Get insights on how to make finding blood cancer clinical trials easier in this free ebook!

You’ll learn:

  • Find treatment options for various types of blood cancers.
  • Get comprehensive lists of clinical trials available.
  • See the most current clinical trials and their criteria.
  • Learn the ins and outs of preparing ahead of time to make finding a trial easier.
  • Get an inside look at how digital records organization is streamlining the clinical trial process.
  • Find ways to make it easier for you to support yourself and get support from those around you.

Excerpt

Every pancreatic cancer treatment available today was approved through clinical trials. Such ongoing research is essential to resolving critical issues regarding pancreatic cancer, including the following:

  • Developing methods to diagnose pancreatic cancer earlier in contrast to the current state, when most patients have locally advanced or metastatic disease at initial diagnosis
  • Providing effective therapies before surgery to increase the number of patients who are eligible for surgery
  • Developing new treatment approaches

Scientific Benefits of Clinical Trials

After researchers have successfully studied a new cancer therapy with required laboratory and animal studies, investigators develop a clinical trial protocol to begin testing in people to evaluate the agent’s safety and efficacy. Such testing is required by the Food and Drug Administration (FDA) before a cancer drug is approved for use by the public.

Therefore, the clinical trial process plays a crucial role in advancing our scientific progress. Understanding the following is necessary to develop novel agents, treatment combinations, and methods that may lead to enhanced outcomes for pancreatic cancer patients:

  • The molecular mechanisms regarding how cancer cells develop, proliferate, and spread
  • How the surroundings of the tumor, called the microenvironment, affect the development and proliferation of cancer cells
  • An increased understanding of tumor biology that leads to the development of novel therapies to target specific genetic mutations, chromosomal rearrangements, and other abnormalities in cancer cells and/or to enhance the body’s immune response to cancer

What Are the Barriers to Clinical Trial Participation?

It has repeatedly been estimated that less than 5% of adult cancer patients who are eligible for clinical trials actually participate. Multiple studies have identified barriers that may prevent cancer patients from enrolling in clinical trials.

First, after receiving a cancer diagnosis, patients often don’t know what questions to ask and where to begin to get more information. Some assume that it will be easy to obtain their records and that these records are kept indefinitely. Others become overwhelmed by the simple thought of trying to obtain their medical records at all. Furthermore, a patient’s physicians may use different electronic health records (EHRs) and won’t have electronic access to all patient records from other providers. 

As a result, pancreatic cancer patients, most of whom see multiple specialists, may have tremendous difficulty obtaining all their records, potentially causing repeat testing, increased potential harms (e.g., with repeated imaging), and diagnosis and treatment delays that could greatly impact therapeutic efficacy and increase risk of cancer recurrence. Yet, some pancreatic cancer patients may not realize the importance of obtaining their medical records to provide multiple specifics regarding their pancreatic cancer type that are crucial in determining appropriate standard treatments and clinical trial eligibility.

The Importance of Obtaining All Your Medical Records

Pancreatic cancer patients will need to obtain their full medical records to be fully informed about optimal treatment options, obtain second opinions, and provide all necessary information to clinical trial teams to determine which trials may be appropriate. Fortunately, pancreatic cancer patients can contact Ciitizen, an online platform and service that was established specifically to assist patients in obtaining all their medical records for free. Ciitizen will provide the medical records digitally, helping patients keep their records organized and updated.

What Key Information Should Be Included in Your Medical Records?

Your medical records should include information regarding the following.

Type of Pancreatic Cancer

There are two primary types of pancreatic cancer in which abnormal changes in DNA, the carrier of genetic information, cause certain pancreatic cells to develop, divide, and proliferate uncontrollably:

  • One cancer develops within the pancreatic exocrine cells, which produce, store, secrete, and transport key digestive enzymes and release them into the narrow channels called pancreatic ducts. The digestive enzymes then pass into the first part of the small intestine (duodenum), where they are activated to assist in food digestion. Called pancreatic ductal adenocarcinomas (PDACs), these represent 90% to 93% of pancreatic cancers. Therefore, if you see just the term, “pancreatic cancer,” this typically refers to an exocrine pancreatic cancer. 
  • One cancer arises in pancreatic endocrine cells that produce hormones, such as insulin to help control blood sugar levels. Known as pancreatic neuroendocrine tumors (PNETs) or islet cell tumors, approximately 50% of PNETs are classified as “functional,” meaning that they produce excess hormones, resulting in various symptoms depending on the specific hormone type. In contrast, non-functioning PNETs do not produce enough excess hormones to lead to any associated symptoms. 

