Panitumumab + Trametinib for Colorectal Cancer

Overseen By Christine Parseghian

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: MEK inhibitors

Disqualifiers: Brain metastasis, Lung disease, Cardiac disease, Pregnancy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Variable, based on disease progression

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the drug panitumumab, alone or combined with trametinib, for individuals with stage IV colorectal cancer. Panitumumab, a monoclonal antibody, may assist the immune system in fighting cancer, while trametinib, a targeted therapy, could inhibit cancer cell growth. The trial includes different groups based on specific genetic mutations in the cancer, which can influence treatment response. Individuals with stage IV colorectal cancer who have not responded to other treatments and have certain genetic test results may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications, but it mentions that you cannot use any prohibited medications. It's best to discuss your current medications with the trial team to see if they are allowed.

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

Research has shown that panitumumab, when used alone, is generally well-tolerated by patients. The PARADIGM and PRIME trials found that serious side effects are uncommon, with only about 2.5% of patients experiencing treatment-related deaths. Most patients manage it well, and the FDA has already approved it for other uses in colorectal cancer.

However, combining panitumumab with trametinib tends to be more taxing on the body. Although many patients experienced tumor shrinkage, the combination led to more side effects. Some patients had to discontinue treatment due to these reactions. Prospective trial participants should consider these points and discuss them with their doctor. ^{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 a unique approach by combining panitumumab and trametinib. Unlike standard treatments that primarily focus on chemotherapy, this combination targets specific mutations in cancer cells. Panitumumab is an antibody that targets the EGFR receptor, while trametinib inhibits a protein called MEK, which is part of a signaling pathway often overactive in cancer cells. This targeted strategy could potentially be more effective with fewer side effects, offering new hope for patients whose cancer has specific genetic mutations.

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

Research has shown that panitumumab effectively treats advanced colorectal cancer, particularly in patients with normal RAS genes. Studies have found that adding panitumumab to chemotherapy can significantly extend life, with some patients living for more than three years. Many patients also experienced tumor shrinkage or halted growth. In this trial, participants in Cohorts 1 and 3 will receive panitumumab, with Cohort 1 focusing on patients with EGFR ectodomain mutations and Cohort 3 on those without EGFR ectodomain, KRAS, NRAS, or BRAF mutations.

For trametinib, research indicates it can slow tumor growth, particularly in colorectal cancer with KRAS mutations. This drug blocks certain enzymes that cancer cells need to grow. While trametinib alone has limited effectiveness in some solid tumors, it may enhance treatment when combined with other therapies, like panitumumab. In this trial, participants in Cohort 2 will receive a combination of trametinib and panitumumab, potentially providing a stronger approach to fighting colorectal cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Christine Parseghian

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with stage IV colorectal cancer who have specific gene mutations (KRAS, NRAS, BRAF, MEK) and have progressed after anti-EGFR therapy. They must not have had certain treatments recently and should be generally healthy with good organ function. Women of childbearing age need a negative pregnancy test and agree to use contraception.

Inclusion Criteria

My cancer progressed after treatment with specific chemotherapy drugs or I can't tolerate some of them due to a condition or side effects.

Blood counts performed within 3 weeks prior to starting study therapy must have platelets >= 100,000/mm^3

Blood counts performed within 3 weeks prior to starting study therapy must have hemoglobin >= 9 g/dL

Exclusion Criteria

Known human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection; subjects with laboratory evidence of cleared HBV and HCV infection will be permitted

I am not taking any medications that are not allowed in the study.

I am unable or unwilling to follow the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive panitumumab with or without trametinib based on their cohort assignment. Treatment cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Variable, based on disease progression

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 24 months.

24 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Panitumumab
• Trametinib

Trial Overview The study tests the effectiveness of panitumumab alone or combined with trametinib in treating advanced colorectal cancer. Panitumumab is an immunotherapy drug while trametinib blocks enzymes that help tumor cells grow. The goal is to see if combining these drugs improves patient outcomes.

How Is the Trial Designed?

Group I: Cohort 3 (panitumumab) Experimental Treatment 2 Interventions

Patients without EGFR ectodomain, KRAS, NRAS, or BRAF mutation receive panitumumab as in Cohort 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Cohort 2.

Group II: Cohort 2 (panitumumab, trametinib) Experimental Treatment 3 Interventions

Patients with KRAS, NRAS, or BRAF mutation receive trametinib PO QD on days 1-14 and panitumumab as in Cohort 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group III: Cohort 1 (panitumumab) Experimental Treatment 2 Interventions

Patients with EGFR ectodomain mutation receive panitumumab IV over 30-90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Cohort 2.

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

Approved in European Union as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Approved in United States as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Panitumumab is a human monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which plays a crucial role in the growth and spread of cancer cells, specifically in metastatic colorectal carcinoma.

