T Phase I Retreat Addresses Phenomenal Program Growth and Future Directions

Phase I Retreat Addresses Phenomenal Program Growth and Future Directions
second annual retreat of the Phase I
T10thheWorking
Group and Program held Nov.
reverberated with issues surrounding
the program’s remarkable growth since its
inception in July 2004, marked by both
extraordinary achievements and the
growing pains that inevitably accompany
rapid progress.
“There is a tremendous demand for new
drugs, since many of the 65,000 patients seen
last year at M. D. Anderson had metastatic
disease that is not curable or very treatable,”
remarked Razelle Kurzrock, M.D., director of
the Phase I Program. “The patient comes
first,” said Dr. Kurzrock. “There has been a
dramatic increase in patient volume in the
program’s Clinical Center for Targeted
Therapies. Yet we are inundated by so many
referrals that we can’t meet the demand for
the number of patients who want to be seen.”
Over the past year, the Phase I Program also
set a precedent for offering more clinical trials
open to special populations. This included
elderly and pediatric patients as well as
patients with renal or hepatic insufficiency or
CNS metastases.
To keep up with requests to try new
agents, Dr. Kurzrock noted that “we need to
increase the number of high-impact, broad
Phase I trials to about 50 while keeping the
emphasis on quality and moving forward in
the scientific arena. We also need to
strengthen and expand the program’s
infrastructure of faculty, research nurses,
and study coordinators. These advances
will enable us to serve patients well, test the
highest priority compounds, and establish
the next stage of scientific direction—
individualized therapy.”
In his presentation, David Stewart, M.D.
addressed the advantages and disadvantages
of conducting NCI-sponsored studies.
He noted that while they tend to be under
funded and the approval process is
cumbersome, the NCI offers a huge number
of molecules, additional generous funding
mechanisms such as R21 and Translational
Research Initiative grants, and a pioneering
initiative to combine investigational agents.
Overall, participants were in agreement to
increase the number of NCI-sponsored
studies—a top priority of division head
Waun Ki Hong, M.D. as well.
NOVEL DRUGS IN THE PIPELINE
Roy Herbst, M.D., Ph.D. introduced the
summary of the breakout session on novel
drugs in the pipeline by asking, “How are we
getting drugs for Phase I studies? How can
we do better?” Francis Giles, M.D. answered,
“The institution can’t do any better to
get more drugs. The drug pipeline at
M. D. Anderson is excessively and gorgeously
full. We have access to any drug any time we
want. But we need to get our own logistics
in order. We need better implementation.
We need to put the brakes on the
Why M. D. Anderson?
• We lead the way nationally in National Cancer Institute grant award dollars, receiving about $107 million annually.
• We have ten Specialized Programs of Research Excellence (SPORE) awards from the National Institutes of Health,
more than any other institution in the country.
• We see about 65,000 cancer patients per year.
bureaucracy. Now that we have plenty of
trials, the next step is to establish a biologic
rationale for putting patients in the studies.”
TRANSLATIONAL RESEARCH
The translational research breakout group
led by Dr. Herbst and William Bornmann,
Ph.D. called for more interaction between
groups such as the collaboration between
Experimental Diagnostic Imaging and
Experimental Therapeutics to foster
molecular targeting, along with increased
institutional support to launch investigators
looking for partners, to bring more molecules
to the clinic. They suggested creating
mechanism-driven task forces that are
based on common objectives, such as an
anti-angiogenesis task force, that extend
beyond division and department boundaries.
Drs. Bornmann and Herbst reminded participants about the organic compound synthesis
laboratory, where compounds can be made
and labeled here at M. D. Anderson.
