# Presentation: 506893

## Pediatric Oncology Subcommittee of ODACReport of Meeting October 20, 2005 

**Pamela J. Haylock, RN, MA**
- Consumer  Representative
- presenting on behalf of
**Gregory H. Reaman, MD**
** ****Subcommittee Chair**

## Subcommittees

- Subcommittees are advisory to the “parent” committee
- do not directly advise FDA
- Parent committee reviews subcommittee recommendations; advises FDA
- At least 2 members of parent committee serve on the subcommittee
- No charter or official roster* *

## Pediatric Subcommittee to ODAC BPCA– Sec 15 

- Evaluate and to the extent practicable, prioritize new and emerging therapeutic alternatives to treat pediatric cancer
- Provide recommendations and guidance to ensure that children with cancer have timely access to the most promising new cancer therapeutics
- Advise on ways to improve consistency in the availability of new therapeutic agents

## Pediatric Subcommittee Members & Consultants for the October 20, 2005 Meeting

**From ODAC:**
**Gregory H. Reaman, MD, Chairperson**
- 	Pediatric Oncology & Chair, COG
- 	Prof Pediatrics, GWU, School of Medicine
- 	Washington, D.C.
**Pamela Haylock, RN, MA**
- 	Consumer Representative to ODAC
- 	Oncology Consultant & Doctoral Student
- 	UTMB Graduate School of Biomedical Sciences
- 	Galveston, TX

## Consultants

**Jeffrey Barrett, PhD**
- 	Assoc. Prof, Pediatrics, Children’s Hospital of Philadelphia
**James Boyett, PhD**
- 	Dept. Biostatistics
- 	St. Jude Children’s Research Hospital,  Memphis, TN
**Jerry Finklestein, MD**
- 	Jonathan Jacques Children’s CA Center
- 	Long Beach, CA

**Michael Link, MD**
- 	Stanford, School of Medicine
- 	Division of Hematology
- 	Stanford, CA
**Charles Reynolds, MD**
- 	Children’s Hosp of LA/USC
- 	Los Angeles, CA
**Victor Santana, MD**
**	**Dept Hematology Oncology
**	**St. Jude, Children’s Research Hospital, Memphis, TN

## Consultants

**  ****Cindy Schwartz, MD**
-     Rhode Island Hospital
-     Dept. Pediatrics - Hem/Onc
-     Providence, RI
**  ****Malcolm Smith, MD, PhD**
-     Head, Ped Section, CIB
-     CTEP, NCI
**  ****Clinton Stewart, PhD**
**  ****St. Jude Children’s Research      **
**  ****Hospital**
**  ****Memphis, TN**

**Thomas Walsh, MD**
- 	Chief, Immunocompromised Host Section, NCI
**Naomi Winick, MD**
**	**Dept. Pediatrics – Hem/Onc
- 	UT, Southwestern Med Ctr
- 	Dallas, TX

## Consultants

**Marilyn S. Eichner **–** **Rockville, MD
- 	Patient Representative
**Cathy A. O’Connell** – Belchertown, MA
- 	Patient Representative
**Eugene Sun, M.D**.
- 	Industry Representative
- 	Global Pharmaceutical Development
- 	Abbott Laboratories, Abbot Park, IL

## FDA Participants

- Richard Pazdur, MD
- 	Director, Office of Oncology Products
- Karen Weiss, MD
- 	Deputy Director, Office of Oncology Products
- Patricia Keegan, MD
- 	Director, Div of Biologic Oncology Products
- Robert Justice, MD
- 	Acting Director, Division of Oncology Drug Products
- Ramzi Dagher, MD
- 	Medical Team Leader, Division Oncology Drug Products

## FDA Participants

- Joseph Gootenberg, MD
- 	Medical Team Leader, Divsion of Pediatric Drug Development
- Lisa Mathis, MD
- 	Acting Director, Division of Pediatric Drug Development
- 	Office of Counterterrorism & Pediatrics
- Martin Cohen, MD
- 	Medical Officer, Division of Oncology Drug Products
- Jeff Summers, MD
- 	Medical Officer, Division of Biologic Oncology Products
- Anne Zajicek, MD, NIH
- Victoria Ferretti-Aceto, PharmD, Executive Secretary

## Pediatric Initiatives

- Pediatric Research Equity Act, December 3, 2003
- Best Pharmaceuticals for Children Act, January 4, 2002
-    ***Both laws are intended to support and encourage drug development in the pediatric population***

## Pediatric Research Equity Act(PREA)

- One of two laws intended to promote the study of drugs and biologics in pediatric patients
- Studies prevent pediatric patients from being a “study of one”
- Studies in the pediatric population are REQUIRED, but only for the indication that was studied in adults

## Best Pharmaceuticals for Children Act (BPCA)

- In pediatric oncology
- prioritize new drugs for study
- assure timely access to new treatments
- develop pre-clinical models of pediatric cancers

