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Posts Tagged ‘interventional oncology’


 

Multiple factors related to initial trial design may predict low patient accrual for cancer clinical trials

Reporter: Stephen J. Williams, Ph.D.

UPDATED 5/15/2019

A recently published paper in JCNI highlights results determining factors which may affect cancer trial patient accrual and the development of a predictive model of accrual issues based on those factors.

To hear a JCNI podcast on the paper click here

but below is a good posting from scienmag.com which describes their findings:

Factors predicting low patient accrual in cancer clinical trials

source: http://scienmag.com/factors-predicting-low-patient-accrual-in-cancer-clinical-trials/

Nearly one in four publicly sponsored cancer clinical trials fail to enroll enough participants to draw valid conclusions about treatments or techniques. Such trials represent a waste of scarce human and economic resources and contribute little to medical knowledge. Although many studies have investigated the perceived barriers to accrual from the patient or provider perspective, very few have taken a trial-level view and asked why certain trials are able to accrue patients faster than expected while others fail to attract even a fraction of the intended number of participants. According to a study published December 29 in the JNCI: Journal of the National Cancer Institute, a number of measurable trial characteristics are predictive of low patient accrual.

Caroline S. Bennette, M.P.H., Ph.D., of the Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, and colleagues from the University of Washington and the Fred Hutchinson Cancer Research Center analyzed information on 787 phase II/III clinical trials sponsored by the National Clinical Trials Network (NCTN; formerly the Cooperative Group Program) launched between 2000 and 2011. After excluding trials that closed because of toxicity or interim results, Bennette et al. found that 145 (18%) of NCTN trials closed with low accrual or were accruing at less than 50% of target accrual 3 years or more after opening.

The authors identified potential risk factors from the literature and interviews with clinical trial experts and found multiple trial-level factors that were associated with poor accrual to NCTN trials, such as increased competition for patients from currently ongoing trials, planning to enroll a higher proportion of the available patient population, and not evaluating a new investigational agent or targeted therapy. Bennette et al. then developed a multivariable prediction model of low accrual using 12 trial-level risk factors, which they reported had good agreement between predicted and observed risks of low accrual in a preliminary validation using 46 trials opened between 2012 and 2013.

The researchers conclude that “Systematically considering the overall influence of these factors could aid in the design and prioritization of future clinical trials…” and that this research provides a response to the recent directive from the Institute of Medicine to “improve selection, support, and completion of publicly funded cancer clinical trials.”

In an accompanying editorial, Derek Raghavan, M.D., Levine Cancer Institute, writes that the focus needs to be on getting more patients involved in trials, saying, “we should strive to improve trial enrollment, giving the associated potential for improved results. Whether the basis is incidental, because of case selection bias, or reflects the support available to trial patients has not been determined, but the fact remains that outcomes are better.”

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Contact info:

Article: Caroline S. Bennette, M.P.H., Ph.D., cb11@u.washington.edu

Editorial: Derek Raghavan, M.D., derek.raghavan@carolinashealthcare.org

Other investigators also feel that initial trial design is of UTMOST importance for other reasons, especially in the era of “precision” or “personalized” medicine and why the “basket trial” or one size fits all trial strategy is not always feasible.

In Why the Cancer Research Paradigm Must Transition to “N-of-1” Approach

Dr. Maurie Markman, MD gives insight into why the inital setup of a trial and the multi-center basket type of  accrual can be a problematic factor in obtaining meaningful cohorts of patients with the correct mutational spectrum.

The anticancer clinical research paradigm has rapidly evolved so that subject selection is increasingly based on the presence or absence of a particular molecular biomarker in the individual patient’s malignancy. Even where eligibility does not mandate the presence of specific biological features, tumor samples are commonly collected and an attempt is subsequently made to relate a particular outcome (eg, complete or partial objective response rate; progression-free or overall survival) to the individual cancer’s molecular characteristics.