CHALLENGES FOR CONDUCTING
CLINICAL RESEARCH
A challenge that surfaced repeatedly throughout the retreat was the rapidly
escalating regulatory burden, which affects
everything from the number of trials a
research nurse can coordinate to the ability to
enroll a patient before it is too late in his or
her disease progression. The irony is that this
regulatory increase is occurring despite the
documented safety of Phase I studies and the
markedly lower toxicity of the new targeted
molecular therapies compared with classic
chemotherapy. “Phase I trials are enormously
safe,” Dr. Kurzrock commented. “The NCI
documented that there was less than a
continued on page 4
Lymphomas Respond to
Interleukin-6 Targeted Therapy
with Castleman’s disease and
Pearlyatients
mantle cell lymphoma are showing
evidence of response to CNTO 328, a
Dr. Kurzrock also expects to see future trials
of CNTO 328 in solid tumors, since
interleukin-6, an inflammatory cytokine,
has been implicated in the development
of many other tumors as well.
monoclonal antibody that targets
CDK Inhibitor Offers Significant
interleukin-6, without significant
Anti-Tumor Activity
toxicity. Two of the first three
ali Papadimitrakopoulou, M.D., associate
patients in this trial have
professor, Thoracic/Head and Neck
responded so far to CNTO 328,
Medical Oncology, is principal investigator
noted the trial’s principal investiof a first-in-humans Phase I study of
gator, Razelle Kurzrock, M.D. For
RO4584820, a novel and selective cyclin
example, a middle-aged woman
Razelle Kurzrock, M.D. with Castleman’s disease, a rare
dependent kinase inhibitor (mainly CDK1,
CDK2, and CDK4), for patients with solid
and difficult-to-treat lymphoid disorder,
tumors. CDKs regulate cell cycle progression
experienced relief from her presenting sympby phosphorylation-mediated inactivation of
toms of fever and rash within 24 hours of
various tumor suppressor proteins (e.g., the
therapy with CNTO 328. Her PET scans
retinoblastoma gene product RB). This agent
showed normalization after about three
has exhibited significant tumor growth inhibimonths of treatment. After failing other
tion and apoptosis induction in preclinical
treatment, an elderly man with mantle cell
trials. The primary objectives of this study are
lymphoma exhibited a marked decrease in
to determine the maximum tolerated dose
tumor metabolic activity within the initial
(MTD) and the recommended Phase II dose
eight weeks of therapy with CNTO 328 and
level. Secondary objectives are to determine
continues to do well.
the drug’s safety and tolerability as well as its
“CNTO 328 targets tumor cells without
pharmacokinetics, phamacodynamics
harming healthy tissue,” Dr. Kurzrock noted.
(inhibition of retinoblastoma phosphoryla“This is true targeted therapy developed on
tion), and pharmacogenomic profile.
a rational, hypothesis-driven basis.”
“The orderly progression of the cells
Department of Lymphoma/Myeloma chair
through the cell cycle in normal cells is assured
Larry Kwak, M.D., Ph.D., and assistant
by the function of several checkpoints, but
professor Luis Fayad, M.D, who are treating
cancerous cells do not have functional checkpatients enrolled in the study, are also
points. Because the dysregulated activity of
excited about this drug’s prospects. “The
CDKs plays a direct role in overcoming the
highly favorable response of patients with
normal checkpoint function, the CDKs have
Castleman’s disease could be expected
been considered the prime molecular targets
because interleukin-6 is centrally involved in
for the therapeutic growth control of cancer. A
the pathogenesis of Castleman’s disease and
distinct advantage of this drug is that its antimyeloma, said Dr. Kwak. “That’s what
tumor activity is unaffected by the schedule
makes CNTO 328 a truly targeted therapy.”
employed, therefore making it amenable to
This multi-site, Phase I study
combination with other drugs,” noted Dr.
sponsored by Centocor is actively
Papadimitrakopoulou. “We selected a dosage
recruiting patients with non-Hodgkin’s
schedule that will best accommodate combinB-cell lymphoma, multiple myeloma, or
ing it with other drug regimens.” Weekly
Castleman’s disease. Study candidates
intravenous doses of the drug will be adminismust be at least 18 years old, have
tered on a three-week treatment cycle basis.
measurable disease without metastases to
Enrollment in this study of adults with
the CNS, and have the ability to visit
measurable, locally advanced or
M. D. Anderson every week and receive
metastatic solid tumors is
drug infusions every other week.
underway. Patients are not
Another advantage of this drug is
eligible if they have taken a
its combinability with other drugs in
CDK inhibitor or inducer or if
future clinical trials to maximize response
they are currently taking a
potential. “Because there is no
strong inhibitor of CYP3A4
overlapping toxicity with other drugs,
such as ketoconazole. These
CNTO 328 can be easily combined
with other treatments,” said Dr. Fayad.