## Why both PREA and BPCA?

- Distinction between the scope of studies requested under BPCA and required under PREA
- PREA specific to indication in submission
- BPCA can ask for “off-label” indications

## Open Public Hearing Speaker

**Sadhana Dhruvakumar**
- Director, Medical Products Testing
- People for the Ethical Treatment of Animals
**Animal Use in Drug Development**

## Questions from NIH to the Pediatric Subcommittee of the Oncologic Drug Advisory Committee

- What type of prioritization process should be used for deciding which off-patent drugs should be studied?
- What is the definition of health benefit?
- Number of patients affected
- Lack of other drugs that treat the disease
- Severity of the disease

## Questions

- Are there other drugs that should be studied?
- Antineoplastics
- Supportive Care
- Anti-emetics
- Anti-infectives
- Analgesics
- Other

## Issues in post-marketing studies for clofarabine (ClolarTM) 

- Feasibility of proposed populations (ALL, 1st or 2nd relapse) & primary endpoint (4 mo EFS)?
- Design’s likelihood to permit adequate assessment of clinical benefit?
- Can data generated in adults support efficacy in pediatric ALL patients?

## Issues in post-marketing studies for clofarabine (ClolarTM) 

*Adult populations & primary efficacy endpoints *_*do not*_* permit adequate assessment of clinical benefit. Suggest focus on 1**st** relapse, known active agents in controlled setting. Remission induction &/or MRD are potential primary endpoints.*
*It is not plausible that Adult AML data supports efficacy in pediatric ALL patients based on current knowledge of disease biologies *

## Issues in post-marketing studies for pegfilgrastim (Neulasta®)

- Will Amgen’s study in patients with sarcoma treated with VAdriac/IE allow for extrapolation of activity and safety findings across all age groups and different pediatric cancers?

## Issues in post-marketing studies for pegfilgrastim (Neulasta®)

*Difficulty enrolling this population of patients (esp. younger ages) in these studies*
*Difficulty administering filgrastim in randomized settings*
*Competition with other studies where protocols demand growth factors*

## Issues in post-marketing studies for pegfilgrastim (Neulasta®)

*Suggestions:*
*Patients serve as own controls*
*Randomize for the first cycle*
*Consider studies in patients with rhabdomyosarcoma & neuroblastoma to enhance age range of subjects*

## Issues in post-marketing studies for palifermin (Kepivance®)

- Suitability & feasibility of need for dose escalation;
- Need for pharmacokinetic data
- Choice of patient population (homogenous Vs heterogeneous r/t underlying disease, source of stem cells, cytotoxic regimen, etc.)

## Issues in post-marketing studies for palifermin (Kepivance®)

*Need data from pediatric populations:*
*Suggest decreasing # of doses tested in dose escalation portion*
*Consider evaluating other schedules*
*Suggest study in pts with acute leukemia receiving allogeneic transplant would be useful, feasible*
*Population could be both autologous & allogeneic transplant recipients*
*Use adult PK data as a guideline for when/how to sample, but only as a framework for ped dosing*

## Ongoing studies of vincristine & actinomycin-D

- Approach to safety/efficacy & PK data
- Are there additional data that should be collected?
- Could frequency of toxicity be minimized with dose cap?
- Would dose-capping cause underdosing & subsequent lack of efficacy
- Application of mathematical models for dose finding?

## Ongoing studies of vincristine & actinomycin-D

*VCR: difficult to quantify toxicity*
*Lack of standard assessments & scoring for peripheral neuropathy*
*Required tests for measuring or monitoring?*

## Off-patent BPCA Process

- Could additional labeling data to provide health benefits for pediatric patients r/t off-patent drugs and/or therapeutic drug classes?

## Off-patent BPCA Process

*Need dose adjustment guidelines for many off-patent drugs, specifically in obese children*
*Administration methods to decrease toxicity – eg., less frequent dosing intervals*
*Dose-optimization via systematic methods*
*Tools to measure early toxicity*
*Arbitrary age groups (suggesting 2 age ranges during first year of life, then 1-5 & 5-10)*

## Suggested topics for future ODAC Pediatric Subcommittee Meetings

- Pain control
- Symptom management in neonates
- Drug delivery systems
- Long term sequelae
- Orphan drug indications
- End of life & palliative care
- Indications waived from the requirement for conducting pediatric studies

## Suggested topics for future ODAC Pediatric Subcommittee Meetings

- Role of stable disease as an endpoint
- Endpoints for pediatric cancer
- Pre-clinical predictors of clinical outcomes
- Re-formulations, rounding off errors
- Past 7 years (post PREA & BPCA): any changes in getting drugs to pediatric cancer patients earlier?

## Suggested next meeting of ODAC Pediatric Subcommittee: 

- Suggested next meeting of ODAC Pediatric Subcommittee:
- First quarter 2006