One important result of this effort has been the recognition that there are an increasing number of patient subsets within what was previously—and incorrectly—considered a much larger homogenous patient population; for example, non–small cell lung cancer (NSCLC) versus EGFR-mutation–positive NSCLC. And, while it may still be possible to conduct phase III randomized trials involving a relatively limited percentage of patients within a large malignant entity, extensive and quite expensive effort may be required to complete this task. For example, the industry-sponsored phase III trial comparing first-line crizotinib with chemotherapy (pemetrexed plus either carboplatin or cisplatin) in ALK-rearrangement–positive NSCLC, which constitutes 3% to 5% of NSCLCs, required an international multicenter effort lasting 2.5 years to accrue the required number of research subjects.1

But what if an investigator, research team, or biotech company desired to examine the clinical utility of an antineoplastic in a patient population representing an even smaller proportion of patients with NSCLC such as in the 1% of the patient population with ROS1 abnormalities,2 or in a larger percentage of patients representing 4%-6% of patients with a less common tumor type such as ovarian cancer? How realistic is it that such a randomized trial could ever be conducted?

Further, considering the resources required to initiate and successfully conduct a multicenter international phase III registration study, it is more than likely that in the near future only the largest pharmaceutical companies will be in a position to definitively test the clinical utility of an antineoplastic in a given clinical situation.

One proposal to begin to explore the benefits of targeted antineoplastics in the setting of specific molecular abnormalities has been to develop a socalled “basket trial” where patients with different types of cancers with varying treatment histories may be permitted entry, assuming a well-defined molecular target is present within their cancer. Of interest, several pharmaceutical companies have initiated such clinical research efforts.

Yet although basket trials represent an important research advance, they may not provide the answer to the molecular complexities of cancer that many investigators believe they will. The research establishment will have to take another step toward innovation to “N-of-1” designs that truly explore the unique nature of each individual’s cancer.

Trial Illustrates Weaknesses

A recent report of the results of one multicenter basket trial focused on thoracic cancers demonstrates both the strengths but also a major fundamental weakness of the basket trial approach.3

However, the investigators were forced to conclude that despite accrual of more than 600 patients onto a study conducted at two centers over a period of approximately 2 years, “this basket trial design was not feasible for many of the arms with rare mutations.”3

They concluded that they needed a larger number of participating institutions and the ability to adapt the design for different drugs and mutations. So the question to be asked is as follows: Is the basket-type approach the only alternative to evaluate the clinical relevance of a targeted antineoplastic in the presence of a specific molecular abnormality?

Of course, the correct answer to this question is surely: No!

– See more at: http://www.onclive.com/publications/Oncology-live/2015/July-2015/Why-the-Cancer-Research-Paradigm-Must-Transition-to-N-of-1-Approach#sthash.kLGwNzi3.dpuf

The following is a video on the website ClinicalTrials.gov which is a one-stop service called EveryClinicalTrial to easily register new clinical trials and streamline the process:

 

UPDATED 5/15/2019

Another possible roadblock to patient accrual has always been the fragmentation of information concerning the availability of clinical trails and coordinating access among the various trial centers, as well as performing analytics on trial data to direct new therapeutic directions.  The NIH has attempted to circumvent this problem with the cancer trials webpage trials.gov however going through the vast number of trials, patient accrual requirements, and finding contact information is a daunting task.  However certain clinical trial marketplaces are now being developed which may ease access problems to clinical trials as well as data analytic issues, as highlighted by the Scientist.com article below:

Scientist.com Launches Trial Insights, A Transformative Clinical Trials Data Analytics Solution

The world’s largest online marketplace rolls out first original service, empowering researchers with on demand insights into clinical trials to help drive therapeutic decisions

SAN DIEGO–(BUSINESS WIRE)–Scientist.com, the online marketplace for outsourced research, announced today the launch of Trial Insights, a digital reporting solution that simplifies data produced through clinical trial, biomarker and medical diagnostic studies into an intuitive and user-friendly dashboard. The first of its kind, Trial Insights curates publicly available data nightly from information hubs such as clinicaltrials.gov and customizes it to fit a researcher or research organization’s specific project needs.

Trial Insights, new clinical trial reporting solution, allows researchers to keep track of the evolving landscape of drugs, diseases, sponsors, investigators and medical devices important to their work.

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“Trial Insights offers researchers an easy way to navigate the complexity of clinical trials information,” said Ron Ranauro, Founder of Incite Advisors. “Since Trial Insights’ content is digitally curated, researchers can continuously keep track of the evolving landscape of drugs, diseases, sponsors, investigators and medical devices important to their work.”

