Prevention and Treatment of Side Effects Clinical Trials

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Clinical Trial Conversations
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Clinical trials are critical to finding a cure for colorectal cancer. As an advocacy organization dedicated to supporting and empowering a community of patients, caregivers and families, Fight CRC has partnered with COLONTOWN to deliver a monthly blog series highlighting everything patients need to know about clinical trials and the best treatment options available.

In this series, we hope to cover promising trials that are enrolling, lessons learned from past research, logistics and resources to joining a clinical trial, and provide relevant and timely updates for our colon and rectal cancer community.

Clinical Trials Focused on Prevention and Treatment of Side Effects

July brings fireworks, barbecues, and super hot summer weather. In this month’s Clinical Trial Conversations blog post, Maia and Manju discuss prevention and treatment of side effects – specifically skin rash, hand-and-foot skin reaction syndrome, and peripheral neuropathy – which may occur in part or in full during colorectal cancer treatment. 

While the hotter weather may be a welcome relief to some patients’ and survivors’ physical discomfort from cooler or colder months, other patients and survivors may experience heat intolerance. Let’s not forget those patients experiencing skin-related side effects or syndromes, no matter the weather or season we are in. 

When your medical team is exceptionally focused on lifesaving treatment, discussions about side effects may not be forefront in their minds, and side effects may not be at the top of your list of questions either – until you begin to experience pain and discomfort, which you may think is a part of the treatment process that you have to “suffer through.” 

Since treatment effects vary among individuals, we don’t have a one-size-fits-all solution for everyone. However, we have put together a list of interesting clinical trials addressing skin rash, hand-and-foot syndrome, and peripheral neuropathy, which we hope will alleviate or help minimize side effects.

Prevention or treatment of skin rash from EGFR inhibitors (cetuximab, panitumumab)

Skin Rash Study Before Chemotherapy in Colorectal & Head and Neck Cancer Patients: NCT01874860

The purpose of this 100 person (50 people each, composing two treatment study arms: extensive treatment group (ETG) and standard of care group (SCG)) study is to find out if using preventive treatments, such as doxycycline (an antibiotic) capsules, sunscreen with SPF 30, hydrocortisone 1% cream, and a moisturizer will help to reduce the incidence and severity of the skin rash associated with cetuximab (Erbitux®) when compared to receiving standard of care for the treatment of skin rash.

Participants will start taking the capsule and applying the creams three days prior to beginning cetuximab therapy. They will continue this regimen for eight weeks. If patients develop severe skin rash as a result of cetuximab therapy, the study doctor may decide to reduce the amount of the dose of cetuximab that participants receive, or the study doctor may prescribe other medicines according to standard treatment recommendations, just as the study doctor would do if patients were not participating in this study. Participants in both arms will be monitored at enrollment, three weeks into cetuximab treatment, and at the end of cetuximab treatment for adherence, side effects, and quality of life. 

If participants in the SCG develop a severe skin rash, the study doctor will treat the participant’s rash according to standard treatment recommendations, which may include hydrocortisone 1% cream, doxycycline capsules, or other medications. There will be a follow-up period for both the ETG and SCG at the end of the subject's eight-week study treatment period, and at six months, 12 months, 18 months, and 24 months (participants will be contacted by telephone or this will be discussed during their routine clinic visit).

Study doctors will look at the incidence of cetuximab-induced rash, and compare the severity of cetuximab-induced rash between the ETG and the SCG. Quality of life, whether people follow the treatment regimen, and progression-free survival at specific time points will also be studied. Patients who have been previously treated with cetuximab or who are currently on tyrosine kinase inhibitors will be excluded from this clinical trial.

Efficacy and safety of two strengths of LUT014 Gel topically applied once a day for four weeks: NCT04759664

This 117 participant Phase II randomized study looks at the efficacy and safety of two strengths of LUT014 Gel applied on the skin once a day for four weeks, compared to a placebo, in metastatic colorectal cancer (mCRC) patients who developed Grade 2 EGFRI induced skin side effects.

