Clinical Trials that Address Health Care Disparities Daniel G. Petereit, MD Department of Radiation Oncology University of Wisconsin Medical School University

Clinical Trials that Address Health Care Disparities

Daniel G. Petereit, MD

Department of Radiation Oncology

University of Wisconsin Medical School

University of South Dakota Medical School

Rapid City, South Dakota

e-mail: [email protected]

John T. Vucurevich Cancer Care InstituteJohn T. Vucurevich Cancer Care Institute

RAPID CITYREGIONAL HOSPITALRAPID CITYREGIONAL HOSPITAL

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Historical background– Minority mistrust research

CDRP Trials– Cooperative Group– CDRP trials– Other: behavioral, molecular

Successful Recruitment Clinical Trials Future trials

Tuskeegee Syphilis StudyPurpose: To observe the natural history of syphilis

Subjects: African American men in rural Alabama (N=405, 1932-72)

Men diagnosed with syphilis were enrolled and examined periodically, but not given treatment for their disease

Treatment was withheld to preserve the study even after it became generally available

No informed consent for participants

Removal Policy: Eastern Tribes

“Trail of Tears”

Trail of Tears

• Federal relocation program of American Indians to Oklahoma

• 1830-1860• Majority relocated under President Andrew Jackson

• 60 Tribes, including 5 “civilized tribes”

• Tens of Thousands died in route

• Historical trauma

• Massacre at Wounded Knee, SD– Recent memory?

1960-1970s Sterilization of AI Women

American Indian women were sterilized at selected IHS clinics during the 1960s and 1970s

3,406 sterilizations in 3 IHS Areas between 1973 and 1976

No informed consent, no 72H waiting period, no right to withdraw

• US Department of Health, Education, and Welfare, Office of the Secretary “Sterilization Guidelines,” Federal Register 38 August 3, 1973; pp. 20 930-31 and September 21, 1973, pp. 26 459-61. Also Federal Register 39 April 18, 1974. pp.13 873

• Government Accounting Office (GAO), Comptroller of the United States, Investigations of Allegations Concerning Indian Health Services; Washington, DC. US Government Printing Office, November 4, 1976.

Native American Cancer Research http://www.NatAmCancer.org

Linda Burhansstipanov, MSPH, DrPH

http://www.natamcancer.org/

CDRP: Supporting the Nation’s Goal of Eliminating Cancer Health Disparities

• Increase minority access to and participation in radiation oncology clinical trials

• Increase the number of clinical and translational scientists studying cancer disparities

• Develop new institutions’ ability to engage in long-term research efforts

• Investigate new areas of health disparities research



CDRP Trials– Cooperative Group

• RTOG, ECOG, NSABP, NCCTG, GOG– CDRP trials: PI initiated– Other: behavioral, molecular


Successful Cooperative Group Trials: Recruitment CDRP Sites

• NSABP 35: anastrozole vs tamoxifen in postmenopausal DCIS patients undergoing lumpectomy & radiation therapy

• RTOG 245: PET pre and post treatment assessment for locally advanced NSCLC

• RTOG 0315: Phase III Study to Determine the Efficacy of Octreotide in Reducing Severity of CT/XRT-Induced Diarrhea Anal or Rectal Cancer

• RTOG 0321: Phase II Trial of HDR and EBRT Prostate CA

• NSABP, CALBG Breast cancer studies that include a radiation component

Moderately Successful Cooperative Group Trials: Recruitment CDRP Sites

• RTOG 9804: Phase III Trial Observation +/- Tamoxifen vs. RT +/- Tamoxifen for Good Risk DCIS

• NSABP B-39: Phase III Trial WBRT vs APBI

• RTOG 0232: A Phase III Study EBRT & PSI vs PSI Alone for Intermediate Risk Prostate CA Carcinoma

• NCIC MA20: A Phase III Study of Regional Radiation Therapy in Early Breast Cancer

• RTOG 0247: Phase II Trial of Neoadjuvant Combined Modality Therapy for Locally Advanced Rectal Cancer

Moderately Successful Cooperative Group Trials: Recruitment CDRP Sites

• RTOG 0433: Phase III Trial of Single Versus Multiple Fractions for Re-Irradiation of Painful Bone Metastases

