Selumetinib + Cyclosporine for Colorectal Cancer

No longer recruiting at 11 trial locations
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and understand the side effects of combining selumetinib and cyclosporine for treating colorectal cancer and other solid tumors that have spread and resist existing treatments. Selumetinib, a targeted therapy, may stop tumor growth by blocking certain enzymes, while cyclosporine, a biological therapy, can influence the immune system and also inhibit tumor growth. This trial may suit those with advanced colorectal cancer who have not responded to standard treatments and have tumors that can be safely biopsied. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have had chemotherapy or radiotherapy within 4 weeks before the study or if you are on certain investigational agents. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that patients with advanced solid tumors generally tolerate the combination of selumetinib and cyclosporine well. In earlier studies, patients experienced manageable side effects, suggesting that severe reactions are uncommon. Evidence also indicates that this treatment is effective against certain types of cancer, which is encouraging.

This trial is in its early stages, specifically Phase 1, which primarily focuses on assessing safety and determining the optimal dose. While early results are positive regarding treatment tolerance, the complete safety profile is still under development. Participants should understand that more detailed safety information will emerge as more patients join the study.12345

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for colorectal cancer, which often include chemotherapy and targeted therapies like bevacizumab or cetuximab, the combination of selumetinib and cyclosporine offers a novel approach. Selumetinib is a MEK inhibitor, which targets a specific pathway (the MAPK/ERK pathway) that plays a key role in cancer cell growth. Cyclosporine, typically known for its use in preventing organ transplant rejection, has properties that may enhance the efficacy of selumetinib by modulating drug resistance mechanisms. Researchers are excited about this combo because it tackles the cancer from a new angle, potentially overcoming resistance issues and improving treatment outcomes.

What evidence suggests that selumetinib and cyclosporine might be an effective treatment for colorectal cancer?

This trial will evaluate the combination of selumetinib and cyclosporine for treating colorectal cancer. Research has shown that this combination may help treat colorectal cancer and other solid tumors. Selumetinib blocks certain enzymes that tumors need to grow and has proven effective in lab studies, especially for cancers with specific genetic changes like BRAF or KRAS. Cyclosporine affects the immune system, and when combined with selumetinib, it has shown promise in models that mimic human cancer. Early results suggest that using both drugs together might be more effective than using each one alone. While more research is needed, these initial findings offer hope for people with colorectal cancer.13678

Who Is on the Research Team?

CH

Christopher H Lieu

Principal Investigator

University of Texas MD Anderson Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors or colorectal cancer that's spread and can't be treated or controlled. They must have had certain treatments, not have specific mutations, and be healthy enough overall (good organ function, no severe heart conditions). Participants need to consent, use contraception if needed, and have a life expectancy over 3 months.

Inclusion Criteria

Serum albumin >= 2.5 g/dl
My cancer can be measured using specific criteria.
My advanced cancer does not respond to standard treatments or no standard treatment exists.
See 20 more

Exclusion Criteria

Patients with hyponatremia (sodium < 130 mmol/L)
My blood calcium level is below 8.4 mg/dL, but I can take supplements to increase it.
I haven't had a stroke, mini-stroke, or blood clot in my lungs in the last 6 months.
See 22 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive selumetinib and cyclosporine orally in a dose-escalation study. Selumetinib is given twice daily starting on day -7 of course 1, and cyclosporine is given twice daily starting on day -3 of course 1. Both drugs are then administered on days 1-28 of each 28-day cycle.

28 days per cycle
Daily oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including assessment of adverse events and progression-free survival.

Up to 30 days

What Are the Treatments Tested in This Trial?

Interventions

  • Cyclosporine
  • Selumetinib
Trial Overview The trial tests selumetinib combined with cyclosporine to see the effects on tumor growth by blocking enzymes needed for cell growth and modifying immune responses. It aims to find the best dose with acceptable side effects in patients whose cancers haven't responded to standard therapies.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (selumetinib and cyclosporine)Experimental Treatment4 Interventions

Cyclosporine is already approved in European Union, United States, Canada, Japan for the following indications:

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Approved in European Union as Neoral for:
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Approved in United States as Neoral for:
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Approved in Canada as Neoral for:
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Approved in Japan as Neoral for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Citations

Phase II study of selumetinib (AZD6244, ARRY-142886) ...We conclude that AZD6244 is effective in colorectal cancer cell lines with BRAF or KRAS mutations. Sensitivity to MEK1/2 inhibition ...
A phase IB study of the combination of selumetinib ...Methods: Patients with advanced solid tumors were treated with the combination of selumetinib and CsA in dose escalation followed by an ...
Selumetinib and Cyclosporine in Treating Patients With ...Giving selumetinib and cyclosporine may be a better treatment for solid tumors or colorectal cancer. Detailed Description. PRIMARY OBJECTIVES: I. To ...
PMC Search UpdateThe combination of selumetinib and cyclosporin A (CsA), a non-canonical Wnt pathway modulator, demonstrated antitumor activity in mCRC patient-derived ...
A phase IB study of the combination of selumetinib (AZD6244Conclusions: Selumetinib in combination with cyclosporin A appears to be well-tolerated with evidence of activity in solid tumors. Expansion cohort will ...
A phase IB study of the combination of selumetinib (AZD6244A phase IB study of the combination of selumetinib (AZD6244; ARRY-142886) and cyclosporin A (CsA) in patients with advanced solid tumors with an expansion ...
Record History | ver. 61: 2015-02-26 | NCT02188264This phase I trial studies the side effects and best dose of selumetinib when given together with cyclosporine in treating patients with solid tumors or ...
8.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/25322874/
Phase II study of selumetinib (AZD6244, ARRY-142886) ...We examined the efficacy and safety of selumetinib with irinotecan in second-line therapy. Methods: Patients with K-RAS mutated colorectal cancer, progressing ...
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