ABCG2, and other candidate genes. Multidrug resistance (MDR) protein expression and function are also analyzed using leukemia blast cells from patients enrolled on CALGB-9760.

PROJECTED ACCRUAL: Tissue samples from over 600 patients will be accrued for this study.

Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia

Multidrug Resistance Protein Gene Polymorphisms in Acute Myeloid Leukemia. A CALGB Leukemia Tissue Bank Project

Alliance for Clinical Trials in Oncology

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Laryngeal Diseases

Laryngeal Cancer

Hypopharyngeal Cancer

Metastatic Squamous Neck Cancer With Occult Primary

Docetaxel

Carboplatin

Fluorouracil

Cetuximab

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Immunological

cetuximab

carboplatin

cisplatin

docetaxel

fluorouracil

fluorescence in situ hybridization

reverse transcriptase-polymerase chain reaction

immunoenzyme technique

immunohistochemistry staining method

laboratory biomarker analysis

biopsy

3-dimensional conformal radiation therapy

intensity-modulated radiation therapy

Jan B. Vermorken, MD, PhD

RATIONALE: Monoclonal antibodies, such as cetuximab, 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. Cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high energy x- rays to kill tumor cells. Cetuximab may also make tumor cells more sensitive to radiation therapy. 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. It is not yet known which regimen of radiation therapy, combination chemotherapy, and cetuximab and is most effective in treating patients with head and neck cancer.

PURPOSE: This randomized phase II trial is comparing two different regimens of radiation therapy given together with combination chemotherapy and cetuximab to see how well they work in treating patients with newly diagnosed stage III or stage IV head and neck cancer that cannot be removed by surgery.

OBJECTIVES:

* To determine the safety profile of chemoradiotherapy with carboplatin vs cisplatin in patients with newly diagnosed, unresectable stage III or IV squamous cell carcinoma of the head and neck.
* To select one of these chemoradiotherapy regimens to be used as an experimental arm in a future phase III trial.
* To look for EGFR expression and downstream signaling in reacting skin samples from patients experiencing skin toxicity and in normal skin samples from the same patients for comparison with skin samples from patients who have not shown skin toxicity.
* To explore which factors related to EGFR predict the biological activity of cetuximab in patients treated with these regimens.

OUTLINE: This is a multicenter study.

Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously over 24 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of unacceptable toxicity.

Within 3 weeks after completion of induction chemotherapy or within 5 weeks from the start of the last chemotherapy course (day 21), patients are stratified by institution and treatment response (stable disease \[SD\], partial response \[PR\], or complete response \[CR\] vs non-response \[progressive disease\]). Patients with progressive disease are removed from study and patients with SD, PR, or CR are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo radiotherapy (RT) (3-dimensional conformal RT or intensity-modulated RT) on days 1-5 weekly for up to 7 weeks. Beginning on day 1 of RT, patients receive cisplatin IV over 1 hour once weekly for up to 7 weeks.
* Arm II: Patients undergo RT as in arm I. Beginning on day 1 of RT, patients receive carboplatin IV over 1 hour once weekly for up to 7 weeks.

Patients in both arms receive cetuximab IV over 1-2 hours once weekly beginning on day 1 of induction chemotherapy and continuing until the end of concurrent chemoradiotherapy.

Primary tumor tissue and skin biopsies, including fixed paraffin-embedded tissue specimens or frozen tissue, are collected at baseline (prior to treatment) and after completion of study treatment for correlative laboratory studies of EGFR expression and downstream signaling. Specimens are assessed by immunohistochemistry, fluorescence in situ hybridization, and reverse transcriptase-PCR sequencing of genes and proteins for ErbB-related activation. In the event of skin toxicity during treatment, patients undergo at least two additional biopsies, one in reacting skin and one in normal skin. Samples are assessed for markers of treatment efficacy related to cetuximab.

After completion of study therapy, patients are followed at 3 months and periodically thereafter.

Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Head and Neck Cancer That Cannot Be Removed By Surgery

Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies

European Organisation for Research and Treatment of Cancer - EORTC

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Hereditary Melanoma

Neuroendocrine Tumor

Neuroepithelioma

microarray analysis

mutation analysis

mutation carrier screening

study of high risk factors

Julia Newton Bishop, MD

RATIONALE: Identifying gene mutations and other risk factors in patients with melanoma and in families with a history of hereditary melanoma may help doctors identify persons at risk for melanoma and other types of cancer. It may also help the study of cancer in the future.

PURPOSE: This clinical trial is studying gene mutations in patients with melanoma and in families with a history of hereditary melanoma.

OBJECTIVES:

* Determine the incidence and etiologic significance of variants of known melanoma susceptibility genes (MSGs) in families with multiple cases of melanoma.
* Determine the proportion of multiple-case families that are explained by high-penetrance mutations in known MSGs.
* Determine the proportion of multiple-case families that are explained by these mutations and whether it varies with latitude, as a surrogate for ultraviolet exposure, with number of affected relatives, with average age at onset of melanoma in relatives, with presence of multiple primary melanoma, or with other family-specific variables.
* Determine the penetrance of MSG mutations in these families.
* Determine if the penetrance varies with age, sex, or birth cohort.
* Determine if the penetrance varies with the gene involved or nature of the mutation.
* Assess the penetrance in mutations that also have a deleterious effect on the alternative splice product, p14ARF.
* Determine whether carriers of MSGs have an increased susceptibility to other types of cancer.
* Determine the risk of other types of cancers for mutation carriers.
* Determine environmental exposures, in particular sun exposure, that modify risk of melanoma in MSG mutation carriers.
* Determine the cutaneous phenotypes that correlate with melanoma risk in these families.
* Correlate cutaneous phenotypes with the presence of MSG variants.
* Determine the effect of other covariates, such as sun exposure or the presence of alleles of putative modifying genes (e.g., MC1R or CDKN2A), on phenotype.
* Determine if modifier genes, such as those controlling pigmentation of the skin, and therefore sun susceptibility, modify risk in MSG mutation carriers.
* Identify any histopathological correlates of MSG status in primary tumors arising in melanoma-susceptible individuals in these families.
* Identify any histopathological correlates of primary melanomas in carriers of MSG mutations with other covariates.

