Regorafenib + Anti-EGFR Therapy for Colorectal Cancer

Not currently recruiting at 16 trial locations

Overseen By Benjamin A. Weinberg

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: Anti-arrhythmics

Disqualifiers: Heart failure, Hypertension, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 58

Duration: Variable, up to 20 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining regorafenib with anti-EGFR therapy (cetuximab or panitumumab) for treating colorectal cancer that cannot be surgically removed and has spread locally or to other parts of the body. The study examines the effects of taking regorafenib (a targeted cancer therapy) followed by cetuximab or panitumumab, and vice versa. Individuals with advanced or metastatic colorectal cancer who have not previously received these specific drugs might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on blood thinners like warfarin or heparin, you can still participate with close monitoring. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that regorafenib is FDA-approved for treating advanced colorectal cancer, indicating it has undergone safety testing in people. In earlier studies, regorafenib was generally well-tolerated, though some patients experienced side effects like tiredness and skin reactions on their hands and feet.

Cetuximab has also undergone extensive study. It is usually well-tolerated, but about 3% of patients experienced serious reactions during administration.

Panitumumab has been tested in several clinical trials. It appears generally safe, though some patients have experienced skin reactions and other side effects.

Irinotecan is effective but can cause severe side effects like diarrhea and low white blood cell counts, requiring close patient monitoring.

Overall, these treatments have been tested in various trials. While they can cause side effects, they are generally considered safe when managed properly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for colorectal cancer because they offer new ways to tackle the disease. Regorafenib is unique because it targets multiple pathways that help cancer cells grow, making it different from standard treatments that usually focus on just one pathway. On the other hand, combining cetuximab or panitumumab with irinotecan brings a fresh approach by using targeted therapy along with chemotherapy, potentially enhancing the effectiveness against tumors. These innovative strategies could provide more options and hope for patients who don't respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

This trial will compare two treatment approaches for advanced colorectal cancer. Studies have shown that regorafenib, which participants in Arm A may receive, can extend patient survival by blocking proteins that promote cancer cell growth. In Arm B, participants may receive a combination of cetuximab or panitumumab with irinotecan. Research has shown that this combination effectively treats colorectal cancer, particularly in patients with specific genetic traits. Cetuximab and panitumumab are antibodies that inhibit cancer cell growth and spread. These treatments have proven successful in patients with colorectal cancer, especially those with certain genetic profiles. Together, these approaches offer promising options for managing advanced colorectal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Daniel H Ahn

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer that can't be removed by surgery, has spread, and hasn't responded to certain treatments. Participants must have a life expectancy of at least 3 months, adequate organ function, no severe concurrent diseases or recent significant cardiovascular events. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =< 2.5 x ULN (=< 5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior to randomization)

Absolute neutrophil count (ANC) >= 1200/mm^3 (obtained =< 7 days prior to randomization)

I can swallow and keep down pills.

Exclusion Criteria

I have not had major surgery or a significant injury in the last 28 days.

I have or had a pheochromocytoma.

My heart condition does not severely limit my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive regorafenib or anti-EGFR monoclonal antibody therapy, with cycles repeating every 28 days until disease progression or unacceptable toxicity

Variable, up to 20 months

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

3 years

Follow-up at 30 days, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Irinotecan
• Panitumumab
• Regorafenib

Trial Overview The study tests regorafenib in combination with anti-EGFR therapy (cetuximab or panitumumab) versus the reverse order for metastatic colorectal cancer treatment. It aims to see which sequence works better for controlling cancer growth.

How Is the Trial Designed?

Group I: Arm B (cetuximab, panitumumab, irinotecan) Experimental Treatment 3 Interventions

Patients receive cetuximab or panitumumab IV over 30-90 minutes on days 1 and 15. Patients may also receive irinotecan IV on days 1 and 15 as determined by the study doctor. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If received as initial treatment, patients who experience disease progression may switch over to the other treatment regimen, per treating physician discretion.

Group II: Arm A (regorafenib) Experimental Treatment 1 Intervention

Patients receive regorafenib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. If received as initial treatment, patients who experience disease progression may switch over to the other treatment regimen, per treating physician discretion.

Cetuximab is already approved in United States, European Union for the following indications:

Approved in United States as Erbitux for:

• Locally or regionally advanced squamous cell carcinoma of the head and neck
• Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
• BRAF V600E mutation-positive metastatic colorectal cancer

Approved in European Union as Erbitux for:

• Squamous cell carcinoma of the head and neck
• K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10656984/

Triplet‐drug chemotherapy combined with anti‐EGFR ... Our findings show that triplet-drug chemotherapy (FOLFOXIRI) combined with anti-EGFR antibody (panitumumab or cetuximab) represents a very effective ...

2. nature.com nature.com/articles/s41416-021-01477-9

Molecular subtype-specific efficacy of anti-EGFR therapy in ... For CMS2/3 patients there was indeed a better outcome when cetuximab was added to FOLFOX, though this was not significant (PFS HR 0.45, 95% CI ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5764984/

Chemotherapy plus Panitumumab Versus ... Panitumumab and bevacizumab have been widely used in combination with chemotherapy for patients with wild type RAS metastatic colorectal cancer (mCRC).

4. sciencedirect.com sciencedirect.com/science/article/pii/S246829422500005X

Panitumumab versus cetuximab in combination with ... Previous data showed clinically significant activity of cetuximab in combination with irinotecan in patients with irinotecan-refractory colorectal cancer, with ...

5. vectibixhcp.com vectibixhcp.com/efficacy

WT RAS mCRC Study Results & Efficacy Explore study data establishing the efficacy of Vectibix® for newly diagnosed and chemorefractory patients with WT RAS mCRC. See Prescribing and Safety Info ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/125084s273lbl.pdf

ERBITUX (cetuximab) - accessdata.fda.gov The data described below reflect exposure to ERBITUX in 242 patients with K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer (mCRC) [see Warnings ...

7. erbitux.lilly.com erbitux.lilly.com/hcp/mcrc

Metastatic Colorectal Cancer | mCRC | HCP - Erbitux - Eli Lilly ERBITUX provides approximately 22% higher exposure compared to the cetuximab product used in CRYSTAL; however, the safety data from CRYSTAL is consistent in ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30218345/

An Update of Efficacy and Safety of Cetuximab in ... Cetuximab efficacy emerged from studies that were conducted to approve the drug. Cetuximab is well tolerated; its toxicities are caused by its mechanism of ...

9. news.bms.com news.bms.com/news/details/2012/FDA-Approves-ERBITUXR-cetuximab-as-First-Line-Treatment-in-KRAS-Mutation-Negative-Wild-Type-Epidermal-Growth-Factor-Receptor-EGFR-Expressing-Metastatic-Colorectal-Cancer-in-Combination-with-FOLFIRI-Irinotecan-5-Fluorouracil-Leucovorin/default.aspx

FDA Approves ERBITUX(R) (cetuximab) as First-Line ... Serious infusion reactions occurred with the administration of ERBITUX in approximately 3 percent of patients in clinical trials, with fatal ...

10. aetna.com aetna.com/cpb/medical/data/600_699/0684.html

Cetuximab (Erbitux) - Medical Clinical Policy Bulletins Safety data from the 111 patients treated only with cetuximab ... Cetuximab (Erbitux) for metastatic colorectal cancer: Horizon scanning technology briefing.