Specific Cancer Subtype 

If you have been diagnosed with a PNET, it’s important to know your specific PNET type, which is based on and named for the specific hormone that they produce. These include the following:

  • Insulinomas
  • Glucagonomas, which may produce excessive levels of the hormone glucagon, balancing the effect of insulin by regulating blood sugar
  • GRFomas, which produce excess levels of the growth hormone release factor (GRF) that in turn, stimulates growth hormone production, resulting in abnormal enlargement of the head, arms, and legs (acromegaly)
  • Somatostatinomas
  • ACTHomas
  • VIPomas

Whether the PNET Is Functional

About half of PNETs are categorized as “functional,” causing the pancreas to overproduce specific hormones, leading to hormone-related symptoms. Non-functional PNETs do not produce excess hormones, and therefore, they do not result in hormone-related symptoms. Subsequently, non-functional PNETs are usually diagnosed once they have become advanced and begin to cause non-specific symptoms, such as jaundice or pain, due to pressure on nearby organs.

Pancreatic Cancer Stage

With solid tumors, such as pancreatic cancer, a staging system is used to indicate tumor size, whether it is locally advanced or whether it has spread to distant sites in the body (metastasized), all of which are crucial factors in determining how serious the cancer is and optimal treatments. PDACs and PNETs are staged using different staging systems. However, they both use the American Joint Committee on Cancer (AJCC)’s: “TNM” system: 

  • T = Tumor: size and extent of the primary tumor
  • N = Lymph Nodes: spread to nearby lymph nodes
  • M = Metastases: spread to distant organs

For PDACs, staging ranges from stage 0 (carcinoma in situ) to stage IV. PNET stages range from stage I to IV. The lower the stage number, the less pancreatic cancer has spread. Stage IV designates an advanced cancer that has spread to distant sites (M1), such as the liver; may be of any size and may or may not have spread outside the pancreas (Any T); and may or may not have spread to regional lymph nodes (Any N).

Pancreatic Tumor Grade

Tumor grade indicates how closely cancer cells resemble normal tissue beneath a microscope:

  • Low-grade (G1): closely resemble normal tissue
  • Medium-grade (G2): appear somewhat abnormal
  • High-grade (G3): appear extremely abnormal

Low-grade cancers tend to grow and proliferate more slowly than high-grade cancers, the latter of which has a poor prognosis compared to G1 and G2 tumors.

For PNETs, a key factor in grading is assessing the number of cells that are currently dividing into new malignant cells based on the following:

  • Mitotic count: measures the number of cells seen microscopically that are dividing into two new cells (mitosis)
  • Ki-67 index: measures the portion of cells that are nearly ready to begin dividing

Based on these factors, PNETs can be further classified into well-differentiated and poorly differentiated cancers. Well-differentiated PNETs are low-grade and intermediate-grade tumors with <20 mitoses and a Ki-67 index of <20%. Poorly differentiated or high-grade tumors have >20 mitoses or a Ki-67 index of >20% and frequently grow and spread aggressively.

Tumor Resectability

While the AJCC staging system provides specific classifications based on the extent of cancer spread, physicians may use a simpler staging system based on whether the pancreatic tumor can be completely removed (resected) surgically. The National Comprehensive Cancer Network (NCCN) has provided guidelines on resectability for PDACs. But research has shown that the same criteria may be successfully applied to select patients with PNETs who meet the NCCN’s borderline resectable criteria for PDACs:

  • Resectable (R0): The cancer is confined to the pancreas or has just spread beyond it, and it appears that the entire tumor can be surgically removed.
  • Borderline resectable (R1): The tumor may have just reached regional blood vessels, yet it may potentially be entirely removed surgically.
  • Unresectable (R2): The tumor cannot be removed completely with surgery because it has grown into or been surrounded by major blood vessels (locally advanced) or has metastasized to distant organs. Surgery may still be conducted to help prevent or relieve symptoms (palliative care), such as intestinal or bile duct blockage.