It is used as a single-agent treatment for patients whose cancer has progressed after standard chemotherapy regimens, including fluoropyrimidine, oxaliplatin, and irinotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab (vectibix). Gemmete, JJ., Mukherji, SK.[2021]

Panitumumab, when combined with chemotherapy, significantly prolongs progression-free survival in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival compared to chemotherapy alone, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: a review of its use in metastatic colorectal cancer. Keating, GM.[2021]

Panitumumab, an anti-EGFR monoclonal antibody, significantly improves progression-free survival when combined with chemotherapy in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival when combined with certain chemotherapy regimens, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. Keating, GM.[2018]

In a phase 2 study involving 148 patients with metastatic colorectal cancer, panitumumab demonstrated a 9% overall response rate and a median progression-free survival of 14 weeks, indicating its efficacy as a treatment option for patients who had previously failed other therapies.

Panitumumab was generally well tolerated, with manageable side effects; 95% of patients experienced skin toxicity, but only 5% had severe reactions, suggesting that while dermatologic issues are common, they are not typically severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Hecht, JR., Patnaik, A., Berlin, J., et al.[2018]

A clinical trial showed that adding panitumumab to bevacizumab and chemotherapy for first-line treatment of metastatic colorectal cancer resulted in worse progression-free survival and increased toxicity compared to bevacizumab and chemotherapy alone.

Patients receiving panitumumab experienced a higher incidence of severe adverse events (87% vs. 72%) and a greater risk of death (9% vs. 4%), leading to the conclusion that panitumumab should not be recommended in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. Giusti, RM., Cohen, MH., Keegan, P., et al.[2018]

Panitumumab (Vectibix) was evaluated in a trial with 463 patients suffering from advanced colorectal cancer, showing a mean progression-free survival (PFS) of 96 days compared to 60 days for those receiving only best supportive care, indicating a significant benefit in delaying disease progression.

Despite the improvement in PFS and an objective response rate of 8%, there was no difference in overall survival between the treatment groups, leading to accelerated approval by the FDA with the requirement for further confirmation of clinical benefit for full approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Giusti, RM., Shastri, K., Pilaro, AM., et al.[2020]

Panitumumab (Vectibix) is approved for treating metastatic colorectal cancer specifically in patients with EGFR-expressing tumors that have non-mutated K-ras genes after standard chemotherapy has failed.

In a phase III study, patients receiving panitumumab along with best supportive care experienced significantly longer progression-free survival compared to those who only received best supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Panitumumab]. Musch, A.[2018]

Citations

1. vectibixhcp.com vectibixhcp.com/efficacy

WT RAS mCRC Study Results & Efficacy In patients with left-sided tumors, Vectibix® significantly increased overall survival with median OS of 37.9 months for Vectibix® plus mFOLFOX6 vs 34.3 months ...

2. vectibix.com vectibix.com/learn-about-vectibix-clinical-trial-results

mCRC Clinical Trial Results | Vectibix® (panitumumab) The PRIME clinical trial showed the benefits of adding Vectibix to chemotherapy for people newly diagnosed with wild-type RAS metastatic colorectal cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4419154/

Panitumumab in Metastatic Colorectal Cancer Efficacy results were generally similar between treatments. Overall, the ORR was 70 % and was 74 % for panitumumab + FOLFOX4 versus 67 % for panitumumab + ...

4. oncotarget.com oncotarget.com/news/pr/new-study-suggests-panitumumab-with-low-dose-capecitabine-as-a-safer-effective-maintenance-treatment-for-advanced-colorectal-cancer/

New Study Suggests Panitumumab with Low-Dose ... The results showed that patients had a median progression-free survival of 18 months and a median overall survival of 45 months, indicating a ...

5. vectibixhcp.com vectibixhcp.com/efficacy/prime-clinical-data

PRIME Study Design & Clinical Data | Vectibix® (panitumumab) Review the design and results of the PRIME study, a phase 3, open-label, randomized multicenter study of newly diagnosed patients with WT RAS mCRC.

6. vectibixhcp.com vectibixhcp.com/efficacy/paradigm-clinical-data

PARADIGM Study Design & Clinical Data Assess design, outcome and safety information from the PARADIGM phase 3 study of newly diagnosed patients with WT RAS mCRC. See Prescribing and Safety Info ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7659902/

Efficacy and safety of panitumumab in a cohort of patients ... Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer.

8. sciencedirect.com sciencedirect.com/science/article/pii/S095980492400131X

A meta-analysis of efficacy and safety data from head-to- ... In PARADIGM after a median follow-up time of 61 months, there were 10 (2.5%) treatment-related deaths in the panitumumab arm compared to 2 (0.5 ...