Este mes, hablamos con Maia y Manju sobre los ensayos clínicos para pacientes con cáncer colorrectal (CCR) en estadio II o III.

¿Por qué es importante que los pacientes con CCR en estadios tempranos empiecen a buscar ensayos?

Manju: Muy buena pregunta. Puede haber nuevos avances en el campo que se estén probando a través de ensayos clínicos a los que los pacientes en fase inicial sólo puedan acceder a través de ensayos, como nuevos enfoques para tratar el cáncer de recto, por ejemplo, o ensayos que analicen la utilidad clínica de ctADN. In many of these cases, early-stage patients would likely be randomized to get Standard of Care (SOC) treatments for their condition or that plus the experimental intervention. Early-stage CRC clinical trials allow patients as a group to have more treatment options. Maia, did I cover the important points?

Maia: Absolutely. Stages II and III patients receive surgery with curative intent, so it’s unlikely most patients and even doctors will think about clinical trials in those cases. However, as you said, a clinical trial may provide access to a cutting-edge technology (without compromising standard of care, of course), for example: a new surgical approach; a new way to dose chemotherapy, to maximize results while minimizing side effects; a non-invasive monitoring tool, like ctDNA; an immunotherapy to prevent recurrence.

¿Qué ensayos les entusiasman a ambos que las comunidades de las fases II y III deberían conocer?

Maia: Me gustaría destacar los ensayos clínicos que pretenden prevenir la recurrencia alistando al sistema inmunitario para esa tarea. Nuestro potente sistema inmunitario trabaja constantemente para reconocer y eliminar las células que tienen el ADN dañado y, por tanto, tienen potencial para convertirse en cancerosas. En ese sentido, el cáncer es una manifestación de un mal funcionamiento de la inmunidad. Mientras que la cirugía, la quimioterapia, la terapia dirigida y la radiación se dirigen al cáncer en sí, la inmunoterapia es una clase de tratamientos que funciona ayudando al sistema inmunitario a reconocer y atacar las células cancerosas, como se supone que debe hacer. De este modo, las inmunoterapias están proporcionando respuestas duraderas para muchos tipos de cáncer. 

En el caso de los pacientes con CCR, hay un tipo de inmunoterapia en fase de ensayo clínico para pacientes en fase inicial: las vacunas.

iNeST RO7198457 (Autogene cevumeran) es una vacuna personalizada contra el cáncer, basada en ARNm, que se administra por vía intravenosa durante 12 meses a pacientes con CCR en estadio II (alto riesgo) y estadio III cuya prueba de ctADN dio positivo tras la resección. En este juicioLos resultados de los pacientes que reciban la vacuna se compararán con los resultados de los pacientes que reciban el tratamiento estándar (enfoque de "espera vigilante").

Even if the vaccine is a novel agent, it is not totally unknown by now:  A juicio previo used this vaccine combined with other immunotherapy for treatment of stage IV patients. Even if the clinical response was low when trying to treat patients with active cancer, the researchers determined that the vaccine does generate tumor-specific immune responses, and it is safe. The vaccine may have a role when used to prevent recurrence, with no active disease, and this trial looks forward to answering that question and, hopefully, helping many patients to keep no evidence of disease (NED).

Ad5.F35-hGCC-PADRE is another vaccine being investigated in a ensayo clínico for many cancers, and that recruits stages I, II, III (and even stage IV with NED) CRC patients. This Guanylyl Cyclase C Vaccine is for prevention of recurrence, in patients treated with curative intent, who have NED following front-line therapy with surgery, radiation therapy, and/or chemotherapy. Thomas Jefferson University (Philadelphia, PA) has been researching and conducting other trials with this vaccine for years, so there is literature about its safety and efficacy.

Y hay más ensayos clínicos para pacientes en estadios II y III que pueden ayudar a evitar la recidiva y les beneficiarán al proporcionarles un seguimiento exhaustivo.

At risk of sounding like a broken record: There are clinical trials for every step in this journey, for those who think a clinical trial might be helpful. Clinical trials are not the last resource, nor do they always use completely unknown agents. Just keep on the loop: You or a loved one may be helped by a clinical trial.

Manju: I have been watching the early-stage CRC ctDNA space, and two trials are very interesting to me. There are many new trials coming up, so this is an exciting area to follow.

And there are more clinical trials for stages II and III patients that may help to avoid recurrence and will benefit them by providing thorough follow up watching the early-stage CRC ctDNA space, and two trials are very interesting to me. There are many new trials coming up, so this is an exciting area to follow.

The COBRA Trial for Stage II Colon Cancer (PI: Dr. Morris) is for early stage (IIa) colon cancer patients after curative intent surgery, for whom chemotherapy is not otherwise recommended. This trial has two arms: In arm one, patients receive standard follow-up as they would otherwise. They will have regular surveillance checkups including blood collection for ctDNA testing, but they won’t get any additional treatments.

In arm two, based on their ctDNA test when they enroll in the study, if ctDNA positive, their doctor will start them on the course of chemotherapy that is best for them. If their ctDNA test is negative, then they will get regular checkups including ctDNA tests for a period of three years while they are on the study.

And there are more clinical trials for stages II and III patients that may help to avoid recurrence and will benefit them by providing thorough follow up watching the early-stage CRC CtDNA space, and two trials are very interesting to me. There are many new trials coming that is best for them. If their CtDNA test is negative, then they will get regular checkups including ctDNA tests for a period of three years while they are on the study.

The Stand Up To Cancer ctDNA Trial (PI: Dr. Parikh) is for stage III colon cancer patients who have recently completed all their treatments. They get tested for ctDNA and if positive, they are randomized to 1) active surveillance, or 2)  be eligible based on their tumor characteristics, to receive either the next line of chemotherapy (FOLFIRI), or targeted therapy (if BRAF mutated or Her2 amplified), or immunotherapy if MSI-H. Los que den negativo en la prueba de ADNct se someterán a la vigilancia activa recomendada para los pacientes en estadio III. El objetivo del ensayo es averiguar si existen diferencias en la recurrencia del cáncer y en la salud entre los pacientes con ctADN positivo en vigilancia activa frente a más tratamientos, y cómo afectan más tratamientos a los niveles de ctADN. El ensayo ya está abierto en el Hospital General de Massachusetts, el Centro Oncológico Memorial Sloan Kettering, Cornell, el Instituto Oncológico Dana-Farber y Johns Hopkins.

These trials are very interesting to me because they can tell us whether detecting recurrence early via ctDNA positivity and treating early with chemotherapy (before things show up on a scan) affects the outcomes for patients with stages II and III colon cancer. Such trials are critical to assess the clinical utility of ctDNA testing.

Para obtener más información sobre los ensayos clínicos, consulte nuestro recursos and download the Fight CRC Clinical Trial brochure.

Fight CRC trabaja codo con codo con la comunidad de pacientes para descubrir nuevas formas de mejorar y prolongar la vida abordando cuestiones como éstas. Para que los ensayos clínicos beneficien a las poblaciones a las que van dirigidos, es necesario aumentar la diversidad racial y étnica entre los participantes.

Más información

Una vez al mes, Maia y Manju dedicarán tiempo a desgranar importantes ensayos de investigación, consejos y sugerencias para nuestra comunidad. No deje de suscribirse a inscríbete with Fight CRC and join COLONTOWN’s online community to continue receiving the most relevant updates in the CRC world!

También puede seguir a Maia (@sassycell) y Manju (@manjuggm) to stay updated on research and trials and visit ClinicalTrials.gov for more information on trials.

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