In some cases, although imaging tests may have suggested that a pancreatic tumor is resectable, it may become apparent during surgery that it’s not possible to entirely remove the tumor. In such cases, some cancer may be removed if a biopsy hasn’t already been performed, but the rest of the surgery will no longer take place to help prevent potentially severe adverse effects.

Results of Genetic Testing and Molecular Tumor Profiling

The Pancreatic Cancer Action Network (PanCAN) strongly advises that all pancreatic cancer patients undergo genetic testing and tumor molecular profiling to identify any targetable mutations, regardless of whether they have a family history of pancreatic cancer or other cancer types and abnormalities. Genetic (germline) testing assesses a patient’s blood or saliva for inherited genetic mutations that may be associated with familial pancreatic cancer. 

During tumor molecular profiling (also known as genomic or biomarker testing), tumor tissue obtained during a biopsy is evaluated for specific mutations or other abnormal changes in the patient’s pancreatic malignant cells. The NCCN and the American Society of Clinical Oncology (ASCO) also updated their guidelines recommending such testing for pancreatic cancer patients.

Mutations known to be associated with PDACs or PNETs may not only be inherited but may also occur spontaneously (sporadically) in some cases. For example, recent research suggests that genetic mutations may occur at a similar rate in PDAC patients regardless of family history, such as mutations of the BRCA1, BRCA2, CDKN2A, MLH1, TP53, or ATM genes. Regarding PNETs, although most such mutations develop sporadically, they can also develop secondary to inherited familial syndromes in approximately 9% of cases. This most commonly occurs in familial multiple endocrine neoplasia type 1 (MEN1), a hereditary disorder characterized by multiple tumors of the endocrine glands. Yet, it may also be seen with other familial syndromes, such as von Hippel-Lindau disease, which is associated with the development of tumors and cysts in multiple organs.

Mutation of the MEN1 gene is also the most frequently mutated gene in sporadic PNETs. Additional sporadic mutations associated with PNETs include mutations of DAXX or ATRX; certain genes in the mTOR pathway, including ITSC 2, PTEN, and PI3KCA; and TP53. Researchers found that when PNET was associated with MEN1, DAXX, or ATRX mutations, patients had improved outcomes, living about ten years after diagnosis. Furthermore, there are currently available therapies that target the mTOR pathway, suggesting that these may be effective treatment options for certain PNET patients, although additional clinical trials are needed to determine efficacy in such cases. (The mTOR pathway, which is often dysregulated in cancers, is a central regulator of cell physiology, metabolism, development, proliferation, and survival.)

Cancer Screening for Familial Pancreatic Cancer

Do you or anyone you know have the following?

  • Two or more first-degree relatives affected by pancreatic cancer
  • A first-degree relative with pancreatic cancer before fifty years of age
  • A familial genetic syndrome associated with pancreatic cancer

If so, this may suggest an increased risk of familial pancreatic cancer and the need for a consultation with a genetic counselor to determine whether you should consider participating in a pancreatic cancer screening program. Please note that PanCAN has a Know Your Tumor® precision medicine service that provides information on germline (familial) and somatic (sporadic) mutations to patients, family members, and their healthcare teams.

Additional Barriers to Clinical Trial Participation

Now that we’ve discussed the importance of obtaining your medical records, we shall cover several additional barriers that may prevent patients from participating in clinical trials—and ways that you can overcome these barriers.

