Notice Number: NOT-CA-07-014

Key Dates
Release Date: April 16, 2007

Issued by
National Cancer Institute (NCI), (http://www.cancer.gov)

This Request for Information (RFI) is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Government, the National Institutes of Health (NIH), and the National Cancer Institute (NCI).  The NCI does not intend to award a cooperative agreement or grant on the basis of responses to this RFI or to otherwise pay for the preparation of any information submitted or for the Government's use of such information.

Description

Overview

This RFI is issued by the National Cancer Institute (NCI) to obtain information concerning collections of clinically annotated, high quality, fresh frozen childhood cancer biospecimens. Institutions/organizations that maintain such collections and would consider sharing their resources are kindly encouraged to reply to this RFI in a timely manner, i.e., by June 8, 2007, at the latest.

The requested information is needed for the initial planning stages towards the implementation of the Childhood Cancer Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative.  The TARGET program represents a Public/Private partnership between the NCI and the Foundation for the National Institutes of Health (FNIH).  Tissue collections that will be selected are intended to be eventually used in the TARGET Initiative for further characterizations, including: profiling gene expression at a high resolution; evaluating DNA segment copy number and loss of heterozygosity (LOH); and resequencing high priority genes selected in part using the gene expression and copy number data.  These data will be analyzed together in order to identify new molecular targets for development of novel therapies for these childhood cancers.  Current plans call for selecting two different childhood cancers for analysis through the TARGET Initiative.  Final plans to support tissue acquisition for the TARGET Initiative will depend upon receiving sufficient resources from the FNIH.

Background

Cancer is a genetic disease in which mutations may contribute to its initiation and progression. Researchers have already identified a large number of mutations implicated in carcinogenesis, which has led to an understanding of many details underlying tumor development and progression.  The successes of some newly introduced cancer drugs that act on known mutated proteins demonstrate that products of somatic genetic alterations are legitimate targets for therapy.  However, given complexity of cancer, it is generally assumed that only a fraction of the molecular elements involved in carcinogenesis have been identified to date.

The development of molecularly targeted therapies has been largely limited to the treatment of adult cancers.  The need for new treatment approaches for childhood cancers, however, is substantial.  The dramatic improvements in outcome seen over the last several decades have slowed, and, in many cases, current treatment approaches for childhood cancers cause serious short- and long-term side effects.  With the goal to increase benefits to children from advances in molecularly-targeted cancer therapeutics, the NCI and the FNIH have established the Childhood Cancer TARGET Initiative.

The TARGET Initiative is a public-private partnership to support the identification and validation of therapeutic targets so that new, more effective treatments can be developed for children with cancer.  Its immediate goal is to significantly advance the identification and preclinical validation of therapeutic targets for two or more childhood cancers.  FNIH will raise money from the private sector for the initiative.

While the TARGET initiative is designed to benefit children with cancer, there may also be implications for adult cancer therapeutic strategies.  The relatively simple genomic alterations of most childhood cancers may facilitate therapeutically relevant discoveries that could extend into the adult cancer setting.
Since cancer is a genetic disorder, it should be possible, in principle, to generate a catalogue of frequent mutations and other genomic abnormalities that occur in specific childhood cancers.  Once these genomic alterations are identified and functionally evaluated, an understanding of the functional consequences of these alterations can be used to develop and implement interventional strategies to eliminate and/or control cancer.

Information Requested

The following information is requested concerning each collection of biospecimens pertinent to a specific diagnosis that might potentially be available to the TARGET initiative:

1. With regard to the characteristics of each biospecimen collection, the following information is of interest:
   1. numbers of patients (unique cases) included in the collection;
   2. anatomic sites and histopathologic types (WHO classification) represented in the collection;
   3. numbers of tumors by stage and/or risk group within the collection;
   4. if known, the proportion of patients with distinctive and clinically-relevant biological subtypes (e.g., embryonal and alveolar rhabdomyosarcoma; MYCN-amplified and non-amplified neuroblastoma; etc.);
   5. proportions of the specimens that represent primary or metastatic disease;
   6. the proportion of the specimen collection that is from treatment-naïve patients;
   7. the length of follow-up for patients in the biospecimen collection (median and range); and
   8. the proportion of patients with records of a tumor-related event (e.g., failure to achieve remission, progressive disease, or tumor relapse) and the proportion of patients that are likely to have a tumor-related event recorded at the time of final follow-up for the clinical protocol(s).
      
