publication date: Apr. 17, 2020

Doroshow: NCI to accrue patients for COVID-19 longitudinal cohort

Ongoing trials see significant decrease in accrual

By Matthew Bin Han Ong

This story is part of The Cancer Letter’s ongoing coverage of COVID-19’s impact on oncology. A full list of our coverage, as well as the latest meeting cancellations, is available here.

NCI is building a nationwide cohort of cancer patients with COVID-19 at over 1,000 sites across the institute’s clinical trials networks and at NCI-designated cancer centers.

Patient accrual is scheduled to begin before May 15, with a target of at least 2,000 patients nationwide by Dec. 1. Sites participating in the institute’s Cancer and COVID-19 Longitudinal Cohort can count on full reimbursement for each patient enrolled, NCI officials said.

“We have patients, we have institutions that want to participate in learning more about this situation in cancer patients,” James Doroshow, deputy director for clinical and translational research at NCI, said April 9 in an emergency virtual meeting of the NCI Board of Scientific Advisors and the National Cancer Advisory Board. “We clearly have the resources to allow full case reimbursement for participation in this longitudinal trial across all the various networks that we have.

“We also very definitely need to enroll, because of the data that we are now starting to see about the ravages of COVID-19 in minority patients who have cancer, we very much need to enlist the help of our minority NCORP sites to try to accrue to this cohort,” said Doroshow, who is also director of NCI’s Division of Cancer Treatment and Diagnosis and head of the Oxidative Signaling and Molecular Therapeutics Group of NCI’s Developmental Therapeutics Branch.

The study’s goals are to:

  • Accrue cancer patients infected with COVID-19 comprising all age groups for collection of a comprehensive dataset on the cancers, treatments, medications, symptoms, course, and recovery, and co-morbidities with longitudinal follow-up every 1-2 months until return to pre-morbid status,

  • Follow subset of patients for over a year to assess impact of COVID-19 on survivorship and quality of life,

  • Collect blood samples at study entry and then every two months for a year to estimate antibody response, genetic susceptibility, and for biomarker development; collect blood from family members, and

  • Create a public database of biospecimens.

“The infrastructure is being built as we speak, with all of the infrastructure that NCI has,” Doroshow said. “I have basically refocused the entirety of the NCI’s clinical trials research enterprise.”

 

Doroshow’s remarks to BSA and NCAB follow:

I appreciate the opportunity to discuss with this group what we’ve been doing over the past several weeks at the NCI to address some of the clinical trials and clinical research issues that all of us are feeling very acutely.

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This is some recent data from hospitals in Wuhan. We know that the cancer patients who get COVID-19 are predominantly male.

The death rate is really pretty extraordinary, associated with the high ICU admission rate. The thing that is also becoming clear is that it’s patients with advanced disease, lung cancer and metastatic cancer, that may be at the highest risk of dying from infections.

I just think it’s important once again, for all of us to express our appreciation to the enormous numbers of health professionals who are trying to help cancer patients everywhere, both in inpatient and outpatient settings, patients with this virus. It is really an incredible endeavor to try to maintain standard of care for these patients.

Let me give you some data regarding what the coronavirus infection has done to accrual to NCI at clinical trials. This is a table for data up through the end of March. I have data as well for the following week. It’s for interventional trials, and for the various NCTN groups.

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Decrease in accrual for trials

What you can see is that we were cruising along through February and most of March at a standard 300 patients per week accrual to interventional trials. Then, the cliff hit at the last week of March, down about 45% to 50% in terms of accrual across the board, from organization to organization. That’s true as well for the first week of April.

It turns out that of course, it’s not just the interventional studies, but screening trials—trials that involve a screening step before the intervention is assigned—have also taken a very similar nosedive.

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I think that these numbers are not surprising, and furthermore, they not only apply to all of our NCTN groups, but basically the data for all NCI clinical trials networks. The early clinical trials networks, our immunotherapy networks across the board, trial accrual is down about 45% to 50%, and is certainly consistent with the fact that many institutions have shut down accruals in most of their studies, and in particular, in New York, the accrual rates have plummeted, because it’s really an all-hands-on-deck situation, where physicians are really needed to take care of this enormous patient load.

I wanted to point, however, that that’s not true universally, that there are some institutions that have been able to accrue some patients—that’s true at the [NIH] Clinical Center, true at some other organizations.

