What Are Clinical Trials?

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Cancer Clinical Trials
The Basics
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What Are Cancer Clinical Trials?

• Research studies involving people
• Try to answer scientific questions and find
  better ways to prevent, diagnose, or treat cancer

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Why Are Cancer Clinical Trials Important?

• Cancer affects all of us
• Each year in the U.S.A
• More than half a million people are expected to
  die of cancer more than 1,500 people a day
• 1 of 4 deaths is from cancer
• More than 1 million new cancer cases are expected
  to be diagnosed

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Why Are Cancer Clinical Trials Important?

• Clinical trials translate results of basic
  scientific research into better ways to prevent,
  diagnose, or treat cancer

• The more people that take part, the faster we
  can
• Answer critical research questions
• Find better treatments and ways to prevent cancer

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Do Many People Participate in Cancer Clinical
Trials?

• Only 3 percent of U.S. adults with cancer
  participate in clinical trials

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Types of Cancer Clinical Trials

• Treatment trials
• Prevention trials
• Early-detection trials/screening trials
• Diagnostic trials
• Quality-of-life studies/supportive care studies

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Clinical Trial Phases

• Phase 1 trials
• How does the agent affect the human body?
• What dosage is safe?

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Clinical Trial Phases

• Phase 2 trials
• Does the agent or intervention have an effect on
  the cancer?

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Clinical Trial Phases

• Phase 3 trials
• Is the new agent or intervention (or new use of a
  treatment) better than the standard?
• Participants have an equal chance to be assigned
  to one of two or more groups

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Randomized Trials

• Participants have an equal chance to be assigned
  to one of two or more groups
• One gets the most widely accepted treatment
  (standard treatment)
• The other gets the new treatment being tested,
  which researchers hope and have reason to believe
  will be better than standard treatment

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Randomization
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Why Is Randomization Important?

• So all groups are as alike as possible
• Provides the best way to prove the effectiveness
  of a new agent or intervention

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Cancer Treatment Trials

• What new treatments can help people who have
  cancer?
• What is the most effective treatment for people
  who have cancer?

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Cancer Treatment Trials

• Placebos are almost never used
• Placebos are used only when no standard treatment
  exists
• Patients are told of this possibility before
  deciding to take part

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Cancer Prevention Trials

• Evaluate the effectiveness of ways to reduce the
  risk of cancer
• Enroll healthy people at high risk for developing
  cancer

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Cancer Prevention Trials

• Action studies
• (doing something)
• Agent studies
• (taking something)also called
  chemoprevention studies

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Chemoprevention Trials

• Phase 3 chemoprevention trials compare a
  promising new agent with either a
• Standard agent
• Placebo

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Clinical Trial Protocol

• A recipe or blueprint
• Strict scientific guidelines
• Purpose of study
• How many people will participate
• Who is eligible to participate
• How the study will be carried out
• What information will be gathered about
  participants
• Endpoints

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Benefits of Participation

• Possible benefits
• Patients will receive, at a minimum, the best
  standard treatment
• If the new treatment or intervention is proven to
  work, patients may be among the first to benefit
• Patients have a chance to help others and improve
  cancer care

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Risks of Participation

• Possible risks
• New treatments or interventions under study are
  not always better than, or even as good as,
  standard care
• Even if a new treatment has benefits, it may not
  work for every patient
• Health insurance and managed care providers do
  not always cover clinical trials

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Patient Protection

• There have, unfortunately, been past abuses in
  patient protection
• Federal regulations ensure that people are told
  about the benefits, risks,
  and purpose of research before they agree to
  participate

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How Are Patients Rights Protected?

• Informed consent
• Scientific review
• Institutional review boards (IRBs)
• Data safety and monitoring boards

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How Are Patients Rights Protected?

• Informed consent
• Purpose
• Procedures
• Risks and potential benefits
• Individual rights

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How Are Patients Rights Protected?

• Scientific review
• Institutional review boards (IRBs) are required
  by Federal law for trials that are
• Federally funded
• Subject to FDA regulation

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How Are Patients Rights Protected?

• Data and safety monitoring boards
• Ensure that risks are minimized
• Ensure data integrity
• Stop a trial if safety concerns arise or
  objectives have been met

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Why Do So Few Cancer Patients Participate in
Clinical Trials?

• Sometimes patients
• Dont know about clinical trials
• Dont have access to trials
• May be afraid or suspicious of research
• Cant afford to participate
• May not want to go against physicians wishes

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Why Do So Few Cancer Patients Participate in
Clinical Trials?

• Doctors might
• Lack awareness of appropriate clinical trials
• Be unwilling to lose control of a persons care
• Believe that standard therapy is best
• Be concerned that clinical trials add
  administrative burdens

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NCI Information Resources

• NCI Web sitewww.cancer.gov
• Cancer Information Service
• 1-800-4-CANCER
• TTY- 1-800-332-8615
• www.cancer.gov/cis

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IOWA ONCOLOGY RESEARCH ASSOCIATION
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Iowa Oncology Research Association

• Established in 1977 as CGOP
• Became a member of NCCTG in 1978
• Designated a CCOP in 1983

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Affiliate Sites

• Mason City
• Ottumwa
• Ames

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Clinical Trials

• Chemotherapy
• Radiation Therapy
• Immunotherapy
• Surgery
• Correlative Studies
• Cancer Control
• Cancer Prevention

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Cooperative Group Memberships

• North Central Cancer Treatment Group
• Eastern Cooperative Oncology Group
• National Surgical Adjuvant Breast Bowel
  Project
• Southwestern Oncology Group

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Protocol Development

• Protocol concept developed by cooperative group
  committees
• Often distributed to participating investigators,
  CRAs, nurses for peer review
• Submitted to NCI for review