  • In many cases, oncologists do not provide information to cancer patients regarding available clinical trials. But many cancer patients say that they’d be interested in participating if they’d been told about such trials. The important takeaway is to proactively ask your oncologist or other members of your healthcare team if they’re aware of any pancreatic cancer clinical trials for which you’d be a good fit. 
  • However, since there are so many ongoing and newly recruiting oncology clinical trials, note that it’s difficult for even the most informed oncologists to be aware of all clinical trials for pancreatic cancer, particularly those conducted outside their own institutions. Therefore, you must search for clinical trials using online platforms and services that help match you to proper trials. But before doing so, remember the importance of obtaining all your medical records to have key information concerning your pancreatic cancer.
  • You may find that some clinical trials have overly restrictive eligibility criteria, resulting in the potential exclusion of certain patient populations, including patients with certain comorbidities (e.g., diabetes, cardiovascular disease); prior treatments; or in some cases, those with metastatic disease. However, ASCO and the FDA are stressing the need for investigators to carefully assess eligibility criteria to prevent overly specific, restrictive criteria. In addition, more researchers overall are recognizing that traditional eligibility criteria may be too restrictive and an unnecessary barrier to many patients who are eager to participate in clinical trials and lead to trial results that may not be generalizable to real-world patients. 
  • Specifically, regarding patients with uncontrolled pancreatic cancer that is resistant to treatment (refractory), clinical trial design must allow for timely patient enrollment before clinical deterioration and decline in functional status. (Trial designs must account for the limited time during which these patients may be able to maintain an Eastern Cooperative Oncology Group performance status of 0 to 1, which is generally required to enroll in a treatment clinical trial. 
  • Due to potentially rapid deterioration in refractory, uncontrolled pancreatic cancer, patients may be reluctant to participate in clinical trials due to concerns regarding the possibility of prolonged wait times before beginning study visits. Innovative phase I adaptive trial designs that reduce study duration while prioritizing patient safety and interpretability of results may help reduce wait times for patient trial slots. In addition, if possible, the required “wash-out periods” during which no treatment is given before beginning a trial treatment must not be too lengthy (i.e., less than twenty-eight days). Although such clinical barriers are due to the natural history and prognostic factors impacting some patients with refractory pancreatic cancer, an increasing number of investigators are dedicated to establishing innovative trial designs and less restrictive eligibility criteria to help overcome such barriers.

Common Misconceptions and the Realities

There are several common misconceptions regarding clinical trials that may cause patients to be wary of participating in studies. However, it’s crucial to demystify such myths by sharing the realities.

  • Misconception: I can only participate in a clinical trial if I have no other standard treatment options.
    • Reality: This is an extremely common misconception about clinical trials. But for patients with pancreatic cancer (and several other cancers), it’s often appropriate or even preferable for you to consider clinical trial options before or early in your treatment, even in cases where standard-of-care options are available. Clinical trials may also be good options if the current standard therapy hasn’t been effective or there is not a reliable standard of care and the treatments received to date haven’t produced positive outcomes. As an example, you may fit the inclusion criteria for a trial where a novel agent is added to a standard therapy to assess whether there is increased efficacy.
  • Misconception: I’ll receive a placebo (inactive agent) rather than the investigational agent.
    • Reality: You’ll be taken through an informed consent (IC) process, during which a study coordinator will provide you with and carefully review an IC document. The coordinator will answer any questions that you may have to ensure that you understand the purpose of and what will take place during the trial. Your IC will outline whether it’s possible that some participants may receive a placebo. That said, oncology trials rarely use placebos and will always provide active treatment. Rather, oncology trials may be designed that compare standard therapy plus placebo against standard treatment plus a new treatment, so it is reasonable and ethical for cancer patients to be placed in either treatment group.
  • Misconception: I can’t receive a standard-of-care treatment if I want to participate in a clinical trial.
    • Reality: Cancer clinical trials often include standard-of-care treatments. Again, the standard therapy may be given with a novel therapy or a placebo to determine whether the new agent improves response without introducing bias into the trial. In addition, there are other trial types, where you’ll continue to receive standard of care for your cancer type and regularly be asked to respond to questionnaires to evaluate quality-of-life measures or patient-reported outcomes.
  • Misconception: Once the clinical trial is over, I’ll no longer have access to the investigational agent even if the treatment is safe and effective.
    • Reality: Many trials are designed such that those who are participating can continue treatment if they’re obtaining a beneficial response. If there is no significant evidence that continuing treatment with the agent is better than stopping it, the drug may be discontinued after the participant has received the prescribed course of treatment as outlined in the study protocol. Generally, the only situation in which a drug may be discontinued even if effective would be due to toxic adverse effects or safety issues.
  • Misconception: I’ll need to pay the costs of receiving therapy in a clinical trial because my insurance will not cover it.
    • Reality: In most cases, there is no direct cost to patients who participate in clinical trials. Private health insurance and Medicare usually cover routine care associated with clinical trials and tests, such as imaging and lab tests. The trial sponsor typically covers the costs of the investigational agents and any additional tests that would not have been required if the patient was receiving standard care outside of a trial, such as additional imaging tests other than those required for routine restaging. The Affordable Care Act (ACA) of 2010 mandated that most private health insurers cover routine care costs for participants in approved clinical trials. Most states also have clinical trial coverage laws mandating coverage of routine medical care associated with clinical trials, although the specifics vary from state to state. Importantly, however, there are limitations to such mandates. For example, health insurers aren’t required to cover clinical trial costs if conducted at an institution outside their plans’ provider networks unless the plan includes coverage for out-of-network care, which may have higher outside-network cost-sharing. Also, health insurance plans established prior to the ACA’s enactment date (before March 23, 2010) are grandfathered and therefore, are not required to change their plans to include coverage of clinical trial costs. That said, when such plans increase insured costs or decrease benefits, they lose their grandfathered status.

