NcXHF

CLINICAL TRIALS AND GI MALIGNANCIES
seeking treatment that is tailored to their cancer, and they
may choose off-label agents as a result of such tests instead of
enrollment in a clinical trial. Furthermore, numerous clinical
trials are now selecting patients with specifıc, and often
rare, mutations. Accrual to these studies can be very
slow and expensive when an investigator has to screen 100
patients to enroll 3 in a disease where the actionable mutation
occurs in only 3%.
THE PERSONAL TOLL: THE PATIENT PERSPECTIVE
Access to and the availability of clinical trials are paramount
to patients with cancer. To what lengths would you go to save
your own life? What would it mean to be told all approved
medical treatment options have been exhausted for your type
of cancer? From the patient perspective, as much as one
would desire to labor under the assumption that “plan A”
treatment will cure your cancer, discussing “plan B” could
prove benefıcial before completion of primary treatment.
Initial treatment plans should include long-term strategies
for cancer management, regardless of stage at diagnosis. Indeed,
initial conversations with an oncologist should include
clinical trials, even if no trial is available for that patient at
that time. Concern about whether the prescribed treatments
will work easily overshadows any quoted statistics. Additionally,
effıcacy of current treatment regimens is a moot point to
the newly diagnosed unless it is 100%. (For example: if a
treatment has an 80% effıcacy rate, the patient will undoubtedly
ask what happens if he or she has a disease that is part of
the 20% failure rate.)
Knowledge about available clinical trials offers a sense of
preparedness that helps to fulfıll a basic human need: safety.
Physicians should not assume that patients will know what
clinical trial options exist for their disease and thus proactively
ask physicians about them if they are interested in
enrollment. Even if that was the case, discovering and profıciently
navigating clinical trial search engines proves diffıcult
under the best of circumstances. Discussing clinical trial options
with patients serves a dual purpose. First, it displays the
physician’s confıdence in clinical trials as a viable treatment
option, which serves to nourish the patient’s precarious
safety needs. Second, rapid and educated decision making is
often critical for patients diagnosed with aggressive and/or
rare cancers, and this requires profıciency in deciphering the
current active clinical trial library. Cross referencing data for
trial drugs also would be helpful to patients who want to explore
every treatment avenue. Access to clinical trials for patients
with any type of cancer—common or rare, primary or
recurrent—is vital. The words “you have cancer” are life altering.
Coupled with advanced staging or rarity, those words
are life threatening. Improved access to and availability of
clinical trials with promising drugs or treatment regimens do
more than just satisfy enrollment numbers, they offer hope.
And hope is essential for patients with cancer.
PROPOSALS FOR IMPROVEMENT: THE PATIENT
ADVOCATE PERSPECTIVE
Most patients with cancer are diagnosed in a community setting.
It is imperative to create a culture of research in which
an oncologist is expected to discuss trials with patients, enroll
or refer them when appropriate, and do so with minimum
disruption to their practice while taking pride (and perhaps
even a marketing advantage) in participating in a larger research
effort. 14 Establishing an infrastructure that support
trials conducted in the community is essential.
Clinical researchers need to design trials for real-world patients;
trials that match the demographics of the disease and
trials that can be conducted in a community setting. Eligibility
criteria designed for phase I trials of cytotoxic chemotherapy
should be simplifıed and loosened for phase II and III
trials, especially for treatments that do not include cytotoxic
chemotherapy. Published literature of rare cancers is largely
based on retrospective single institution studies or database
reviews. Allowing enrollment of patients with select rare diseases
into common cancer trials would allow otherwise ineligible
patients to have access to treatment and would provide
additional prospective data for rare diseases. This methodology
has already been accepted by the Gynecologic Oncology
Group (GOG); patients with primary peritoneal cancers are
allowed to enroll in ovarian cancer trials. GI oncologists have
agreed to include gall bladder cancers in trials for cholangiocarcinomas.
Therefore, why not include appendiceal and
small intestinal adenocarcinomas in metastatic colorectal trials
or ampullary tumors in pancreatic cancer trials? Studies
can be powered for the primary endpoint of the more common
tumor (if necessary). We do not pretend that appendiceal
adenocarcinoma is the same as colon adenocarcinoma,
yet, in the absence of data, we tend the treat them the same off
protocol. Therefore why not gather some data on protocol?
Dramatic improvements in small subsets of molecularly
defıned lung cancers using targeted therapies have demonstrated
the feasibility of this approach. However, will we ever
be able to conduct a randomized trial in the 10% to 15% of
gall bladder cancers that are HER2/neu-positive? 15 The proliferation
of gene sequencing and other assays intended to
detect specifıc molecular vulnerabilities in cancer have resulted
in too many “one-off” experiments. That is, a nonprotocol
patient who gets a test result suggesting that a drug
might be useful, based on either preclinical experiments or
clinical experience in another disease, might then respond or
not respond to that drug, but that data is never (or seldom
ever) added to a database. The pharmaceutical industry and
the NCI have created basket trials that are agnostic of tumor
site of origin and accrue to treatment arms based on molecularly
defıned targets. These basket studies are methods of
discovery and not likely paths to U.S. Food and Drug Administration
approval of a drug for a specifıc target.
Disease-specifıc, molecularly targeted therapies can only
occur in more common cancers. BATTLE and ISPY trials for
lung and breast cancer, respectively, offer disease-specifıc options
in targeted therapy design that could be adopted in
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK 41