      
2. With regard to the contents of each biospecimen collection, the following information is of interest:
   1. the percentage of biospecimens that are > 200 mg in weight;
   2. the percentage of biospecimens that are of unknown weight;
   3. the method of storage used for current and future biospecimens (e.g., fresh frozen, embedded in OCT, formalin-fixed and paraffin-embedded, and/or combinations thereof); and
   4. the existence and characteristics of any case-matched normal tissue biospecimens.
      
      
3. For biospecimens from patients treated in clinical trials, the following information is of interest: 
1. the protocol(s) on which the patients were treated;
2. whether the samples and data were or are collected as part of a “linked” or “coded” protocol (meaning that the patients can be anonymously tracked for the purpose of attaching longitudinal and outcomes data to the samples in accordance with adherence to Federal patient privacy regulations and protections); and
3. the current status of the protocol(s) from which the specimens were collected (e.g., enrolling patients; closed to accrual but in follow-up; or closed to accrual and final analysis completed).
   
   
4. With regard to the protocol(s) under which the specimens were collected, it is of interest to know whether or not the informed consent(s) included broad or narrow (i.e., specific) consent for genetic analyses of the cancer and control samples and whether limited gene resequencing focusing on cancer mutations with appropriate protections for confidentiality is allowed on the specimens. ¹
   
   
5. With regard to annotation of biospecimens, of interest are the types of demographic, clinical, and pathologic data elements associated with the specimens that are available.
   
   
6. With regard to standard operating procedures and quality control/quality assurance procedures, it is of interest to know whether the time from cut-off of blood supply to stabilization (i.e., warm ischemia time) is documented as a data element for each specimen; whether the cellular composition of each sample is documented; whether the proportion of biospecimens that are greater than 80 percent tumor is documented and, if so, what fraction of the biospecimens are greater than 80 percent tumor; and the quality control processes used to evaluate each biospecimen.
   
   
7. Biological characterization may have been performed on the biospecimens.  If gene expression profiling or copy number/LOH evaluations have been performed on the specimens, the following items are of interest: the technology and methods employed for the biological characterization;  the genomic analysis tools; and the quality control measures that were applied at all steps during the biological characterization of the specimens.

The NCI welcomes any additional information the respondent wishes to submit, such as details of repository contents, collection procedures, and biorepository management procedures.  Please attach such information as appendices to the main response.

Sending Responses to this RFI

Separate responses (not longer than ten pages) should be provided for each collection of biospecimens of a specific clinical diagnosis.  Please send all responses by e-mail to smithm@ctep.nci.nih.gov by June 8, 2007, at the latest.  

Inquiries

For questions and further information please contact:

Malcolm Smith, M.D., Ph.D.
Associate Branch Chief, Pediatrics
Cancer Therapy Evaluation Program
Division of Cancer Therapy and Diagnosis
National Cancer Institute
6130 Executive Boulevard, Room 7025, MSC 7432
Bethesda, MD 20892-7432
Rockville, MD 20852 (Overnight)
Telephone: 301-496-2522
Fax: 301-402-0557
E-mail: smithm@ctep.nci.nih.gov

Acknowledgement of receipt of responses will neither be made nor will respondents be notified of the Government's assessment of the information received.  No basis for claims against the Government shall arise as a result of a response to this request for information or the Government's use of such information as either part of our evaluation process or in developing specifications for any subsequent announcement.

¹ Because of the special status of children as research participants and of the need to be especially careful in protecting personal information in this setting, potentially identifying data related to the genetic constitution of the research participant, rather than to his/her cancer biospecimens, will be protected as extensively as possible by TARGET-specific policies and through the responsible Institutional Review Boards (IRB). 

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