Cediranib + Selumetinib for Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: QT prolonging agents

Disqualifiers: Uncontrolled illness, Cardiac conditions, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of two experimental drugs, cediranib maleate and selumetinib sulfate, for individuals with inoperable solid tumors. These drugs block specific enzymes and blood flow to inhibit tumor growth. The trial is suitable for those with solid tumors who have exhausted standard treatment options and can travel to the Mayo Clinic for follow-ups. 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 treatment.

Do I need to stop 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 are receiving other investigational treatments or certain therapies close to the trial start date. 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 shows that taking cediranib and selumetinib together can cause some side effects. In earlier studies, some patients experienced heart-related problems with both drugs, indicating that not everyone found the combination easy to handle. These studies aim to find the right dose that patients can manage without too many issues.

Despite the side effects, both drugs have shown promise in treating tumors. Cediranib cuts off the blood supply to tumors, while selumetinib stops enzymes that help tumors grow. Notably, selumetinib is already approved for use in children with a specific type of tumor, indicating its safety in certain cases.

In summary, while the combination can cause some side effects, it also offers potential benefits. Ongoing research focuses on finding the safest way to use these drugs together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cediranib and Selumetinib for cancer because these drugs work together to tackle the disease in a novel way. Cediranib is an angiogenesis inhibitor, which means it cuts off the blood supply that tumors need to grow. On the other hand, Selumetinib targets the MAPK/ERK pathway, which is crucial for cancer cell survival and proliferation. Unlike traditional chemotherapy that attacks rapidly dividing cells indiscriminately, this combination specifically targets the pathways and blood vessels that fuel cancer growth, potentially leading to fewer side effects and more precise treatment.

What evidence suggests that cediranib maleate and selumetinib sulfate might be effective for solid malignancies?

Research has shown that using cediranib maleate and selumetinib sulfate together may effectively stop tumors from growing. In this trial, participants will receive both cediranib, which blocks the blood vessels that feed the tumor, and selumetinib, which targets enzymes that help cancer cells grow. Studies have found that this combination can stop tumors from growing and spreading more effectively than using each drug alone. Trials have generally shown both drugs to be well-tolerated, with patients experiencing fewer serious side effects. These promising early results suggest this treatment could be effective for various solid cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Brian A. Costello

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients with solid tumors, including melanoma, who have no standard curative therapy available. Participants must have a certain level of blood cells and organ function, be able to consent, and not be pregnant or nursing. They should also agree to use contraception and return for follow-up visits.

Inclusion Criteria

My cancer cannot be surgically removed and there's no standard treatment for it.

I agree to give blood samples and my stored tumor tissue for research.

Willing to return to Mayo for follow up

Exclusion Criteria

You cannot participate in this study if you are pregnant, breastfeeding, not using birth control, have certain medical conditions, are currently taking certain medications, have certain laboratory test results, have certain medical history, or have had certain medical procedures recently.

I haven't had certain cancer treatments in the last 28-42 days and have recovered from their effects.

You have uncontrolled high blood pressure, severe heart failure, fast irregular heart rate, recent heart attack or angina, or untreated brain or central nervous system tumors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cediranib maleate and selumetinib sulfate orally. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Dose-escalation

Determine the maximally tolerated dose of the drug combination through dose-escalation study.

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Cediranib Maleate
• Selumetinib Sulfate

Trial Overview The study is testing the combination of two drugs, Cediranib Maleate and Selumetinib Sulfate, to see if they can halt tumor growth by blocking enzymes needed for cell growth or cutting off the tumor's blood supply. The trial aims to find the safest doses with the least side effects.

How Is the Trial Designed?

Group I: Treatment (cediranib maleate, selumetinib) Experimental Treatment 6 Interventions

Patients receive cediranib maleate PO QD and selumetinib sulfate PO QD or BID on days 1-28 (days 8-28 of cycle 1). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cycles may be extended to 12 weeks after 1 year of study treatment.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Cediranib, a potent inhibitor of vascular endothelial growth factor signaling, was found to be generally well tolerated at doses of 30 mg/day or less in Japanese patients with advanced solid tumors, with the maximum tolerated dose identified as 30 mg/day due to dose-limiting toxicities at higher doses.

In terms of efficacy, out of 32 evaluable patients, two experienced partial responses and 24 maintained stable disease for at least 8 weeks, indicating promising antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, dose escalation and pharmacokinetic study of cediranib (RECENTIN), a highly potent and selective VEGFR signaling inhibitor, in Japanese patients with advanced solid tumors. Yamamoto, N., Tamura, T., Yamamoto, N., et al.[2022]

The maximum-tolerated dose (MTD) of cediranib in children with recurrent CNS tumors was initially set at 32 mg/m²/day, but excessive toxicities led to concerns about its long-term tolerability.

At a lower dose of 20 mg/m²/day, cediranib still showed poor tolerability, indicating that both doses may not be suitable for extended treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. Kieran, MW., Chi, S., Goldman, S., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01364051?term=SELUMETINIB%20SULFATE&rank=10

Cediranib Maleate and Selumetinib Sulfate in Treating ... This phase I trial studies the side effects and best dose of cediranib maleate and selumetinib sulfate in treating patients with solid malignancies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8766914/

Phase I study of cediranib, an oral VEGFR inhibitor, in ... Preclinical data with cediranib, an inhibitor of all 3 VEGF receptors, in combination with selumetinib, an inhibitor of MEK 1/2, demonstrated improved tumor ...

3. aacrjournals.org aacrjournals.org/cancerres/article/71/8_Supplement/629/574739/Abstract-629-MEK-inhibition-by-selumetinib-AZD6244

Abstract 629: MEK inhibition by selumetinib (AZD6244 ... Results: In both models, selumetinib or cediranib were well tolerated and inhibited tumor growth and metastasis with efficacy superior to ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804919302837

Novel phase I trial design to evaluate the addition of ... Novel trial design to evaluate cediranib and selumetinib independently with chemoradiotherapy in patients with locally advanced rectal cancer.

5. withpower.com withpower.com/trial/phase-1-melanoma-4-2011-df60e

Cediranib + Selumetinib for Cancer · Info for Participants This phase I trial studies the side effects and best dose of cediranib maleate and selumetinib sulfate in treating patients with solid malignancies.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34515877/

Phase I study of cediranib, an oral VEGFR inhibitor ... - PubMed Conclusions: Cediranib and selumetinib in combination on a continuous schedule was not tolerable, with patients experiencing cardiovascular and ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804919302837

Novel phase I trial design to evaluate the addition of ... The main objective of this trial was to establish the maximum tolerated dose (MTD) of both cediranib and selumetinib in combination with standard CRT for rectal ...

8. merck.com merck.com/news/koselugo-selumetinib-showed-significant-and-clinically-meaningful-improvement-in-objective-response-rate-versus-placebo-in-adults-with-neurofibromatosis-type-1-who-have-symptomatic-inoperable/

KOSELUGO® (selumetinib) Showed Significant and ... These results showed reduction in tumor volume, building on the established safety and efficacy profile of KOSELUGO in certain children.