Financial Considerations as Potential Barriers

Although health insurance and clinical trial sponsors usually cover direct costs, many patients are concerned about how much their insurance will pay and any indirect or ancillary costs that they may incur should they participate in a trial. Therefore, when considering a trial, ask your study team the following questions:

  • Who will be paying for my routine cancer care during the clinical trial? Will Medicare or my private health insurance company cover these costs? 
  • What is the impact on what my insurance will cover if I have a Medicare Advantage Plan or am on Medicaid? 
  • Will you help me speak with my insurance company, Medicare, Medicare Advantage Plan, or Medicaid to determine what coverage I’ll have?
  • Can I participate in a clinical trial if I don’t have health insurance?
  • Are there any indirect, ancillary costs even if I do have health insurance? (For example, such ancillary costs may include transportation to and from study visits, lodging, meals, childcare, missed time from work, etc.) 
  • Will I receive any compensation for participating in the trial?
  • Will I be reimbursed for any of my ancillary costs (e.g., transportation, lodging, and meals)?

Again, be sure to speak with your clinical trial coordinator and your health insurance company before enrolling in a specific clinical trial. In addition, consider contacting PanCAN Patient Services to receive information about financial, health insurance, and transportation resources that may assist with additional costs.

Logistical Considerations

Ask your study team questions regarding logistics. Here are a few examples:

  • Where is the study site located? Is there another participating study site that is closer to me, requiring less travel?
  • How long will the trial last, and how many study visits will I need to make? Is it possible to conduct any of the trial visits remotely, such as via a telemedicine visit?
  • Will I need to obtain lodging for any study visits? If so, how often will that be the case?
  • What will take place during each study visit?
  • Do I need to undergo any testing or procedures during the study, such as lab tests, imaging studies, or biopsies? What are the specific tests and procedures, how often do they need to be conducted, and why are they necessary as part of the trial?
  • Who will be overseeing my cancer care during my participation in the trial?

General Considerations

You’ll also want to ask questions concerning the purpose, design, conduct, and results of the clinical trial:

  • What is the goal of this clinical trial?
  • Is it possible that I’ll receive a placebo in addition to standard therapy rather than the investigational therapy combined with standard of care?
  • If I do receive a placebo, can I receive the investigational therapy at the conclusion of the trial?
  • If I receive the investigational agent and respond well to treatment, can I continue to receive the treatment?
  • What previous research has been conducted on this investigational therapy?
  • Will I receive information regarding the results of this trial?

What Are the Benefits of Participating in Pancreatic Cancer Clinical Trials?

