Cancer isnt waiting for Covid-19 to go away. Neither is Karen Howley.

Diagnosed two years ago with advanced ovarian cancer, Howley started on a new experimental drug in mid-March, just as coronavirus case counts were soaring in Massachusetts. Her treatment, part of a clinical trial at Dana-Farber Cancer Institute in Boston, began with a four-week hospital stay, and since then, shes been returning every Monday for infusions.

While the study drug dripped into her body, she heard the hospital staff apprehensively discussing the coming surge of cases. Howley felt safe on a floor devoted to cancer patients, where there was no shortage of personal protective gear for the medical workers, but she still wiped down her tray each time a a meal was delivered to her bedside.

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Ambulance sirens wailing endlessly outside her window made her anxious. The hospitals no-visitor policy made her lonely. But Howley, who has faced her cancer with both humor and realism, never considered quitting the clinical trial.

I dont think it occurred to me, Howley, 56, said during an infusion appointment last week that she wryly called her spa day.

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Treatment for me is prolonging my life at this point. And if I do get Covid, I do.

Around the world, Covid-19 has disrupted all types of clinical trials, decreasing by 74% the number of new patients enrolling. In cancer, the number of new patients entering Phase 2 and 3 cancer trials in the U.S. plummeted by about 46% to 48% in the last two weeks of March, said Margaret Mooney, associate director of the Cancer Therapy Evaluation Program in the Division of Cancer Treatment and Diagnosis at the National Cancer Institute. By the last week of May and first week of June, the cliff wasnt so steep, moderating to a 25% to 30% decline.

Some medical centers put certain research trials on hold, stretched too thin by the needs of treating Covid-19 patients. Others continued their cancer trials by taking advantage of NCI-modified protocols allowing patient consent by phone or delivery of oral drugs to patients homes. Depending on where an individual site was located, they made local decisions that were best for their patients and their patient population in terms of clinical trials, Mooney said.

At Dana-Farber, Ursula Matulonis, chief of gynecologic oncology and Howleys oncologist, recalled patients feeling frightened and doctors feeling uncertain about exactly how they would carry on in the early days of the pandemic but no one ever doubted that they would.

We said, look, weve got to go in to see our patients because theyve got cancer. They want to continue to be treated in the same way, she said. We have a job to do and we have to continue to do that job.

Doing that job at Dana-Farber means patients are screened for symptoms when they enter the cancer center and at each step along the way. Howley answers the same set of questions Any fever? Any cough? Any contact with anyone who has Covid-19? when she has her vitals checked, gets her blood drawn, sees her doctor, receives her infusion.

Shes used to the waiting-room chairs zip-tied in opposite directions to keep single patients (no more friends or family) from getting too close. She expects to park her own car rather than turn it over to a valet. Because shes enrolled in a research trial, there are more blood samples taken for analysis and for tracking her response to the drug, but the entire visit moves along more quickly now, streamlined to reduce waiting times so no patient is exposed longer than necessary to other people.

Andrew Wagner, an oncologist who is leading Dana-Farbers efforts to keep patients safe and on treatment during Covid-19, said in consultation with study sponsors, some tissue biopsies were canceled, or for some patients chemotherapy was adjusted from every week to every three weeks. Physician visits to discuss imaging scans moved from in-person to video. Dana-Farber had zero telemedicine before March, but virtual visits now account for just under half of patient appointments, holding lessons for the future.

Its been hard in oncology, of course. Such a large part of what we do is the emotional care of patients and their families, Wagner said. Being able to hold someones hand is really hard to do through telemedicine, but certainly the video aspect of it is much better than just the telephone. Youre able to express yourself empathically.

Patient visits to Dana-Farber plunged by 40% in the course of one week in mid-March but chemotherapy appointments slipped by only 10% to 15% over that same week. Now doctors are encouraging patients to come back in. We think that its very safe here. We are certainly safer than in the grocery store, Wagner said. Cancer is not going to wait for Covid to go away.

Other cancer centers made similar adjustments. At the Ohio State University Comprehensive Cancer Center in Columbus, where close to 1,000 clinical trials are typically underway, Ohio Gov. Mike DeWines March 23 stay-at-home policy kept 200 research nurses and other staffers away from their duties. That meant only trials with a critical therapeutic outcome, extremely modest staffing needs, or time-sensitive enrollment targets continued, said Raphael Pollock, director of the cancer center.

Now that Ohios stay-at-home policy has been lifted and the research machinery is gearing up again, he expects trial participation to tick back up, too. Cancer didnt take time off, Pollock said. Well be quite busy by the mid- to late summer.

And at Memorial Sloan Kettering Cancer Center in New York City, the U.S. epicenter of the pandemic, no therapeutic trials were put on hold, but in-clinic volume in March and April did drop by about 75%. Telemedicine helped, said Paul Sabbatini, an oncologist and deputy physician-in-chief for clinical research. We and most centers have developed processes to rationally deal with the Covid risk as best we can so [clinical trials] can proceed now.

Now patients are coming back.

While it was prudent for patients to avoid the medical setting when the pandemic was at peak, enough time has elapsed that many of those patients clearly now have a benefit/risk ratio in favor of care, Sabbatini said. Clinical trials remain the only way we evaluate and ultimately approve new therapies for patients with cancer.