Vali Papadimitrakopoulou, M.D. drugs would interfere with
V
precise assessment of the MTD. Because
RO4584820 may lower blood pressure
significantly, patients with severe congestive
heart failure, cerebrovascular disease, or
cardiovascular disease are excluded, as are
patients who take antihypertensive drugs.
A New Happy Ending to
Arsenic and Old Lace?
ften called the poison of kings and king
O
of poisons, arsenic has been used to treat
cancer for more than 2,400 years. Its inorganic form has been associated with severe
liver toxicity and lung and skin cancer;
however, arsenic trioxide is FDA-approved
for the treatment of acute promyelocytic
leukemia. ZIO-101, a novel organic arsenic
formulation, may be safer and have greater
cell penetration than its predecessor.
Sponsored by Ziopharm, a Phase I clinical
trial of ZIO-101 in advanced
solid tumors aims to determine
its safety and the maximum
tolerated dose, pharmacokinetic profile, and anti-tumor
effects. Adults and children of
any age may be eligible to
Luis Camacho, M.D. participate in this study, but
must have measurable cancer lesions.
Luis Camacho, M.D., M.P.H., principal
investigator, noted that although it is too
early to see signs of response to the drug,
the first patient enrolled in the study (a
patient with renal cell cancer) not only
remained stable, but exhibited the
complete disappearance of two small brain
tumors. “The main concern is cardiac and
hematological toxicity, but we are not
seeing many side effects so far,” he said.
Because previous experience with arsenic
has resulted in prolongation of heart
conduction times and cardiac arrhythmias,
participants in this trial will undergo
outpatient cardiac monitoring before and
after each intravenous dose.
Although the mechanism of action
of ZIO-101 is not well understood, it is
believed to induce apoptosis and cell
cycle arrest in solid tumors whereas the
mechanism in hematologic malignancies is
more likely through terminal differentiation.
“This is also a differentiating agent,” said
Dr. Camacho. “The theory is that ZIO-101
takes abnormal cells and differentiates them
to become normal cells.” He noted that it is
too soon to ascertain future prospects for
combining ZIO-101 with other drugs.
CTRC RISES TO CHALLENGE OF MONITORING PHASE I PATIENTS ON COMPLEX REGIMENS
espite the increasing complexity of Phase I studies, the
Dstrives
Clinical and Translational Research Center (CTRC)
to provide a nearly around-the-clock, optimal
environment for the treatment of patients on Phase I clinical
trials, sampling for pharmacokinetics, and EKG monitoring
for cardiac side effects—all while providing outstanding
patient care.
The CTRC’s Steering Committee gives priority to selecting
early phase investigational drug protocols that could not be
conducted in a standard clinical unit because of their intensity,
complexity, or stringent time requirements, according to
Daniel Karp, M.D., the center’s medical director. In recent
years, the sheer number of events monitored per study has been rising
The number of
steadily. “In one treatment cycle
for one patient, we may have
patient visits to the CTRC
more than 100 auditable events
has risen dramatically, with
or checkpoints. In some proto1,000 visits in August alone and
cols, we are required to collect
close to 250 experimental treatments blood samples every 15 minutes.
administered per month.
It’s not unusual to get ten blood
samples per day from a single
Daniel Karp, M.D.
patient,” said Dr. Karp. “We’ve also
seen a sharp rise in cardiac event
monitoring such as the Q-T interval.
One drug study requires an EKG every few minutes.”
The number of patient visits to the CTRC has also risen
dramatically, with 1,000 visits in August alone and close to
250 experimental treatments administered per month. To help
keep track of patient progress on the trials, clinical research
program coordinator Jeffrey Rogers is developing an electronic
project management scheme using protocol icon graphics.