• RTOG 0215: Treatment of Erectile Dysfunction in Patients Treated with Neoadjuvant Androgen Suppression and Radiotherapy for Prostate Cancer: Impact on Patient and Partner Quality of Life

• RTOG 9813: Phase III Study of EBRT & TMZ vs EBRT and Nitrosourea for Anaplastic Astrocytoma and Mixed Anaplastic Oligoastrocytoma

• RTOG 0229: Phase II Trial of Neoadjuvant Therapy with Concurrent Chemotherapy and High Dose Radiotherapy Followed by Surgical Resection and Consolidative Therapy for Locally Advanced Non-Small Cell Lung Carcinoma

Successful CDRP Trials: Recruitment

• IMRT H&N Trial – PI: Patrick Maguire, MD– New Hanover Regional Medical Center

• Phase II Trial APBI for DCIS using MammoSite brachytherapy– PI: Oscar Streeter, MD– USC, Centinela Freeman: David Khan, MD

• Rapid City Trials:• PI: Daniel Petereit, MD• Surveys: general, cancer, navigation• IMRT / Tomotherapy Prostate Trial• HDR Prostate Trial• HDR Breast Trial• ATM Trial

Phase II Trial of Hyperfractionated IMRT with Concurrent Weekly Cisplatin for Stage III & IVa Head & Neck Cancer

• PI: Patrick D. Maguire, M.D.• New Hanover Radiation Oncology

• Designed & opened in community with IMRT planning advice from university

Breast Brachytherapy

Partial Breast Irradiation for DCIS Using MammoSite Brachytherapy: A

Phase II Trial • Oscar Streeter, Pamela Benitez, Frank Vicini et al.

• N =133 patients enrolled, Eligibility criteria: age > 45, unicentric DCIS, m size < 3 cm, negative margin 1mm

• 34 Gy in 10 fractions BID, 1 cm peripheral to the balloon surface

• 133 patients enrolled, MammoSite was placed in 117 patients, and 17 explanted – 25% not eligible for intracavitary method– < 5 mm skin bridge (5%), poor cavity conformance (5%),

positive margin (3%), final histology (1%), MD decision (1%)

Phase II Trial HDR Brachytherapy Stage I and II Breast Cancer: Rapid City PI Petereit

• Similar criteria as previous APBI RTOG trial• 34 Gy/10 Fxs

• Endpoints:• Evaluate the rate acute, late toxicities • Efficacy, local control, cosmesis

• 16 pts enrolled out of 100 (3 AIs)• Majority interstitial technique• 2 G3 toxicity: recurrent infection requiring drainage

• Mammosite technique• Mainly interstitial technique

Phase II Study HDR Brachytherapy Intermediate Risk Prostate Cancer – Rapid City PI Petereit

• Patient eligibility: intermediate, high-risk prostate cancer

• Androgen ablation: 6 to 12 months

• EBRT: 2.2 Gy X 16 over 15 treatment days, HDR 6.5 Gy X 3

• Endpoints:• Evaluate the rate acute, late toxicities

• Efficacy HDR boost

• 4 patients enrolled (0 AIs) out of 100

• No G3 toxicities

• Lower accrual because of tomotherapy trial

• HDR FX schedule recently changed from 6.5 x 3, to 9 Gy x 2 to increase accrual by eliminating need for hospitalization

TOMOTHERAPY PROSTATE TRIAL Rapid City PI Petereit

4.3

Š 50 PTS Š 50 PTS Š 50 PTS

Phase I/II Hypofractionation Trial

Multi-institutional Phase I/II trial (PI: Mark Ritter, MD, PhD)-Level I/II completed (2006 ASTRO abstract #19)-160 patients: No G3 toxicities Rapid City: 30 patients enrolled (2 AIs) minimal toxicities, no G3-Most rapidly accruing trial ever opened

Level I nearly completed in Rapid City, adding 20 patients

ATM MUTATIONS in Native Americans: Possible Association with Cancer and Radiotherapy Toxicities

• PI: Petereit, DG

• To determine the association between ATM heterozygosity and sensitivity to radiation

• Gene sequencing underway

• Amy Moser, PhD

• 20 American Indians, 39 non-Natives

American Indians Entered on Research Trials Rapid City CDRP Era

Official start of Program: June 2004– General Survey: 713– Patient navigation: 181– Cancer Survey: 24– ATM: 20– CDRP treatment trials: 6– Cooperative Group Trials: 6– TOTAL: 769 - 950 if navigated pts included