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Implementation Of Study

• Distributed to affiliate sites via weekly emails
• Optional participation
• Factors affecting local participation
• Eligibility criteria
• Competing studies
• Test requirements
• Local IRB review

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Patient Recruitment

• Treatment and control studies Oncology patients
  referred by local physicians
• to IORA
• Cancer prevention studies Various recruitment
  efforts utilized

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Drug Procurement

• Drugs ordered from sponsoring cooperative group
• or
• Drugs ordered from Pharmaceutical Management
  Branch (PMB) of NCI

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Randomization / Registration

• Fax
• Online
• All randoms / registrations require at minimum a
  completion of eligibility criteria checklist

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Quality Assurance

• Pathology review
• Radiation therapy review
• Surgery review

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Quality AssuranceContinued

• Data Safety Monitoring Policies
• Data Safety Monitoring Board (DSMB)
• Site Audits

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Adverse Event Reporting

• Common Toxicity Criteria (CTC)
• Adverse Event Expedited Reporting System (AdEERS)

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BRAIN TUMORS
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RECURRENT BRAIN TUMORS

• NCCTG N0272 Phase II Trial of STI571 in
  Treatment of Recurrent Oligodendroglioma Mixed
  Oligoastrocytoma
• NCCTG N0572 Phase I/II Trial of Sorafenib
  CCI-779 in Recurrent Glioblastoma
• NCCTG N0779 Phase II Study of Vorinostat (SAHA)
  in Combination with Bortezomib (PS-341) in
  Patients with Recurrent Glioblastoma Multiforme

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METASTATIC BRAIN TUMORS

• NCCTG N0574 Phase III Randomized Trial of the
  Role of Whole Brain Radiation Therapy in Addition
  to Radiosurgery in Patients with 1-3 Cerebral
  Metastases

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BREAST CANCER
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ADJUVANT TREATMENT

• CALGB C40101 Phase III, Randomized, 2 x 2
  Factorial Study of Cyclophosphamide Doxorubicin
  (CA x 4 Cycles) vs Paclitaxel (4 Cycles) as
  Adjuvant Therapy for Breast Cancer in Women with
  0-3 Positive Axillary Nodes
• ECOG E5103 A Double-Blind, Phase III Trial of
  Doxorubicin Cyclophosphamide Followed by
  Paclitaxel with Bevacizumab or Placebo in
  Patients with Lymph Node Positive High-Risk
  Lymph Node Negative Breast Cancer

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ADJUVANT TREATMENT

• ECOG PACCT-1 Program for the Assessment of
  Clinical Cancer Tests Trial Assigning
  Individualized Options for Treatment
• SWOG S0221 Phase III Trial of Continuous Schedule
  of AC G vs Every 2 Week Schedule AC, Followed
  by Paclitaxel Given Either Every 2 Weeks or
  Weekly for 12 Weeks as Post-Operative Adjuvant
  Treatment in High Risk Node Negative or Node
  Positive Breast Cancer

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ER / PR POSITIVE

• NSABP B-42 A Clinical Trial to Determine the
  Efficacy of 5 Years of Letrozole Compared to
  Placebo in Patients Completing 5 Years of
  Hormonal Therapy Consisting of an AI or Tamoxifen
  Followed by an AI in Prolonging Disease-Free
  Survival in Postmenopausal Women with Hormone
  Receptor Positive Cancer
• CALGB C40503 Endocrine Therapy in Combination
  with Anti-VEGF Therapy Randomized,
  Double-Blind, Placebo-Controlled Endocrine
  Therapy Plus Bevacizumab for Women with Hormone
  Receptor Positive Advanced Breast Cancer

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WHOLE VS PARTIAL BREAST IRRADIATION

• NSABP B-39 Randomized Phase III Study of
  Conventional WBI vs PBI for Women with Stage 0, I
  or II Breast Cancer

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HER2 Positive

• NCCTG N063D ALTTO Adjuvant Lapatinib and/or
  Trastuzumab Treatment Optimization Study
  Randomized, Open-Label, Phase III Study of
  Adjuvant Lapatinib, Trastuzumab, Their Sequence
  Their Combination in Patients with HER2 Positive
  Primary Breast Cancer

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METASTATIC / RECURRENT

• ECOG E1104 Phase I/II Study of SAHA in
  Combination with Herceptin in Patients with
  Advanced Metastatic and/or Local Chest Wall
  Recurrent HER2 Amplified Breast Cancer
• ECOG E1105 Randomized Phase III Double-Blind,
  Placebo-Controlled Trial of First-Line Chemo
  Trastuzumab With or Without Bevacizumab for
  Patients with HER2 Overexpressing Metastatic
  Breast Cancer

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METASTATIC / RECURRENT

• NCCTG N0539 Phase II Trial of Fulvestrant
  Bevacizumab in Patients with Metastatic Breast
  Cancer Previously Treated with an Aromatase
  Inhibitor
• SWOG S0500 Randomized Phase III Trial to Test the
  Strategy of Changing Therapy vs Maintaining
  Therapy for Metastatic Breast Cancer Patients Who
  Have Elevated Circulating Tumor Cell Levels at
  First Follow-up Assessment

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OVARIAN FUNCTION SUPPRESSION

• IBCSG 2402 Ovarian Function Suppression
  Exemestane as Adjuvant Treatment for
  Premenopausal Women with Endocrine Responsive
  Breast Cancer
• CALGB C40302 Endocrine Therapy With or Without
  Inhibition of EGF HER2 Growth Factor Receptors
  Randomized, Double-Blind, Placebo-Controlled
  Phase III Trial of Fulvestrant With or Without
  Lapatinib for Post-Menopausal Women With
  Hormone-Receptor Positive Advanced Breast Cancer

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