Study doctors will look at the proportion of people in each treatment group who reached treatment success at four weeks. Treatment success is defined as an improvement (decrease) of at least one grade in the severity of the skin side effects from baseline to Day 28, based on a grading scale or answers in a questionnaire. The inclusion/exclusion criteria are listed on clinicaltrials.gov. People with beards cannot participate in the study as the beard could interfere with scoring of lesions. This trial is open and recruiting at 12 locations in the U.S.

Prevention or treatment of hand-and-foot syndrome from regorafenib (Stivarga®)

A Study to Investigate OQL011 on VEGFR Inhibitor-Associated Hand-Foot Skin Reaction in Cancer Patients (NOVA-II): NCT04088318

Hand-Foot Skin Reaction (HFSR) is a common side effect induced by Vascular Endothelial Growth Receptor Inhibitor (VEGFRi) treatment in cancer patients. The main purpose of this 112 participant, randomized Phase II study is to evaluate the safety and efficacy of OQL011 compared to vehicle ointment in treating patients with moderate to severe VEGFRi-associated HFSR. 

This study will also identify an optimal dosage for Phase III study and explore the pharmacokinetics profile of OQL011 in HFSR patients. Three doses of the ointment or vehicle will be applied on the skin, three times a day for up to six weeks. The primary outcome is to measure the proportion of patients who achieve NCI CTCAE v5.0 – Palmar-Plantar Erythrodysesthesia (PPE) grade 0 or 1. The trial is open and enrolling at 15 locations in the U.S.

Topical Tazarotene Vs Placebo In Hand-Foot-Skin Reactions: NCT04071756 

This randomized 70 participant Phase II clinical trial is studying the preventive use of topical 0.1% tazarotene gel daily, in addition to best practice standards to reduce the development of hand-foot skin reaction (HFSR). In this research study, the investigators are aiming to determine if the use of tazarotene gel daily, in addition to best practice standards: 

1) reduces the development of HFSR, 

2) decreases modification of regorafenib dose due to HFSR, 

3) improves health-related quality of life associated with HFSR, and 

4) decreases stress associated with HFSR. 

The primary outcomes of the study include the proportion of patients in each arm who develop grade-2 or higher HFSR within the first 8 weeks of protocol therapy, as well the proportion of patients who develop HFSR of any grade in each arm as measured by examination by a dermatologist.

Prevention or treatment of peripheral neuropathy from oxaliplatin

While some trials test a medicine for the first time, others use already-approved drugs in a new way. This is the case of the following two studies NCT04137107 and NCT04164069

Duloxetine to Prevent Oxaliplatin-Induced Peripheral Neuropathy in Patients With Stage II-III Colorectal Cancer: NCT04137107

This clinical trial is a Phase II/III trial for patients with stage II or stage III colorectal cancer who are receiving oxaliplatin (part of the Folfox chemotherapy combination), and who do not have peripheral neuropathy.

As an addition to their standard of care treatment, patients will be randomly assigned to receive either duloxetine or placebo. To prevent bias, (predisposition to interpret information in a particular way) neither the patients nor the investigators know which arm of the trial they are assigned. Duloxetine (Cymbalta) is an approved antidepressant medication that increases the amount of certain chemicals in the brain that help relieve depression and pain. This study aims to determine the best dose of duloxetine and how well it works in preventing the pain, tingling, and numbness caused by treatment with oxaliplatin.

This trial by the Alliance for Clinical Trials in Oncology is ongoing at more than 570 locations around the country.

Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab: NCT04164069 

This is also a trial that uses an approved drug in addition to standard of care. All stage II, stage III or stage IV colorectal cancer patients who are receiving standard of care chemotherapy (Folfox, with or without Avastin®) will also take a pill, dasatinib (Sprycel®).