To successfully monitor about 25 to 35 ongoing intensive
studies on any given day, while treating about 500 patients in
clinical trials per year, the CTRC requires superior management, which, in addition to Dr. Karp, is provided by clinical
administrative director Cynthia Stewart, M.S., R.N. and
nurse manager Vivian Dorsey, R.N., B.S.N.
Stewart’s primary responsibilities as clinical administrative
director of the CTRC are staff recruitment, coordinating the CTRC
Steering Committee while helping
to screen protocols submitted for
CTRC support, and supervising the
laboratory and nursing care. Her
newest challenge has been the
laboratory, when all laboratory
responsibilities from sample
collection and storage to shipping
were moved to the CTRC in June,
2005. With the assistance of systems
analyst Jerry Gilbert, the CTRC is
in the process of automating an
electronic invoicing and billing
system. They are also exploring
development of other databases as
alternative to paper systems in the laboratory and nursing.
Dorsey feels that the main challenges she faces as nurse
manager of the CTRC are related to the tremendous growth
the center has experienced, since opening in October 2002.
“This growth is great because it demonstrates that the doctors
are aggressively searching for new agents and modalities to
treat cancer,” she concluded. In addition to providing
oversight and guidance to the CTRC staff, Dorsey works
with the research nurses and PIs to ensure accurate protocol
implementation and compliance.
“The CTRC’s greatest strength is our nursing care,” said
Stewart. “We have wonderful nurses,” Dr. Karp concurred.
Stewart added, “The CTRC is more nurse-run than a hospital.
CTRC nursing is highly autonomous and requires skilled
nurses who pay acute attention to detail. In collaboration
with the research teams, the nurses participate in a more
independent form of nursing that focuses on direct
transactions with the patients. A large part of the nurses’
responsibility is to make sure things go according to protocol.
The nurses become very familiar with the protocols and the
drugs they give.” She noted that one of the most important
functions of the nurses on the CTRC is anticipating side effects.
“They are very meticulous about observing side effects and not
missing symptoms that may be related to the study agent,” she
added. “They proactively ask the patients about symptoms like
pain because patients often do not report pain because they
think it’s normal with cancer. Instead, they may be experiencing
musculoskeletal pain from the medication.” The CTRC nurses
then communicate such information to the research team.
“The nurses see drug reactions often enough that they know
how to deal with them swiftly and skillfully so that the
patients are well protected and taken care of. As a result, the
patients are very satisfied. They love the nursing care they get
here, and they like the unit.”
A new measure introduced to improve quality control in the
CTRC is the conduction of an internal audit for each protocol
after the first or second patient has been entered into the study.
“This allows us to discover problems early enough to fix them,”
Dr. Karp noted. “Our goal is to have zero errors.”
Corresponding with growth in the Phase I Program, the
CTRC has been scrambling to expand its services and laboratory capacity to keep up with the increasing volume of protocols
and number of checkpoints and auditable events. The CTRC is
expanding their hours beyond the current 12 hours a day, five
days a week—first to 16 hours and eventually to a 24/7,
around-the-clock schedule. Stewart
is looking into redefining and
reorganizing the roles of the
clinical nurses, their background
and experience, and additional
training needs in research and
cardiac monitoring. She is currently
in the process of hiring a manager of
clinical protocol administration and
medical assistants. The protocol
manager will assist with development
of CTRC budgets and serve as a
liaison to the institution’s research
teams. The medical assistants will
assist with EKGs, vital signs, and
blood draws. With the rapid growth
in Phase I clinical trials, Stewart
foresees needing to build an adequate infrastructure, which
will include more nurses and other staff. “We want to recruit
and retain the best people while keeping teamwork and morale
at the highest level,” said Dr. Karp. “We’re planning for a big
future,” Stewart concluded.
PROTOCOL
PI & STUDY COORDINATOR
DRUG INFORMATION
DISEASES
COMMENT
Includes CNS metastases
Atiprimod
Razelle Kurzrock, M.D.
Fadi Braiteh, M.D.
Inhibits IL-6 & VEGF
Advanced cancers
MPC-6827
Razelle Kurzrock, M.D.
Terri Warren, R.N.