As the velocity, variety and veracity of data available on sites like clinicaltrials.gov continues to increase, the ability to curate it becomes more valuable to different audiences. With the advancement of personalized medicine, it is important to make the data accessible to the health care and patient communities. Information found on the Trial Insights platform can help guide decision making across the pharmaceutical, biotechnology and contract research organization industries as clinical trial data is a primary information source for competitive intelligence, research planning and clinical study planning.

“We are extremely excited to launch the first Scientist.com exclusive, original service offering to our clients in the life sciences,” said Mark Herbert, Scientist.com Chief Business Officer. “Our goal at Scientist.com is to help cure all diseases by 2050, and we believe solutions like Trial Insights, which greatly simplifies access to and reporting of clinical trial data, will get us one step closer to reaching that goal.”

source: https://www.businesswire.com/news/home/20190416005362/en/Scientist.com-Launches-Trial-Insights-Transformative-Clinical-Trials?utm_source=TrialIO+List

 

Other article on this Open Access Journal on Cancer Clinical Trial Design include:

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State-of-the-Art Procedures in Interventional Oncology –

Curator; Larry H. Bernstein, MD, FCAP

LPBI

Vascular and Interventional Radiology

http://www.hopkinsmedicine.org/vascular/conditions/oncology_interventional.html

Oncology

The Johns Hopkins interventional radiology physicians play a critical role as part of the Cancer Center team. Ours is a rapidly evolving field where innovative techniques for both diagnosing and treating cancer are now available resulting in prolonged quality survival for patients with cancer.

Therapeutic Procedures

  • Tumor ablation
    • Cryoablation
    • Radiofrequency ablation (RFA)
    • Microwave ablation

Supportive Procedures

  • Paracentesis or Thoracentesis
  • PICC line placement
  • Tunneled catheter placement
  • Port catheter placment
  • Percutaneous biliary drainage
  • Percutaneous nephrostomy
  • Pleurx catheter placement
  • Stenting of malignant strictures: bile duct, esophageal, tracheobronchial and intestinal
  • Portal vein embolization

Interventional Oncology

Interventional oncology, practiced by interventional radiologists, is one of four parts of a multidisciplinary team approach in the treatment of cancer and cancer related disorders. The others  include medical oncology, surgical oncology and radiation oncology.

Interventional oncology procedures provide minimally invasive, targeted treatment of cancer. Image guidance is used in combination with the most current innovations available to treat cancerous tumors while minimizing possible injury to other body organs. Most patients having these procedures are outpatients or require a one night stay in the hospital.

  • Some of these therapies are regional, as when treating cancers involving several areas of the liver with chemoembolization or radioembolization.
  • Others are better classified as local, as when treating focal lesions in the kidney, liver, lung and bone with cryoablation (freezing), or microwave or radiofrequency ablation (heating).

In general, these techniques are reserved for patients whose cancer cannot be surgically removed or effectively treated with systemic chemotherapy. These procedures are also frequently used in combination with other therapies provided by other members of the cancer team.

Burgeoning Field of Interventional Oncology Is Poised for Takeoff

A Q&A With Dan Brown, MD –

http://www.onclive.com/publications/obtn/2013/November-2013/Burgeoning-Field-of-Interventional-Oncology-Is-Poised-for-Takeoff-A-QandA-With-Dan-Brown-MD#sthash.qeToPGBm.dpuf

Andrew J. Roth @andrewjohnroth

Interventional oncology is an emerging field in cancer care that is intended to complement existing treatment modalities. We sat down with Dan Brown, MD, the new chief of Interventional Oncology at Vanderbilt University Medical Center, to discuss the burgeoning field and its potential effect on cancer care moving forward.

OBTN: What is interventional oncology and how does it fit in with the current cancer treatment paradigm?

Dr. Brown: Interventional oncology uses image-guided technology to directly target solid tumors. It’s a complementary intervention that I hope will eventually be integrated into standard care algorithms. It gives clinicians another focused area of cancer care in which we can collaborate with other specialists. We perform targeted procedures that can be characterized as either arterial or ablative. Interventional oncology, and to some extent interventional radiology, also involves the use of biopsies for genomics analysis, in a similar way as other oncologic specialists use biopsies to help guide their biological therapies or systemic therapies.