Dasatinib is a tyrosine kinase inhibitor used for the treatment of lymphoblastic or chronic myeloid leukemia with resistance or intolerance to prior therapy. It blocks the action of an abnormal protein that signals cancer cells to multiply. The researchers’ hypothesis, based on preclinical evidence, is that blocking these enzymes may reduce oxaliplatin-induced peripheral neuropathy. To test that, patients will receive an oral dose of dasatinib, intermittently ( taken only some days on the chemo cycles).

In contrast to the first trial, this trial is a small, 10 patients study, taking place only at Ohio State University Cancer Center (Columbus).

Assess Safety and Tolerability of ART-123 + FOLFOX + Bevacizumab in Metastatic Colorectal Cancer Patients: NCT05251727

This trial, on the other hand, is one that tests a medicine for the first time. This trial is only for metastatic (stage IV) colorectal patients who are receiving oxaliplatin and bevacizumab (Avastin®).

To test how well it works to prevent peripheral neuropathy, some patients will receive a novel, experimental agent (ART-123, a thrombomodulin alfa drug) as an infusion during the chemotherapy session, while other patients will receive a placebo.

The trial started this year, and it is ongoing at several locations in the U.S. and Japan.

Prevention of Oxaliplatin-induced Nerve Damage in the Body's Extremities (OxaNeuro): NCT05404230 

This trial is not yet recruiting (as of July 2022) and will take place at a university hospital in Denmark. 

It is also a clinical trial for colorectal patients who are going to receive oxaliplatin-containing therapy, who have not started yet, nor have peripheral neuropathy at the present.

However, the study does not test a novel drug or an already-approved one. It proposes something that could be considered a dietary intervention: the addition of a high dosage of n-3 PUFA (polyunsaturated fatty acids), by taking fish oil capsules while receiving Folfox.

The purpose of this study is explore if high dosage of n-3 PUFA (fish oil capsules, 3 grams per day for eight months) reduces the incidence and severity of chemotherapy-induced peripheral neuropathy (CIPN) eight months after adjuvant oxaliplatin, following surgery for high-risk colorectal cancer. Some patients will take fish oil capsules, while patients in the placebo arm will take n-6 polyunsaturated fatty acids capsules (corn oil, 2 grams per day, the equivalent of adding an extra spoon of food oil while cooking).

Effect of Hemp-CBD on Patients With CIPN (Coala-T-CBD): NCT04398446

This trial is different from all the clinical trials listed above. This study is for stage II and stage III colorectal patients who have already developed peripheral neuropathy, after receiving chemotherapy that included oxaliplatin. In other words, this trial is for survivors who are not currently receiving treatment but are dealing with the aftermath of peripheral neuropathy.

In this small trial, taking place only in Pennsylvania (Wynnewood), patients take hemp-based cannabidiol (CBD) tablets (or placebo) for three months.

Cannabis comprises tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD is not psychoactive and does not appear to be addictive. One specific form of CBD is approved as a drug in the U.S. for seizures. Studies specifically looking at the role of CBD in chemotherapy-induced neurotoxicity have shown a neuroprotective effect of CBD in mouse models. Studies have demonstrated that a 14-day dosing regimen of CBD prevented the onset of paclitaxel-induced mechanical and thermal sensitivity.

These intriguing results suggest that cannabinoid agents could potentially reduce the severity and duration of chemotherapy-induced peripheral neuropathy for patients.

Additional colorectal cancer clinical trials resources and information

For more Fight Colorectal Cancer information and resources, check out our Side Effects Mini Magazine, CIPN (chemotherapy-induced peripheral neuropathy) podcast, and CIPN webinar

Stirvarga® also provides resources on managing side effects, which contains specific information for skin rash from EGFRi and for hand-foot skin reaction.

Stay Tuned for More Colorectal Cancer Clinical Trials Conversations!

Once a month, Maia and Manju will spend time unpacking important research trials, tips, and advice for our community. Be sure to subscribe to sign up with Fight CRC and join COLONTOWN’s online community to continue receiving the most relevant updates in the CRC world!

You can also follow Maia (@sassycell) and Manju (@manjuggm) to stay updated on research and trials and visit ClinicalTrials.gov for more information on trials.

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