Razelle Kurzrock, M.D.
Fadi Braiteh, M.D.
Tubulin inhibitor
Good brain penetration
Hypomethylating agent (azacitidine)
with histone deacetylase
inhibitor (valproic acid)
Aziridine-derived iminopyrrolidone
depletes glutathione
Advanced cancers
Azacitidine & valproic acid
Advanced cancers
Includes CNS metastases
Advanced cancers,
non-small-cell lung,
breast, prostate)
Advanced cancers
Includes CNS metastases
Conventional chemotherapy
with proteosome inhibitor
Advanced cancers
Razelle Kurzrock, M.D.
Susan Pilat, R.N., B.S.N.
Razelle Kurzrock, M.D.
Susan Pilat, R.N., B.S.N.
Farnesyltransferase inhibitor
Razelle Kurzrock, M.D.
Susan Pilat, R.N., B.S.N.
Razelle Kurzrock, M.D.
Kathy Kehr, P.A.
Faye Johnson, M.D., Ph.D.
Naureet Dhillon, M.D.,
Joann Lim, PharmD, Ph.D.
Vali Papadimitrakopoulou, M.D.
Michelle Purdom, R.N.
David Stewart, M.D.
Kathy Kehr, P.A.C., B.S.
Roy Herbst, M.D., Ph.D.
Deborah Boughton, R.N.
Roy Herbst, M.D., Ph.D.
Deborah Boughton, R.N.
Roy Herbst, M.D., Ph.D.
Deborah Boughton, R.N.
David Hong, M.D.
Shobha Pai, P.A.
Adenosine deaminase inhibitor
Myelodysplastic
syndrome
Castleman’s disease,
lymphoid tumors,
myeloma
Lymphoid malignancy
Includes children any age.
No CNS metastases, requires
measurable disease, good left
ventricular function
(ejection fraction >50%)
Amplimexon & Taxotere
Razelle Kurzrock, M.D.
Navneet Dhillon, M.D.
XL 184
Razelle Kurzrock, M.D.
Il-Ran Hwang
Razelle Kurzrock, M.D.
Deborah Broughton, R.N.
Doxil, gemcitabine, & velcade
Tipifarnib
CNTO 328
Pentostatin
Curcumin
Ketoconazole & BMS-354825
RO 4584820
Low-dose decitabine
PRO 1762 (TRAIL)
AMG 706
AMG 386
Tipifarnib & Sorafenib
ZIO-101
Satraplatin
Satraplatin
Includes CNS metastases,
children 13 or older,
platelets 50,000 or more
Luis Camacho, M.D.
Charla Parker, R.N.
Luis Camacho, M.D.
Charla Parker, R.N.
Luis Camacho, M.D.
Charla Parker, R.N.
Met kinase & VEGFR inhibitor
Antibody against IL-6
No CNS metastases
Phase II
Plant-derived chemical,
inhibits NF-κB
Inhibits Src family of kinases
Pancreatic cancer
Phase II
Solid tumors
Includes CNS metastases,
requires biopsy
CDK inhibitor
Solid tumors
Hypomethylating agent
Advanced cancers
Includes CNS metastases;
requires biopsiable disease
Requires biopsiable disease
Tumor necrosis-related,
apoptosis-inducing ligand
Inhibits angiogenesis (VEGFR & Kit)
Solid tumors,
non-Hodgkin’s lymphoma
Solid tumors
No CNS metastases,
requires measurable disease
Closed to new patient accrual
Inhibits angiogenesis
Advanced solid tumors
Combines farnesyltransferase
inhibitor (tipifarnib) with raf kinase/
VEGFR inhibitor (sorafenib)
Organic arsenic derivative
Advanced cancers
No CNS metastases
Solid tumors
Includes children any age
Oral platinum
Solid tumors
Oral platinum
Solid tumors
Includes renal impairment
& CNS metastases
Includes hepatic impairment
& CNS metastases
THE UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER
Continued on reverse side
Active Protocols continued
PROTOCOL
PI & STUDY COORDINATOR
Luis Camacho, M.D.
Charla Parker, R.N.