Number of AIs on clinical trials nationally: 7– AACR 2006, Washington, DC

CDRP Enrollment Clinical Trials

Centinela Freeman (PI: Steinberg, M)– 26 patients on clinical trials; 208* patients navigated

UPMC McKeesport (PI: Heron, D)– 20 patients on clinical trials; 34 on behavioral trial; 261* patients

navigated

Rapid City (PI: Petereit, D)– 769 patients on clinical trials (includes behavioral); 181* patients

navigated

Singing River (PI: Dennis, S)– 6 patients on clinical trials; 353* patients navigated– Complete recovery from setbacks from hurricane Katrina




• RTOG, ECOG, NSABP, NCCTG, GOG– CDRP trials: PI driven– Other: behavioral, molecular


Successful Recruitment Clinical Trials

Patient considerations– Patient preference: randomized trial often difficult (RTOG 9804), no

treatment or treatment not desired

– Convenience, effectiveness• HDR prostate, IMRT prostate, partial breast radiation

– Stage at presentation, co-morbidities, performance status

MD consideration– Most effective and current regimens

– B-39: surgeons preference Mammosite device

– RTOG 9804- Med Oncs prefer aromotase inhibitors– NCIC MA.20: regional nodal RT: RO preference

– Complexity of trial– RTOG 0229: difficulty in obtaining tissue from N2 nodes via

mediastinoscopy• RTOG 0412 allows for trans-esophageal biopsy


• Quality of life studies, accrual easier• Non-invasive

• Investigator ownership • RTOG 0245 study PI UPMC McKeesport

Special considerations– Disparate populations

• Phase II: limited institutional basis

• Often difficult commit randomized trial, eg RTOG 0232

– Unforeseen: Katrina! Singing River


• Good studies for common cancers– How does it “fit” into community standards

• Community-Based Participatory Research• Key to successfully enrolling AIs Western, SD

• Community trust is the critical issue!

• ATM study» Evidence of trust established AI community

Timeline IRB Approval 2003 - 2004A

AIR

B

Prot 6: Tomo Prostate

Prot 3: Community SurveyProt 4: Navigator

Prot 2/1: Breast Brachy - NAI

Prot 5: Tomo Bone

Prot 1/1: Prostate Brachy - NAI

Prot 3: Community Survey

Nat

.IR

B


Prot 4: NavigatorProt 5: Tomo Bone

Prot 1/1: Prostate Brachy - NAI


UW

IR

B


Prot 5: Tomo BoneProt 2/2: Breast Brachy

Prot 1/1: Prostate Brachy - NAIProt 1/2: Prostate Brachy



RC

RH

IR

BProt 1/1: Prostate Brachy - NAI

Prot 5: Tomo Bone

Prot 3: Community SurveyProt 4: Navigator

Prot 2/2: Breast Brachy

Prot 1/2: Prostate Brachy


Submitted

Approved withfinal letter

Ready to enroll after NCI appr.

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• RTOG, ECOG, NSABP, NCCTG, GOG– CDRP trials: PI driven– Other: behavioral, molecular


Considerations Future Clinical Trials

• “With precise, treatment delivery systems, cooperative groups need to think about hypofractionation rather than delivering a higher total dose over a longer period of time”– Michael Steinberg, MD, Centinela Freeman

• Patients are asking for more convenient, cost effective and equally effective treatments

Considerations Future Clinical Trials

• Presenting randomized study is difficult because patients want to choose their treatment

• Phase II trials might be a better option for these special populations- American Indians Western, SD, choice is often

mastectomy or brachytherapy, situation in Anchorage, Al, magnified by factor of 10

– Strong rationale for offering phase II trials limited institutional basis through cooperative group mechanism

• NCCTG proposal

Geographic Distance from The Cancer Center in Western, SD

Live 70 to 180 miles away (Median 140 miles)

Travel Distances Alaskan Natives

To'katakiya zanniyan omani pi ye/yo To'katakiya zanniyan omani pi ye/yo

Documents

Clinical Trials that Address Health Care Disparities Daniel G. Petereit, MD Department of Radiation Oncology University of Wisconsin Medical School University