Cediranib + Selumetinib for Cancer

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

19 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of cediranib maleate and selumetinib sulfate in treating patients with solid malignancies. Cediranib maleate and selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cediranib maleate may also stop the growth of tumor cells by blocking blood flow to the tumor.

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.

What data supports the effectiveness of the drug combination Cediranib and Selumetinib for cancer?

Research shows that combining Cediranib, which blocks blood vessel growth in tumors, with Selumetinib, which stops cancer cell growth signals, can improve tumor control in experimental models. This combination has shown promise in preclinical studies for better managing tumor growth and spread. ^{1 2 3 4 5}

Is the combination of Cediranib and Selumetinib safe for humans?

The combination of Cediranib and Selumetinib has been studied for safety in patients with advanced solid tumors. These studies, including phase I trials, primarily focused on evaluating the tolerability and safety of the drugs, indicating that they have been tested for safety in humans. ^{1 5 6 7 8}

How is the drug combination of Cediranib and Selumetinib unique for cancer treatment?

The combination of Cediranib and Selumetinib is unique because it targets two different pathways involved in cancer growth: Cediranib inhibits all three vascular endothelial growth factor (VEGF) receptors, which are crucial for blood vessel growth in tumors, while Selumetinib inhibits MEK 1/2, a key part of the cell signaling pathway that promotes cancer cell growth. This dual approach may improve tumor control compared to targeting a single pathway. ^{1 2 4 8 9}

Research Team

Brian A. Costello

Principal Investigator

Mayo Clinic

Eligibility Criteria

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.

Your alkaline phosphatase level should be within a certain range based on the blood test taken within the last three weeks.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Phase I study of cediranib, an oral VEGFR inhibitor, in combination with selumetinib, an oral MEK inhibitor, in patients with advanced solid malignancies. [2022]

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

Cediranib plus FOLFOX/CAPOX versus placebo plus FOLFOX/CAPOX in patients with previously untreated metastatic colorectal cancer: a randomized, double-blind, phase III study (HORIZON II). [2015]

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

Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours. [2018]

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

Cediranib in combination with various anticancer regimens: results of a phase I multi-cohort study. [2021]

6. Germany 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. [2022]

7. Germany 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. [2018]

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

Combination testing of cediranib (AZD2171) against childhood cancer models by the pediatric preclinical testing program. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Anti-tumour and anti-vascular effects of cediranib (AZD2171) alone and in combination with other anti-tumour therapies. [2013]