Cytotoxic, combined regional
& systemic chemotherapy
Advanced cancers
Liver predominant diseases
Hepatic arterial infusion
of Taxol
Luis Camacho, M.D.
Charla Parker, R.N.
Cytotoxic regional therapy
Advanced cancers
Liver predominant diseases
Hepatic arterial
infusion of cisplatinum
with IV Doxil
Monoclonal antibodies
DRUG INFORMATION
DISEASES
COMMENT
Antibody production
Solid tumors
Non-therapeutic
Suberoylanilide hydroxamic
acid, Pemetrexed, & Cisplatin
Luis Camacho, M.D.
Charla Parker, R.N.
George Blumenschein, Jr., M.D.
Forlisa Nauling, R.N.
Histone deacetylase
inhibitor with chemotherapy
Solid tumors
Imaging reproducibility study
Lung & liver malignancy
Includes CNS metastases,
requires measurable disease
Non-therapeutic
PROTOCOL
PRINCIPAL INVESTIGATOR
DRUG INFORMATION
DISEASES
COMMENT
DCE MRI, dynamic contrast
enhancement MRI, & dynamic
contrast enhancement CT
Chaan Ng, M.D.
Terri Warren, R.N.
PI-0052
Razelle Kurzrock, M.D.
Proteosome inhibitor
Apomab
Roy Herbst, M.D., Ph.D.
E 7080
David Hong, M.D.
Antibody stimulates apoptosis by
triggering caspase activation
Advanced or metastatic
solid tumors
MPC-6827
Luis Camacho, M.D.
Combines 2 anti-angiogenic agents
Advanced solid tumors
Liposomal platinum
Solid tumors
AMG 655
AMG 386 & AMG 706
Roy Herbst, M.D., Ph.D.
David Hong, M.D.
Aroplatin
Luis Camacho, M.D.
LY 2275796
Yun Oh, M.D.
Oncophage (HSPPC-96)
& ATRA-IV
Luis Camacho, M.D.
TRAIL receptor-binding,
tumor growth inhibitor
Angiogenesis inhibitor
Tubulin inhibitor
Good brain penetration
Liposomal tretinoin & autologous
tumor-derived peptide vaccine
Antisense, inhibits eukaryotic
initiation factor
Advanced cancers
Solid tumors
Advanced cancers
Advanced cancers
Renal cell carcinoma,
metastatic melanoma,
NSCLC, liver metastases from
colorectal cancer
Advanced cancers
Refractory brain metastases
Includes CNS metastases
Phase I Retreat continued from
•••••••••••••••••••••••
Director, Phase I Program
Chair, Phase I Working Group
Professor, Division of Cancer Medicine
Razelle Kurzrock, M.D., F.A.C.P
Phone: (713) 794-1226 • Pager: (713) 404-2397
E-mail: rkurzroc@mdanderson.org
Co-Chair, Phase I Working Group
Associate Professor, Dept. of Thoracic/Head
and Neck Medical Oncology
Roy S. Herbst, M.D., Ph.D.
Phone: (713) 792-6363 • Pager: (713) 404-6323
E-mail: rherbst@mdanderson.org
Co-Chair, Phase I Working Group
Chief, Section of Developmental Therapeutics
and Professor, Dept. of Leukemia
Francis J. Giles, M.D.
Phone: (713) 792-8217 • Pager: (713) 404-4621
E-mail: fgiles@mdanderson.org
Assistant Professor, Phase I Program
and Dept. of Melanoma
Luis H. Camacho, M.D.
Phone: (713) 792-5252 • Pager: (713) 404-5319
E-mail: lhcamach@mdanderson.org
Assistant Professor, Phase I Program
David Hong, M.D.
Phone: (713) 792-2740 • Pager: (713) 404-0560
E-mail: dhong@mdanderson.org
Clinical Administrative Director
Cynthia D. Stewart, R.N., M.S.N.
Phone: (713) 792-7996 • Pager: (713) 404-2802
E-mail: cstewart@mdanderson.org
Research Nurse Supervisor
Susan R. Pilat, R.N., B.S.N.