And, I think where that is reasonable is with respect to the studies that offer patients curative therapy. And so, it would seem to me that patients with acute myelogenous leukemia, or advanced lymphoma, who have curable diseases that really can benefit from treatment on studies where it’s possible to do that, as well as patients who really have no other therapeutic options. I think as it’s been pointed out by many of the folks on the line, accrual to non-therapeutic studies has taken a much greater hit across all of our networks.

 

COVID-19 Longitudinal Cohort

Now, I’d like to come to this longitudinal cohort that we’ve been working on that Doug referred to. This is really something that is, as far as I’m concerned, if we can do this, then we can change the entire NCI-supported clinical trial system. We started about two weeks ago or less, on developing a large cohort.

We don’t know what the final cohort size is going to be, because the sample size estimates are ongoing, to develop a way to collect data across all of the NCI sites across the NCTN, across the ETCTN, across NCORP, at cancer centers, to include high, moderate, and currently low-prevalence regions. And, we’re going to do this, not only because it’s the right thing to do, but also because, as you saw in the numbers, our accrual is down 50%.

We have patients, we have institutions that want to participate in learning more about this situation in cancer patients. It’s a special situation, and since all of our sites were re-funded for the full 2020 academic fiscal year just last month, we clearly have the resources to allow full case reimbursement for participation in this longitudinal trial across all the various networks that we have.

We also very definitely need to enroll, because of the data that we are now starting to see about the ravages of COVID-19 in minority patients who have cancer, we very much need to enlist the help of our minority NCORP sites to try to accrue to this cohort.

The infrastructure is being built as we speak, with all of the infrastructure that NCI has. I have, with Ned’s permission, basically refocused the entirety of the NCI’s clinical trials research enterprise to be able to put up a trial on the [Clinical Trials Support Unit], to develop blood banking, to enlist the NCI CIRB to develop case report forms with a collaborative extramural NCI leadership team that has basically started a working group about 10 days ago, is meeting daily. It has representation from all of the appropriate specialties, with the goal of developing a cohort of all aged patients, to have a comprehensive data set for treatment, medications, course recovery, comorbidities, with follow-up regularly over the course of about a year.

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We want to follow subsets of patients for longer than a year to understand the impact of COVID-19 on cancer survivorship and quality of life. We pointed at the regularly collecting blood samples at entry, and then at regular intervals to estimate antibody response, genetic susceptibility, to develop biomarkers, and to collect blood eventually from family members.

And, all of this data will be up in a public website, and the biospecimens will be available for the research community to share as this moves forward.

We hope to actually have a trial up and going by the second week of May. We actually have a goal of having a written protocol document next Monday. That’ll be two weeks to get a full document up and running, to enroll our first 500 patients within the three months of activation; complete accrual by the end of this calendar year and survivorship evaluation for the end of 2020. And then, rapidly begin biomarker studies on the samples, as soon as the initial 500 patients are accrued.

I don’t want to end, because it would be very inappropriate to do so without calling out the more than a dozen NCI-designated cancer centers who’ve developed their own therapeutic trials for cancer patients.

Now, I only know about a dozen, because there were at least a dozen NCI-designated centers that submitted requests for supplemental funds for clinical trials that are being carried on at their institutions. There may be many, many more. But, there are a wide range of activities that have been sponsored, and are being sponsored locally, which we really might need to be able to support.

I also want to call out the Vanderbilt Comprehensive Cancer Center, who stood up, beginning this past Monday, their COVID-19 and Cancer Consortium, that will use de-identified information, open access to Internet database, that is now endorsed by over 70 cancer centers, hospital systems, and large practices, to rapidly get information that will be useful for clinical practice.

And also, we shouldn’t neglect our colleagues in pharma, who have several ongoing phase III trials of IL-6 receptor antibodies, or antivirals, and other activities in the cancer space that will contribute to this entire amount of information that has been stood up in just a remarkably short period of time.

I wanted to thank all of these individuals across the NCI, as well as collaborators at Vanderbilt and several other extramural cancer centers, who have come together to help us put together this large cohort, and also who are involved intimately in the standing up of the kinds of data collection systems, and biosample collections, that we will need to really understand the impact of COVID-19 on cancer patients.

And finally, I think it is not unreasonable to suggest that this whole episode demonstrates that the NCI, working with its grantees, really can be flexible to try to do something that is timely in a major national emergency.

 

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