Vandetanib + Everolimus for Advanced Cancer

VS
Overseen ByVivek Subbiah, MD
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 assess the side effects of combining vandetanib and everolimus for treating advanced cancer that has spread. These drugs may inhibit cancer growth by blocking specific enzymes essential for cancer cell proliferation. The trial seeks participants whose cancer has not responded to standard treatments or who lack other treatment options that could extend survival by at least three months. 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be at least 3 weeks past your last chemotherapy and radiation treatments, and 5 half-lives or 3 weeks past any targeted or biologic therapy.

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

Research shows that using vandetanib and everolimus together is generally safe for treating advanced cancers. In past studies, adults and children with advanced cancers tolerated this combination well. The most common doses tested were 300 mg of vandetanib and 10 mg of everolimus.

Most side effects were manageable, though some negative effects occurred, such as tiredness or digestive issues. Serious problems were rare. Researchers are also testing this combination for other types of cancer, indicating confidence in its safety.

In summary, while this specific trial remains in an early stage, existing research supports the safety of these drugs when used together.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about vandetanib and everolimus for advanced cancer because these drugs target specific pathways involved in cancer growth. Vandetanib works by blocking signals that promote tumor cell division and blood vessel formation, while everolimus inhibits a protein that controls cell growth. This combination approach is different from current treatments that often focus on a single mechanism, potentially offering a more effective strategy to halt cancer progression. By attacking the cancer from multiple angles, these drugs might provide new hope for patients with limited options.

What evidence suggests that vandetanib and everolimus might be effective for advanced cancer?

Research has shown that using vandetanib and everolimus together may help treat advanced cancers. In this trial, participants will receive a combination of these two drugs. One study found that this combination helped patients live longer and reduced tumor size in some cases. In children with advanced cancers, this treatment proved effective and generally well-tolerated. Another study found that using both drugs together worked better than using either one alone for some patients with solid tumors. These findings suggest that vandetanib and everolimus together might benefit people with metastatic cancer.36789

Who Is on the Research Team?

Sarina A. Piha-Paul | MD Anderson ...

Sarina Piha-Paul, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced or metastatic cancer that's resistant to standard therapy, relapsed, or without a survival-improving standard option. They must be weeks past prior treatments, have adequate organ/marrow function and agree to use contraception. Exclusions include certain heart conditions, uncontrolled illnesses, pregnancy/lactation, and hypersensitivity to the drugs tested.

Inclusion Criteria

It has been over 3 weeks since my last chemotherapy.
I agree to use effective birth control or practice abstinence.
My cancer does not respond to standard treatments, has come back, or there are no treatments that could extend my life by at least three months.
See 3 more

Exclusion Criteria

I have a slow heartbeat or heart failure that affects my daily life.
History of hypersensitivity to vandetanib, lactose, murine products, or any component of the formulation
Pregnant or lactating women
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive vandetanib and everolimus orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

14-28 days

What Are the Treatments Tested in This Trial?

Interventions

  • Everolimus
  • Vandetanib
Trial Overview The study tests combining vandetanib and everolimus in patients with widespread cancer. It aims to find the safest dose while observing how these drugs might halt cancer cell growth by inhibiting key enzymes necessary for their proliferation.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (vandetanib, everolimus)Experimental Treatment4 Interventions

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

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Approved in United States as Afinitor for:
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Approved in European Union as Votubia for:
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Approved in United States as Zortress for:

Find a Clinic Near You

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

The combination of vandetanib (VAN) and everolimus (EV) was found to be safe and showed promising antitumor activity in a phase I trial involving 80 patients with advanced solid tumors, with a maximum tolerated dose of 300 mg for VAN and 10 mg for EV.
Out of the evaluable patients, 10% achieved a partial response and 51% had stable disease, with a median overall survival of 10.5 months, indicating that this combination therapy could be effective for patients with refractory solid tumors.
Safety and activity of vandetanib in combination with everolimus in patients with advanced solid tumors: a phase I study.Cascone, T., Sacks, RL., Subbiah, IM., et al.[2022]
The combination of everolimus and vatalanib (PTK/ZK) showed at least additive and potentially synergistic anti-tumor effects in a mouse model of melanoma, enhancing efficacy without increasing toxicity compared to either drug alone.
Pharmacokinetic studies revealed that vatalanib increased the plasma concentration of everolimus, but this interaction did not fully explain the enhanced anti-tumor activity, suggesting that the two drugs may work together through distinct mechanisms.
Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model.O'Reilly, T., Lane, HA., Wood, JM., et al.[2021]
Patients with advanced renal cell carcinoma treated with the combination of lenvatinib (LEN) and everolimus (EVE) experienced a significant improvement in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST), gaining an average of 3.7 months compared to those receiving EVE alone.
The LEN+EVE combination resulted in a 24% relative gain in Q-TWiST, indicating a clinically important benefit in quality survival time for patients who had previously undergone antiangiogenic therapy.
Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) for Lenvatinib plus Everolimus Versus Everolimus Monotherapy in Patients with Advanced Renal Cell Carcinoma.Lee, CH., Wan, Y., Smith, A., et al.[2022]

Citations

Repurposing Vandetanib plus Everolimus for the ...This combination was well tolerated in vivo and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG ...
Everolimus in combination with vandetanib in children, ...Combination of vandetanib and everolimus is active in pediatric patients with advanced cancers. •. Combination of vandetanib and everolimus ...
Vandetanib and Everolimus in Treating Patients WithThis clinical trial is testing two medications, vandetanib and everolimus, to see how well they work together in treating patients with advanced cancer that has ...
Safety and activity of vandetanib in combination with ...VAN + EV is safe, active and provides clinical benefit in some patients with refractory solid cancers.Dual therapy is superior to monotherapy at inhibiting ...
Everolimus in combination with vandetanib in children, ...Conclusions The combination of vandetanib and everolimus showed early activity and tolerable toxicity profile in pediatric patients with ...
6.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/33721621/
Safety and activity of vandetanib in combination ... - PubMedThe MTDs and RP2Ds of VAN + EV are 300 mg and 10 mg, respectively. VAN + EV combination is safe and active in refractory solid tumors.
Safety and activity of vandetanib in combination with ...In fact, an analogous combination of a VEGFR-2/RET plus mTOR inhibitors lenvatinib and everolimus is FDA-approved for metastatic renal cell carcinoma. The ...
Repurposing Vandetanib plus Everolimus for the Treatment of ...Combined vandetanib and everolimus was identified by artificial intelligence as a potential therapy for ACVR1-mutant DIPG, as they synergize in vitro and.
Everolimus in combination with vandetanib in children ...The combination of vandetanib and everolimus showed early activity and tolerable toxicity profile in pediatric patients with advanced cancers.
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