NCIs Mooney believes some good may come from adjustments made to ensure the safety of patients participating in studies and medical staff. But its still a work in progress, as hotspots rise and fall.

I think were learning more as we go along, she said. Some of the adaptations weve made have made all of us realize that perhaps there is better use we can make of technology telemedicine or technologies like that to take care of the patient. Thats a benefit to everyone, and they may be things that we can continue into the future once the public health emergency, as we all hope, has been resolved.

At Dana-Farber, Howley is enrolled in a Phase 1 trial of REGN4018, a bispecific antibody developed by the biotech company Regeneron. It grabs onto cancer cells at two points connected by a bridge. One side targets MUC16, a gene mutated in ovarian cancer and previously known as CA125 (which is still the name for the biomarker measured in diagnostic blood tests). The other side of the antibody binds to a T cell receptor that can then kill the cancer cell, the theory goes.

You realize this [Covid-19] is temporary and one day we will be back. For me, its like, I dont know how long I have.

When patients are hospitalized at the outset of the trial, which at this early phase is designed to test safety and dosing, its not an easy time for them with or without a pandemic. They are waiting for the drug to provoke their immune systems into killing their cancers. Howley felt savage pain across her abdomen and the wrath of a cytokine storm, the massive inflammatory response that also occurs in some Covid-19 patients whose immune systems go into overdrive.

We believe that the best antibodies you can get are the specific antibodies that travel to the sites of tumors. And thats what causes the abdominal pain, Matulonis, her oncologist, said.

From the beginning, Howleys treatment path has not been easy. After initial surgery to remove her tumor, she endured peritoneal delivery of the chemotherapy drug cisplatin directly to her abdomen, which was both painful and ultimately ineffective. She went on a standard drug called Doxil, but her cancer still progressed. Next she started a clinical trial that combined three drugs: one immunotherapy drug, one drug that blocks new blood vessel growth, and one PARP inhibitor that interferes with how cancer cells repair DNA damage. It was an aggressive regimen designed to expose the cancer to three agents it had never seen before, Matulonis said.

But one drug caused a bowel perforation, a known side effect. She continued to take the immunotherapy and the PARP inhibitor, but by November her cancer was progressing, measured by blood tests gauging her CA125 levels and imaging scans that spot metastasis.

The new trial, of the bispecific antibody, started in February.

I think for her, Ive always wanted to go beyond standard chemotherapy, Matulonis said. You can see that the tumor was a harder nut to crack. We really have to think outside the box to treat her.

Matulonis said Howley can stay on the current trial as long as she meets three conditions: She is benefiting from the drug, she is not having any significant toxicities, and she wants to continue. Howleys CA125 has hit four figures in the past. Before last weeks blood test, her last reading was 499. She was both nervous and eager to know the latest, though she tries not to put too much stock in the biomarker. The reading can vary with inflammation and the drug she is on causes inflammation, irritating one hip so much that she wants to ask if a cortisone shot would be allowed under the trials rules.

Except for the cancer, shell tell you shes healthy, and Matulonis agrees. Retired now from a career in client services, she lives with her husband in Sudbury, Mass., about a 40-minute drive to Boston. She walks three miles every morning, and she just got back to playing tennis. She ran the Falmouth Road Race last summer, astonishing a research nurse on her medical team who was volunteering on the sidelines.

For her visit last week, she wore a white, cowl-necked knit top port-friendly for blood draws and drug infusions through an opening high on her chest. Her lively blue eyes were set off by sparkly deep-blue eye shadow, her dark hair accented with blond highlights. Shes been the woman in the waiting room with no hair or eyebrows and knows how it feels when people look at you. Now she jokes about reluctantly giving up her fashion-coordinated cloth face mask for the fresh paper one Dana-Farber offers each patient upon check-in.

Howley has dual motivations for participating in cancer research. One is to help other women with ovarian cancer. Hopefully Im a piece of that puzzle thats going to give them a little insight, she said. They might have something here thats going to be so critical down the road for others.

Her other driving force is her 29-year-old daughter. She doesnt worry about their sharing BRCA1 or BRCA2 mutations her genetic tests were negative for those mutations but she is concerned about being a role model.

So much of my determination is just really providing an example to her, she said. Im not saying Ive got it down at all, but I try very hard to show her how to do it kind of gracefully. It doesnt mean Im going to do it. But I still try.

Cancer has already narrowed how she thinks about the future. Six months is as far out as shell plan these days, and Covid-19 has cramped her dreams of traveling to one of her favorite places, Marco Island in Florida. You realize this [Covid-19] is temporary and one day we will be back, Howley said. For me, its like, I dont know how long I have.

No one can tell her that, but she looks to Matulonis to see if her new CA125 number matches how good shes felt, even if she hit lousy on the tennis court.

The number is still moving in the right direction, Matulonis tells her: 259, down from 499 a month ago. That could mean her cancer burden is diminishing, Matulonis said, but cautioned that imaging scans will have to confirm it.

Howley knows that.

If it goes up 50 points, it doesnt necessarily mean anything. But at the same time, Im just blown away, she said. Today, its almost surreal to me, its going to take me a while to digest.

She is still elated as she climbs into the infusion chair for her next dose of the trial drug.

Maybe I better plan that trip.

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Cancer patients and doctors carry on with clinical trials during Covid-19 - STAT

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