The University of Arizona Cancer Prevention Clinical Trials Network (UA CP-CTNet) is a major program funded by the National Cancer Institute, Division of Cancer Prevention (https://prevention.cancer.gov/major-programs/cancer-prevention-clinical-trials-network) to perform early phase clinical trials to evaluate the clinical activity and biologic effects of putative preventive agents and to determine clinically relevant correlates in order to identify agents with good safety profiles and preliminary efficacy. Scientific and clinical evidence generated from these early phase cancer prevention clinical trials will contribute significantly to the clinical development of safe and effective agents for cancer prevention.

The University of Arizona Cancer Center received an $8.6 million grant from the National Cancer Institute for the UA Cancer Prevention Clinical Trials Network, one of only five such networks funded by the NCI.

https://cancercenter.arizona.edu/news/2019/10/ua-cancer-center-receives-86m-grant-lead-one-three-nci-clinical-trials-networks

The UA CP-CTNet is an extension of the UA Early Phase Chemoprevention Consortium which has been funded continuously by NCI since 2003 to conduct early-phase clinical trials of chemopreventive agents.

Since its inception in 2003, the NCI-funded UA Chemoprevention Consortium has conducted 17 early phase cancer prevention clinical trials encompassing evaluation of repurposed drugs, well-characterized nutraceuticals, alternative dosing schedules, regional/topical drug delivery, and novel vaccines.  Target organs include lung and upper aerodigestive cancers, HPV-associated cancers, breast prostate, skin, cervical and esophageal cancers. 

Advances in molecular understanding of the process of carcinogenesis have led to the study of an increasing number of agents to intercept the early phases of cancer development, including the recent interest in immunoprevention.  The overall objective of the UA CP-CTNet is to perform early phase clinical trials to evaluate the clinical activity and biologic effects of putative preventive agents, and to determine clinically relevant correlates in order to identify agents with good safety profiles and preliminary efficacy for definitive Phase III trials.

The UA CP-CTNet consists of the University of Arizona (UA) as the Lead Academic Organization (LAO) and 12 Affiliated Organizations (AOs) that work together to perform early phase cancer prevention clinical trials. This network is led by Drs. Julie Bauman https://cancercenter.arizona.edu/person/julie-e-bauman-md-mph and Sherry Chow https://cancercenter.arizona.edu/person/hsiao-hui-sherry-chow-phd and is composed of a team of physicians from diverse specialties, statisticians, clinical staff, data managers, pathologists, translational scientists, and other personnel with extensive experience in early phase (phase 0, 1 or 2) clinical trials of cancer preventive agents and in translational research in various organ sites.

The 12 Affiliate Organizations are:

British Columbia Cancer Agency

Emory University

George Mason University

Johns Hopkins University

Moffitt Cancer Center

Norton Thoracic Institute

Oregon Health & Science University

Stanford University

University of California San Diego

University of Minnesota

University of North Carolina

University of Southern California

Investigators in the UA CP-CTNet are organized into five organ system groups to facilitate scientific interactions among investigators at the LAO and AOs with shared interests. Core personnel provide oversight and coordination of development of study concepts, protocol development, participant accrual, study conduct, trial endpoint evaluation, and study manuscripts/abstracts preparation and submission. The collaboration in UA CP-CTNet cover a wide range of transdisciplinary expertise that offers the opportunities of developing agents for melanoma and non-melanoma skin cancer prevention, lung and upper aerodigestive cancer prevention, breast and gynecologic cancer prevention, prostate and urologic cancer prevention, and gastrointestinal cancer prevention.

The overall objective of University of Arizona Cancer Prevention Clinical Trials Network (UA CP-CTNet) is to perform early phase clinical trials to evaluate the clinical activity and biologic effects of putative preventive agents and to determine clinically relevant correlates to identify agents with a good safety profile and preliminary efficacy for definitive trials.

Aim One: Efficiently design and conduct Phase 0/I/II clinical trials to assess the cancer preventive potential of repurposed drugs that affect multiple chronic diseases, well-characterized nutraceutical agents, regional/topical drug delivery, and immune modulators, rigorously identified from translational research, epidemiological studies, and/or clinical research.

Aim Two: Characterize the clinical activity and biological effects of putative cancer preventive agents on their defined molecular/biochemical targets, the immune surveillance network, surrogate endpoints associated with carcinogenesis, and other biological effect markers identified in preclinical studies.

Aim Three: Develop further scientific insights into the mechanisms of cancer prevention by the agents studied and to develop novel potential markers as determinants of response and for selecting subpopulations who may differentially benefit from the studied agent.

Through the conduct of rigorously designed early phase cancer prevention clinical trials, the UA CP-CTNet will determine the clinical activity and biological effects of potential preventive agents. The research findings will further scientific insights into the mechanisms of cancer prevention and develop novel potential biomarkers as determinants of response. Scientific and clinical evidence generated from these early phase cancer prevention clinical trials will contribute significantly to the decision for advancing a candidate agent for further clinical development for cancer prevention.