OUTLINE: This is a case-control, multicenter study.

Participants complete 2 questionnaires and assist in the creation and expansion of a family pedigree. Blood samples are examined for melanoma susceptibility gene mutations, including CDK4 and CDKN2A.

Participants are also examined for moles and photographed. Physical variables (e.g., skin, eye, and hair pigmentation) and sun damage (solar lentigines and freckling) are also noted.

If available, tissue samples are examined for Clark level, Breslow thickness, and frequency of mitoses. Peri-lesional skin from tumors is examined by p53 staining.

Participants are followed periodically to monitor cancer development.

Peer reviewed and funded or endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 5,000 participants will be accrued for this study.

Identifying Gene Mutations in Patients With Melanoma and in Families With a History of Hereditary Melanoma

Studies of Familial Melanoma

Leeds Cancer Centre at St. James's University Hospital

Peripheral blood and bone marrow samples are analyzed to assess gene expression using polymerase chain reaction (PCR) or reverse transcriptase-PCR assays and microarray assays. Genes to be studied include BAALC, ERB, EVI1, MLL, FLT3, NPM1, and CEBPA.

Guido Marcucci, MD

RATIONALE: Collecting and storing samples of tissue and blood from patients with cancer to study in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.

PURPOSE: This laboratory study is looking at changes in the DNA of tissue samples that were collected from patients with acute myeloid leukemia.

OBJECTIVES:

* Validate, on the larger number of patients with karyotypically normal acute myeloid leukemia (AML) treated uniformly on CALGB-19808, preliminary results from CALGB-9621 showing that BAALC and ERG overexpression and microarray gene-expression signatures can stratify the patients prognostically.
* Establish whether microRNAs are differentially expressed in subsets of patients with AML and normal cytogenetics, and, if so, attempt to identify a signature that stratifies patients prognostically.
* Explore the relative contribution in predicting clinical outcome of patients with cytogenetically normal AML using genetic markers such as BAALC, ERG, and EVI1 overexpression, MLL partial tandem duplication, FLT3 internal tandem duplication, NPM1 and CEBPA mutations, and microarray gene expression microRNA signatures.

OUTLINE: This is a multicenter, pilot study.

Peripheral blood and bone marrow samples are analyzed to assess gene expression using polymerase chain reaction (PCR) or reverse transcriptase-PCR assays and microarray assays. Genes to be studied include BAALC, ERB, EVI1, MLL, FLT3, NPM1, and CEBPA.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Genetics Study of Tissue Collected From Patients With Acute Myeloid Leukemia

Molecular Genetic Studies of Acute Myeloid Leukemia (AML) With Normal Cytogenetics. A CALGB Leukemia Tissue Bank Project

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacokinetics of Dactinomycin in Young Patients With Cancer	NCT00900354	Unspecified Chi...	molecular genet... mass spectromet... pharmacological...	- 21 Years	National Cancer Institute (NCI)
DNA Variations in the Gene in Young Patients With Wilms' Tumor	NCT00088803	Kidney Cancer	molecular genet... polymerase chai... polymorphism an...	- 18 Years	Children's Oncology Group
Multidrug Resistance Genes in Patients With Acute Myeloid Leukemia	NCT00898456	Leukemia	gene expression... molecular genet... polymorphism an... protein express... diagnostic labo...	15 Years -	Alliance for Clinical Trials in Oncology
Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Head and Neck Cancer That Cannot Be Removed By Surgery	NCT00646659	Head and Neck C...	cetuximab carboplatin cisplatin docetaxel fluorouracil fluorescence in... molecular genet... reverse transcr... immunoenzyme te... immunohistochem... laboratory biom... biopsy 3-dimensional c... intensity-modul...	18 Years - 75 Years	European Organisation for Research and Treatment of Cancer - EORTC
Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Head and Neck Cancer That Cannot Be Removed By Surgery	NCT00646659	Head and Neck C...	cetuximab carboplatin cisplatin docetaxel fluorouracil fluorescence in... molecular genet... reverse transcr... immunoenzyme te... immunohistochem... laboratory biom... biopsy 3-dimensional c... intensity-modul...	18 Years - 75 Years	European Organisation for Research and Treatment of Cancer - EORTC
Pharmacokinetics of Dactinomycin in Young Patients With Cancer	NCT00900354	Unspecified Chi...	molecular genet... mass spectromet... pharmacological...	- 21 Years	National Cancer Institute (NCI)
Identifying Gene Mutations in Patients With Melanoma and in Families With a History of Hereditary Melanoma	NCT00450593	Hereditary Mult... Melanoma (Skin)	gene expression... microarray anal... molecular genet... mutation analys... laboratory biom... mutation carrie... study of high r...	-	National Cancer Institute (NCI)
Genetics Study of Tissue Collected From Patients With Acute Myeloid Leukemia	NCT00898092	Leukemia	microarray anal... molecular genet... mutation analys... polymerase chai... reverse transcr... diagnostic labo...	15 Years - 59 Years	Alliance for Clinical Trials in Oncology

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