Due to what is often late diagnosis, the difficulty of diagnosis, and pancreatic cancer’s aggressiveness, PanCAN and several national guidelines strongly recommend that all pancreatic cancer patients consider participating in clinical trials at diagnosis and during every treatment decision, regardless of type or stage. This may give patients access to the best treatments currently available and to novel treatments that may be safer and more effective than standard of care. Additional benefits of participating in pancreatic cancer clinical trials include the following:

  • Many promising novel agents for pancreatic cancer may be available solely in clinical trials. 
  • Even if you don’t benefit personally from a specific treatment under study, your participation will be crucial in helping investigators to learn more about successfully treating these aggressive cancers, enabling future cancer patients to receive improved treatment and adding to medical knowledge that will enhance medical care.
  • There are strict guidelines and rules in place to protect your safety and privacy if you give your consent to participate in a clinical trial.
  • It’s possible that you’ll receive a novel agent that is more effective with potentially fewer adverse effects compared to the standard of care.
  • You may be followed more closely and have more frequent medical care visits during your treatment as part of a clinical trial. The progress of your treatment will be carefully monitored.
  • You’ll be playing a more active role in your treatment, learn more about your type of pancreatic cancer, and essentially become a member of your own healthcare team.
  • Since you’ll be seen more frequently, you’ll have additional opportunities to ask questions about your cancer and your ongoing care from a research team of physicians and other healthcare providers who have expertise regarding your type of pancreatic cancer and its treatment.
  • You may learn about additional supportive resources for patients with your pancreatic cancer type.

Searching for Pancreatic Cancer Clinical Trials

Several organizations can conduct clinical trial searches on your behalf, matching you to appropriate trials, and/or provide clinical trial search platforms where you can search on key terms regarding your specific pancreatic cancer type. 

When you receive your medical records, review the different terms used to describe your specific type of pancreatic cancer to help you narrow down your search results to trials appropriate for you. For example, if you have a PNET, you can search for “pancreatic neuroendocrine tumor,” “islet cell tumor,” the specific PNET subtype (e.g., “insulinoma”; “insulinoma, malignant”), “pancreatic neuroendocrine tumor, G1” (or G2 or G3). For PDAC, you can search for “pancreatic adenocarcinoma,” “pancreatic adenocarcinoma resectable,” “pancreatic adenocarcinoma stage III,” pancreatic adenocarcinoma non-resectable,” etc. You can also search by specific treatments, genetic mutations associated with PDACs or PNETs, “familial pancreatic cancer,” inherited conditions associated with PNETs (e.g., MEN1), trial phase, and location.

Organizations that may conduct clinical trial searches for you and provide clinical trial search platforms include the following:

  • Ciitizen has a clinical trial matching service.
  • You can use PanCAN’s Case Managers and Clinical Trial Finder to request further information regarding the results of a clinical trial search.
  • The National Cancer Institute (NCI)’s Cancer Information Service offers free tailored clinical trial searches for NCI-supported trials, the results of which you can discuss with your oncologist and healthcare team. You can reach them at (800) 422-6237 or (800)-4-CANCER, and select option 2. You can also contact them via a Live Chat or email. These services are available in English and Spanish.
  • Many major medical centers also have clinical trial finders on their websites that you can search by various keywords to locate appropriate clinical trials. Consider visiting websites of any medical centers that may be close to you. For example, if you live in Connecticut, you may wish to search Yale’s clinical trial finder to identify any new clinical trials for pancreatic cancer. Although not an all-inclusive list, major medical centers with clinical trial finders include the following:
  • There are also several pancreatic cancer registries and initiatives:
    • MSKCC’s Pancreatic Tumor Registry includes both patients with pancreatic cancer and people with a strong family history to help investigate inherited risk factors and environmental factors that may lead to the development of pancreatic cancer. 
    • PanCAN’s Patient Registry is a global online registry established to identify patterns in treatment, diagnostics, and side effect management that may lead to improved treatment options and patient outcomes. 
    • MD Anderson Cancer Center has launched its Pancreatic Cancer Moon Shot® initiative to focus research on critical issues facing pancreatic cancer patients, including developing new treatment strategies, designing methods to diagnose pancreatic cancer earlier, and enhancing outcomes by providing therapy before surgery.

Ciitizen is a free service that helps patients get more out of their health records. Our platform enables patients to find better treatment options and gives them the opportunity to advance the research for cures.

Ready to get your medical records in order? Get started today!