Phone: (713) 745-3296 • Pager: (713) 404-2822
E-mail: spilat@mdanderson.org
Research Nurse Supervisor
Michelle A. Purdom, R.N.
Phone: (713) 794-5177 • Pager: (713) 404-2989
E-mail: mapurdom@mdanderson.org
Editor
Carol A. Howland, M.S.
Graphic Design/Photography
Medical Graphics & Photography
Phase I Clinical Trials Program
Division of Cancer Medicine
The University of Texas
M. D. Anderson Cancer Center
1515 Holcombe Boulevard
Houston, Texas 77030-4009
page 1
0.5 percent death rate from toxic events,
which is extraordinary considering that
patients entering these studies by definition
have terminal progressive cancer and are
expected to live only a few months.”
There was concordance among participants that some of the regulatory requirements
that were put in place to enhance patient
safety, in fact, often served to compromise the
individual patient’s welfare. For instance, once
patients enter a protocol, if they want to
continue receiving the drug, they have to
follow the protocol exactly, even if certain
protocol specifications are not in their best
interest or interfere with important events in
their lives. Daniel Karp, M.D. added that the
goal of the pharmaceutical industry is to get
the drug approved and we need to stay aware
of the natural conflict of interest inherent in
that goal when dealing with individual patients.
Participants voiced the fears that we will
end up regulating ourselves out of business and
that investigator-initiated studies are particularly under siege. “Investigator-initiated studies
are likely to lead to important new discoveries
because they capitalize on the ‘M.D. Anderson
Cancer Center brain trust,’ i.e., the expertise
that faculty bring to M. D. Anderson,”
Dr. Kurzrock remarked. “It is critical that we
overcome these barriers.”
Dr. Stewart added, “We need to be smarter
about how we word our protocols so we don’t
add more than is necessary to comply with
federal regulations. The standard should be the
code of federal regulations, not beyond.” This
burgeoning regulatory burden has, in turn,
increased the need for more research nurses
and coordinators in the midst of a nationwide
nursing shortage. Development of a study
coordinator course is one solution under
examination by Maurie Markman, M.D.,
vice president for clinical research.
Dr. Kurzrock emphasized the need for
teamwork within the program and collaboration with others to support the program’s
growth. “The success of the program so far
can be credited largely to a wonderful group of
hard-working people who are committed to
making things happen.”
Dr. Giles introduced the cultural issue of
the most appropriate home for Phase I studies
within M. D. Anderson—residing in each
department vs. a centralized program for
broad-based Phase I studies. Dr. Kurzrock
emphasized that the Phase I Program does
only broad Phase I studies that cross disease
boundaries, which hasn’t had a home at
M. D. Anderson. “We are a difficult cultural fit
in a disease-centered institution,” she said.
“But based on the success and demand for the
program so far, it appears that this program fills
an important gap in the institutional clinical
research infrastructure.” Addressing concerns
about direct patient referral to the Phase I
Program, Dr. Kurzrock said, “These patients
are not accepted by other groups once they
have exhausted other therapies. They must be
allowed in somewhere. Cultural issues must
not overcome common sense issues.” Dr. Karp
added, “This is an unmet need. We must have
a front door policy and do our part to get
patients to the right place.”
The Phase I retreat wrapped up with discussion of the following goals:
• Move the program toward personalized therapy, fingerprinting patients to predict potential response,
and identify preliminary subsets of responsive patients to use as a foundation for Phase II studies.
• Have a large number of high-impact studies, aiming to investigate “the best molecules in the nation.”
• Emphasize strongly the quality of patient care, keeping in mind that the patient must always come
first, not the study.
• Enhance the capacity of Phase I studies to serve as a conduit to Phase II efficacy studies, especially for
uncommon tumors, so that early evidence of response can be quickly translated into new treatment.
• Continue to foster team work and a collaborative atmosphere both within the program and in its
interactions with other investigators throughout the institution, so that the ultimate goal of bringing
new therapies to cancer patients can be met.
• Further develop the Phase I infrastructure, from faculty to research nurses, coordinators and other
personnel, in order to support program growth and excellence.