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

59 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Panitumumab for colorectal cancer?

Panitumumab has been shown to help patients with a specific type of colorectal cancer (wild-type KRAS tumors) live longer without their cancer getting worse when used alone or with chemotherapy, compared to those who only received supportive care. ^{1 2 3 4 5}

Is the combination of Panitumumab and Trametinib safe for treating colorectal cancer?

Panitumumab has been studied for colorectal cancer and can cause serious side effects like skin rash, diarrhea, and dehydration. It was found to increase the risk of severe side effects and death when combined with certain other treatments. Trametinib, not mentioned in the provided studies, is known to have its own side effects, so combining it with Panitumumab should be done cautiously. ^{1 2 3 6 7}

How is the drug Panitumumab + Trametinib unique for treating colorectal cancer?

Panitumumab is a unique drug for treating metastatic colorectal cancer because it specifically targets the epidermal growth factor receptor (EGFR) and is used for patients with wild-type KRAS tumors, especially after other chemotherapy regimens have failed. It is often combined with other treatments to improve progression-free survival in these patients. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II clinical trial studies how well panitumumab with or without trametinib works in treating patients with stage IV colorectal cancer. Immunotherapy with monoclonal antibodies, such as panitumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving panitumumab with or without trametinib may work better in treating patients with stage IV colorectal cancer.

Research Team

Christine Parseghian

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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, 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]

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]

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]

References

1. United States 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. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

[Panitumumab]. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Panitumumab (vectibix). [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. [2018]

6. England pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]