The collaboration in UA CP-CTNet cover a wide range of transdisciplinary expertise that offer the opportunities of developing agents for:

  • Melanoma and Non-Melanoma Skin Cancer Prevention
  • Lung and Upper Aerodigestive Cancer Prevention,
  • Breast and Gynecologic Cancer Prevention,
  • Prostate and Urologic Cancer Prevention
  • Gastrointestinal Cancer Prevention.

Currently, there are three NCI-supported CP-CTNet trials:

For More information on the UA CP-CTNET please contact the University of Arizona Cancer Prevention Clinical Trials Network at 520-321-7444 OR UACC-CPRE@UACC.arizona.edu

 

 

The University of Arizona Cancer Prevention Clinical Trials Network (UA CP-CTNet) is conducting an extended follow-up study with study participants of the original “HPV Vaccine Delayed Booster Trial” to determine if a single dose of Gardasil 9 with a delayed booster injection at 24 months show a stable response after the booster.

The National Cancer Institute sponsors this study, which is conducted under the direction of UA CP-CTNet Principal Investigators, H-H Sherry Chow, PhD and Julie Bauman, MD, MPH, and Protocol Principal Investigator, Yi Zeng, MD, PhD.

This study is being done to answer the following questions:

Can the delayed booster injection of Gardasil 9 generate stable and persistent immune response to protect against HPV infection?

Can we detect HPV virus and antibodies in urine?

Background for conducting this trial:

Human papillomavirus (HPV) infection is the most prevalent precursor for cervical cancer and is associated with the development of several genital cancers as well as oral cancers in both

women and men. The available HPV vaccines are very effective in preventing HPV-attributed cancers. A 2-injection vaccine schedule with the second injection given 6-12 months after the first injection is recommended for children ages 9 through 14 years.

Analysis of prior clinical trials data suggests that a single injection of HPV vaccine may give a sufficiently strong immunogenic response to elicit a degree of protection against HPV- associated cancers. These data raise interesting prospects for potential efficacy of a single injection of vaccine and raise hopes for substantial cost savings and logistical simplifications for HPV vaccine implementation across the globe.

The original “HPV Vaccine Delayed Booster Trial” was conducted to determine if a single dose of Gardasil 9, the only HPV vaccine available in the United States can generate stable and persistent immune response in preteen girls and boys. The analysis of the immune response in the original “HPV Vaccine Delayed Booster Trial” is ongoing. The preliminary findings suggest that the response to the two most common types of HPV are persistently detected for up to 24 months after a single dose of Gardasil 9. As of 2019, there are ongoing supply constraints/shortages of HPV vaccines globally. Our preliminary findings contributed to the upcoming recommendation from the World Health Organization to consider delaying the booster dose in young girls to ensure maximum coverage of age-appropriate recipients.

The original “HPV vaccine delayed booster trial” will allow for determination of the stability and persistence of antibody response after a single dose of the HPV vaccine over 24 months. The follow-up trial will help determine if the 24-month delayed booster of the vaccine will generate a stable and persistent immunologic response. A stable and persistent immunogenicity infers lasting protection against HPV infection. These studies are expected to inform future HPV vaccination policy to improve vaccine uptake and implementation to prevent HPV-attributed cancers and diseases.

For questions, contact the University of Arizona Cancer Prevention Clinical Trials Network at 520-321-7444 or UACC-CPRE@UACC.arizona.edu.

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Karen Hastings, MD, PhD

The University of Arizona Cancer Prevention Clinical Trials Network (UA CP-CTNet) is conducting a study to develop biomarkers that can be used in early phase melanoma prevention trials.

Melanoma is the most serious form of skin cancer. Sun exposure remains the major environmental risk factor for developing melanoma. The incidence of melanoma continues to increase despite public health initiatives that have promoted sun protection. For this reason, it is important to pursue investigation of new approaches to melanoma prevention such as chemoprevention.

Previous studies suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) such as sulindac may reduce the risk of melanoma, although there are some inconsistencies in the data. In collaboration with Stanford University, University of Arizona conducted a trial of sulindac to evaluate its use in melanoma prevention in individuals with multiple atypical nevi (abnormal moles). The study showed that sulindac was distributed to the moles and also demonstrated some biological activities in the nevi, supporting continued clinical development of sulindac for melanoma prevention. In planning for a follow-up sulindac trial, the study team identified the critical need for further development of biomarkers for early phase melanoma prevention trials. This proposed biomarker development research is critical to the design of a follow-up sulindac trial to provide more compelling evidence to qualify sulindac for future trials.

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Clara Curiel, MD

The specific aims of this study are to develop molecular signatures to distinguish the stages of melanoma progression and to determine the effects of sulindac intervention on gene expression profile by analyzing tissue samples from the previous sulindac trial.

This study is sponsored by the National Cancer Institute and conducted under the direction of UA CP-CTNet Principal Investigators H-H Sherry Chow, PhD and Julie Bauman, MD, MPH. The study investigators include Karen Hastings, MD, PhD, Clara Curiel, MD, and Bonnie LaFleur, PhD. Kenneth Buetow, PhD will provide bioinformatics expertise.

For Questions, contact the University of Arizona Cancer Prevention Clinical Trials Network at 520-321-7444 OR UACC-CPRE@UACC.arizona.edu