Which patients are likely candidates for interventional oncology and how are they identified?

Vanderbilt is the second place in the country to have a formal division of interventional oncology and a backbone of our program is tumor boards. I participate in at least three tumor boards a week involving specialists in gastrointestinal oncology, liver transplantation, and neuroendocrine tumors.

The cornerstone tumor for interventional oncology is probably hepatocellular carcinoma. Chemoembolization is one of the older procedures that we perform dating back to 1980. And it became standard of care because, quite frankly, there was nothing else for years that did anything. Now we perform it very frequently. We see this in the transplant population or potential transplant population— we want to prevent patients from progressing beyond Milan criteria or to try to downstage patients back to Milan criteria if they’re beyond it.

In patients with colorectal cancer, we can either try to get a patient to surgery with portal vein embolization or we will perform radioembolization of liver metastases or ablation of liver metastases based on where they stand with their chemotherapy. If patients get toxicity from chemotherapy, particularly neurotoxicity after FOLFOX, and have residual liver disease, sometimes we treat them to give them time off of systemic therapy.

We treat a lot of patients with neuroendocrine tumors here at Vanderbilt. We perform radioembolization and bland embolization for those patients. For patients with hepatocellular and colorectal metastases, our first goal is to get them to surgery, either transplant or resection, as these treatments are potentially curative.

Can you discuss in detail some of the procedures involved with interventional oncology?

There are two main techniques that we perform— arterial interventions and ablation. For liver cancer, arterial treatment involves threading a catheter through the femoral artery to reach the primary tumor (Figure 1). The strategy is to use the tumor’s vasculature to deliver microscopic beads that contain radioactive materials or chemotherapy into the tumor. The beads leach out the chemotherapy over the course of several weeks.

Figure 1. Hepatocellular carcinoma in a poor surgical candidate. The goal was to limit progression of disease through arterial intervention to allow transplant.

Dan-Brown-figure1 hepatocellular CA

Dan-Brown-figure1 hepatocellular CA

http://www.onclive.com/_media/_upload_image/Dan-Brown-figure1.jpg

a. 3-cm mass in the right lobe of the liver.

b. Catheter selecting the artery supplying the mass with enhancement of the tumor.

c. Complete tumor necrosis at follow-up imaging.

We can also infuse radioembolics in a similar way. There are two devices available—one is made of glass and the other is made of resin. In our practice, we’re treating more and more people with the radioembolic treatment because it’s an outpatient procedure. We’re starting to accumulate more data using the radioembolic treatment, especially for colon cancer and neuroendocrine tumors.

Radiofrequency ablation involves delivering an electrode into a tumor and passing a current through it. This raises the temperature in the tumor to about 60° Celsius, and kills it. Microwave ablation is a newer method used to destroy tumors with heat. It’s much more powerful, but its use is not as widespread. Finally, we can freeze tumors with cryoablation (Figure 2); this method will destroy tumor cells or regular noncancerous cells as well. Cryoablation is favored in small kidney masses, because the clinician can see the ice ball when it’s created. This has been very successful, and causes less pain than ablation that uses heat. And all these ablation types can be used in the kidney.

Figure 2. Renal cell carcinoma undergoing cryoablation in a patient who is not eligible for surgery.

Dan-Brown-figure2 RCC

Dan-Brown-figure2 RCC

http://www.onclive.com/_media/_upload_image/Dan-Brown-figure2.jpg

a. 3.5-cm left renal mass at baseline.
b. Ice ball at the end of CT-guided cryoablation.
c. Complete tumor necrosis 4 years after treatment.

We’ve seen a shift toward more radioembolization use. One product approved for treating hepatocellular carcinoma is TheraSphere, an FDA approved microsphere agent. SirSpheres are FDA approved for use in colorectal cancer with adjuvant chemotherapy. There are a number of prospective randomized trials going on worldwide that combine its use with first- and second-line chemotherapy regimens, and some of the first of those is called SIRFLOX. The study is designed to evaluate whether FOLFOX chemotherapy in combination with Selective Internal Radiation Therapy is more effective than chemotherapy alone. That should have data coming out some time next spring, when the data are mature enough to start analyzing.

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