Palbociclib + Cetuximab for Colon Cancer

Overseen By Catherine Griffin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: CDK inhibitors, QT prolonging drugs

Disqualifiers: Active infection, CNS metastases, 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: Unknown

Duration: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two drugs, cetuximab (Erbitux) and palbociclib (Ibrance), work together to treat colon cancer that has spread. The goal is to determine if this combination can better manage the disease. It is open to individuals who have tried at least two different chemotherapy treatments for metastatic colon cancer without success. Participants should have a type of colon cancer not linked to specific gene mutations (KRAS, NRAS, or BRAF mutations). As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that you cannot participate if you are on certain prohibited medications that cannot be discontinued or replaced. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that cetuximab, a drug tested in this trial, can help people with advanced colon cancer live longer and respond better to treatment. Most patients with this type of cancer tolerate the drug well.

Palbociclib, on the other hand, is not FDA-approved for colon cancer and is considered experimental in this trial. However, when combined with cetuximab, some patients have experienced benefits without major safety concerns.

One study found that using both drugs together helped patients live without their cancer worsening for about 5.4 months, compared to 2.1 months with other treatments. This suggests the combination might be more effective than some other options, but further research is needed to fully understand its safety.

In summary, while cetuximab is already used in similar cases, palbociclib remains under study. It is important to consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of palbociclib and cetuximab for colon cancer because it targets cancer cells in a novel way. Unlike standard treatments, which often involve chemotherapy, this combination uses palbociclib to inhibit a protein called CDK4/6, slowing down the growth of cancer cells. Cetuximab, on the other hand, targets the epidermal growth factor receptor (EGFR), blocking signals that encourage cancer cell growth. This dual-action approach has the potential to be more effective in halting tumor progression, offering hope for improved outcomes in patients with colon cancer.

What evidence suggests that this treatment might be an effective treatment for colon cancer?

Research has shown that using cetuximab and palbociclib together might help treat advanced colon cancer. In one study, about 33 out of 100 people responded to this treatment, compared to 6 out of 100 who responded to another treatment. However, this combination did not meet all its goals for patients whose cancer did not respond to other treatments, though some benefits were still observed. This treatment remains experimental and is not yet approved by the FDA for colon cancer. Participants in this trial will receive the combination of cetuximab and palbociclib as part of the study's single treatment arm. ^{2 6 7 8 9}

Who Is on the Research Team?

Hanna K. Sanoff

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

Adults with metastatic colorectal cancer who've had at least two prior chemotherapy regimens can join this trial. They must not be pregnant, able to swallow pills, and have no major surgeries in the last 4 weeks. Participants need normal organ function tests and cannot have active infections or CNS metastases. Prior CDK inhibitor treatment is a disqualifier.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I haven't had any major surgeries in the last 4 weeks and all my surgical wounds have healed.

I am not pregnant and can prove it with a test taken in the last 72 hours.

Exclusion Criteria

I am currently being treated for an infection.

I have been treated with a drug targeting CDK before.

I am not taking any medications that can cause long QT syndrome, except for low-dose Ondansetron.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of cetuximab and palbociclib to treat metastatic colorectal cancer

4 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 20 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• Palbociclib

Trial Overview The study is testing the combination of Palbociclib (a drug that inhibits certain proteins) and Cetuximab (an antibody that targets cancer cells) in patients with advanced colon cancer to see if it's effective.

How Is the Trial Designed?

Group I: Open-label, single arm, Phase II Experimental Treatment 2 Interventions

Cetuximab and palbociclib

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

In a study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

Cetuximab, when combined with irinotecan, can provide patients with metastatic colorectal cancer an additional 1.7 to 2.0 years of life, indicating its efficacy as a treatment option.

However, the cost-effectiveness analysis revealed that the treatment is quite expensive, with costs per life year gained ranging from 205,536 to 323,040 Euros, highlighting the financial considerations of using cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. Norum, J.[2019]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12526856/

Phase II single-arm study of palbociclib and cetuximab in ... Regarding response, ORR of the study combination was 33.3%, an improvement from 6.1% with trifluridine-tipiracil and bevacizumab and 19.8% with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03446157

Palbociclib and Cetuximab in Metastatic Colorectal Cancer The combination of Cetuximab (Erbitux®) with palbociclib is not approved by the FDA for treating colon cancer and is considered investigational in this research ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40990835/

Phase II single-arm study of palbociclib and cetuximab in ... Conclusion: While clinical benefit was observed with the combination, it did not meet its pre-specified endpoint for efficacy in patients with ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.088

Phase II single-arm study of palbociclib and cetuximab ... We hypothesized that the addition of the CDK4/6 inhibitor palbociclib to cetuximab would be effective for anti-EGFR rechallenge in KRAS-WT mCRC.

5. academic.oup.com academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyaf305/64372336/oyaf305.pdf

Phase II single-arm study of palbociclib and cetuximab in anti ... The combination of palbociclib and cetuximab did not meet its endpoint of improving 4-month disease control rate in patients with refractory ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03446157

Palbociclib and Cetuximab in Metastatic Colorectal Cancer Palbociclib is not FDA-approved for the treatment of colon cancer, and is considered an investigational drug in this research study. Palbociclib targets a ...

7. withpower.com withpower.com/trial/phase-3-neoplasms-2-2018-676c7

Palbociclib + Cetuximab for Colon Cancer Cetuximab, one of the drugs in the combination, has been shown to improve survival and response rates in patients with metastatic colorectal cancer, especially ...

8. oncologynewscentral.com oncologynewscentral.com/colorectal-cancer/practice-change-in-advanced-colorectal-cancer-combination-outperforms-chemo-for-survival

Practice Change in Advanced Colorectal Cancer Patients who received the drug combination had a median progression-free survival (PFS) of 5.4 months compared with 2.1 months in the ...

9. facebook.com facebook.com/MDAnderson/posts/clinical-trial-results-show-a-combination-of-three-cancer-drugs-could-double-sur/1120974156743497/

Clinical trial results show a combination of three cancer ... Tumor reduction of more than 80% was observed in 42% of the initial patients treated, and responses were durable. 6. NCCN Advocates for ...