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CLINICAL TRIALS - A PATHWAY TO A CURE
CanSurvive Monthly Support Group
February 19th, 2017
Anna Burton, BSN, RN
OBJECTIVES
• Be able to describe the phases of a clinical trial
• Be aware of the current clinical trials at UAB GYN
Oncology
Why we use phases
• Phases help define and describe the type of study.
• Important for supporting the licensing of a drug.
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Basic Information:
A protocol is a document describing the
rationale, materials, and methods for
conducting a research study.
A well designed protocol provides the clinical
research team instructions and directions
that are strongly supported by scientific
rationale for conducting the study
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Pre-clinical Trial
Purpose:
To identify a new drug or treatment that
could be suitable in humans.
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Phase 1 Clinical Trial
• Clinical Trials start at Phase 1:
• Focus is on safety and tolerability. Seeks safest dose,
bioavailability rather than efficacy.
• Usually single dose or increasing dose to discover the
maximum tolerated dose
• Could be first in humans
• Small number of participants (usually <50).
• 6-18 months to complete
• 40% of new drugs fail in Phase 1 trials
Phase 2 Clinical Trial
• Phase 2 trials are focused on determining the
efficacy of the drug in a larger number of patients
(perhaps several hundred) suffering from the
condition that the drug is intended to treat
• These trials may be performed globally and give
information on efficacy and allow for a further
estimation of safety in a larger population
• 6 months to 2-3 years to complete
• 62 % of the phase 1 drugs in phase 2 trials will fail.
Phase 3 Clinical Trials
• Assuming satisfactory results from phase 2 studies, the drug
will enter phase 3 clinical trials
• 2-4 years or longer to complete
• Usually randomized, double-blind; compares new treatment
to standard or control
• The trials would routinely involve several thousand patients
and compare the investigational drug with drugs that are
currently in use for the treatment of the target disease
(“comparators”)
• 40% of phase 2 drugs will fail in phase 3 studies.
• The results from these trials essentially form the basis of the
risk/benefit analysis that will be submitted to the regulatory
authorities
The protocol is complete!
• The endpoints are obtained, the data is analyzed
and the final report is prepared.
• The manuscript(s) is written and published.
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NDA: New Drug Application
• Submitted to FDA
• Summary of all work done to date, including:
• Data from IND
• Clinical Trial Results
• Additional data on preclinical, drug substance and product
manufacturing and animal studies
• Proposed product labeling
One NDA can have up to 15 sections and over 100,000 pages.
The review process can take up to 18 months
FDA Approval
• The Food and Drug Administration can grant
either regular or accelerated marketing
approval for oncology drugs.
• Regular approval is based on endpoints
demonstrating that the drug provides a clinical
benefit, such as longer life, enhanced quality
of life, or a favorable effect on an established
surrogate for longer or better life, such as
long-term complete responses
Phase 4 Clinical Trial
• These trials are often referred to as post-marketing
studies and they are performed after the medicine
has been approved
• These give a greater idea of long term risk and
benefit and may give indications as to how use can
be modified
• The trials may involve many thousands of patients
and go on for many years
• Such trials may assist in indicating other uses for the
medicine
So What Will Oncology Clinical Trials of Tomorrow
Look Like??
• Emphasis has begun to shift from large scale studies
of relatively unselected patients to smaller studies
selecting more narrowly targeted to molecularly
characterized populations.
• A more personalized or precision approach
• Advances in genomics and cancer biology over the
last decade have provided viable targets for cancer
treatment.
Smaller, More Precise Trials Ahead
• There is a rise in the number of trials that
incorporate molecular tumor testing prior to
treatment, with the selection made by the molecular
features of each individuals cancer.
• These “personalized” trials have the potential to
yield better outcomes by increasing the probability
of response with less toxicity.
• Clinical trials should get much smaller – fewer
participants are needed when therapeutic benefit is
larger.
2014 Targeted Therapy Approvals
• Accelerated approval to nivolumab (OPDIVO, Bristol-Myers Squibb
Company) BRAF + Melanoma
• Approved olaparib capsules (Lynparza, AstraZeneca Pharmaceuticals LP)
BRCA mutated Ovarian CA
• Approved lanreotide (Somatuline Depot Injection, Ipsen Pharma)
• Approved ramucirumab (Cyramza Injection, Eli Lilly and Company) EGFR
Inhibitor, Stomach CA
• Approved ruxolitinib (Jakafi, Incyte Corporation) JAK 2 inhibitor,
Polycythemia Vera
• Accelerated approval for blinatumomab (BLINCYTO, Amgen Inc.)
Philadelphia chromosome Neg R/R ALL
2014 Targeted Therapy Approvals
• Accelerated approval to pembrolizumab (KEYTRUDA, Merck Sharp &
Dohme Corp.) BRAF + Melanoma
• Approved idelalisib (Zydelig tablets, GileadSciences, Inc.) PI3K Kinase
Inhibitor, CLL
• Accelerated approval to belinostat (BELEODAQ, Spectrum
Pharmaceuticals, Inc.) HDAC Inhibitor, T-cell Lymphoma
• Accelerated approval to ceritinib (ZYKADIA, Novartis Pharmaceuticals
Corporation) ALK + NSCLC
• Accelerated approval to ibrutinib (IMBRUVICA, Pharmacyclics, Inc.) BTK
Inhibitor, CLL
• Accelerated approval to trametinib (Mekinist tablets, GlaxoSmithKline,
LLC) and dabrafenib (Tafinlar capsules, GlaxoSmithKline, LLC) BRAF +
Melanoma
Current UAB Research Studies for Ovarian Cancer
• Phase 1 Celsion – Neo Adjuvent Chemotherapy after biopsy (UAB1534)
• Phase 1B – Plexxicon Oral TKI + Weekly Taxol (UAB1571)
• Phase 2/3 OXiGENE – FOCUS – Chemotherapy + Avastin + vascular
disrupting agent OX3425 (UAB1647)
• Phase 3 Abbvie/GOG – Neo Adjuvant or Adjuvent Chemotherapy
PARP Inhibitor (Veliparib) (UAB1558)
• Phase 3 SOLO3 for BRCA+ -- Third line treatment with a Parp
Inhibitor (Olaparib) (UAB14109)
Questions