Sunitinib vs Cediranib for Sarcoma

Recruiting at 2 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, Strong CYP3A4 inhibitors

Disqualifiers: Hypertension, Heart failure, HIV, 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

Compensation: Varies

Number of Visits: 4

34 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: * Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor accounting for less than 1% of soft tissue sarcomas. There is no effective systemic treatment for patients with metastatic ASPS. Little is known with regards to relevant molecular markers as potential therapeutic targets. * Cediranib (AZD2171) and sunitinib (SU011248), oral small molecule inhibitors of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, are showing preliminary evidence of activity in patients with ASPS. Objectives: * Part I: Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. * Part II: Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm. * Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS. Eligibility: * Patients aged greater than or equal to 16 years with histologically or cytologically confirmed metastatic ASPS. * Patients must show evidence of objective disease progression per Response evaluation criteria in solid tumors (RECIST)v1 on scans within the 3-month period immediately preceding enrollment. Both scans used to determine disease progression should have been obtained within this 6-month period. * Patients with newly diagnosed, unresectable, measurable, metastatic ASPS who show clinical evidence of disease progression will be eligible. * Patients must not have received treatment with any VEGF receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed. Design: * Part I: Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles. * Part II: At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period. * Appropriate anatomic imaging studies will be performed at baseline and every 2 cycles for restaging. * The study will be conducted using an optimal two-stage design to rule out an unacceptably low 15% clinical response rate (PR+CR) in favor of a modestly high response rate of 40%. The study will initially enroll 10 evaluable patients in each arm. If 0 or 1 of the 10 patients has a clinical response, then no further patients will be accrued. If 2 or more the first 10 patients have a response, then accrual continues to a total of 22 patients in each arm.

Will I have to stop taking my current medications?

The trial requires that you avoid strong CYP3A4 inhibitors and inducers within 7 to 12 days before and during the study. If you are taking such medications, you should try to switch to other medications 1 week before starting the trial. If you cannot switch, your case will need to be reviewed by the study's principal investigator.

What data supports the effectiveness of the drug Cediranib in treating sarcoma?

Cediranib has shown effectiveness in treating several adult cancers by blocking VEGF receptors, which are involved in the growth of blood vessels that supply tumors. This suggests it might also help in treating sarcoma by cutting off the tumor's blood supply. ^{1 2 3 4 5}

Is cediranib generally safe for humans?

Cediranib has been tested in various studies and is generally well tolerated at doses of 45 mg per day or less, with side effects similar to other drugs that target blood vessel growth. It has been studied in different cancers, showing a safety profile that supports its use in humans. ^{1 3 4 5 6}

How does the drug Sunitinib vs Cediranib for Sarcoma differ from other treatments?

Cediranib and Sunitinib are unique because they both target multiple pathways involved in tumor growth, specifically inhibiting vascular endothelial growth factor (VEGF) receptors, which are crucial for tumor blood supply. This dual approach may offer a novel way to treat sarcoma by cutting off the tumor's blood supply and inhibiting its growth, unlike standard treatments that may not target these specific pathways. ^{1 2 3 6 7}

Research Team

Alice P Chen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for people aged 16 or older with a specific type of cancer called metastatic Alveolar Soft Part Sarcoma (ASPS). They should have measurable disease progression and normal organ/marrow function. Those who've had certain treatments like VEGF receptor tyrosine kinase inhibitors can't join, but prior bevacizumab treatment is okay.

Inclusion Criteria

I am a woman who can have children and I have a negative pregnancy test.

I agree to use two reliable birth control methods if I can have children.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

My thyroid condition cannot be controlled with medication.

I haven't had serious wounds, ulcers, or abdominal issues in the last 28 days.

I have not had a stroke or mini-stroke in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Participants are randomized to receive either cediranib or sunitinib malate orally, once a day in 28-day cycles

16 months

Baseline and every 2 cycles for restaging

Treatment Part II

At disease progression, participants cross over to the other treatment arm after a 2-week wash-out period

16 months

Baseline and every 2 cycles for restaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Treatment Details

Interventions

• Cediranib
• Sunitinib

Trial Overview The trial tests two oral drugs, Cediranib and Sunitinib, which inhibit blood vessel growth in tumors. Participants will randomly receive one drug first and then switch to the other if their cancer progresses. The main goals are to see how well these drugs shrink the tumors and how long patients stay free from disease worsening.

Participant Groups

Group I: Part II - Cross Over Experimental Treatment 14 Interventions

At the time of disease progression, patients will cross over to the other treatment arm after a 2-week wash-out period.

Group II: Part I - Cediranib (30 mg) or Sunitinib Malate (37.5 mg) Orally Experimental Treatment 14 Interventions

Patients will be randomized to receive cediranib (30 mg) or sunitinib malate (37.5 mg) orally, once a day in 28-day cycles.

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

Approved in United States as Cediranib for:

• Alveolar soft part sarcoma

Approved in European Union as Cediranib for:

• Alveolar soft part sarcoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Sunitinib malate is a multi-kinase inhibitor approved for treating advanced renal cell carcinoma and other specific tumors, showing modest antitumor activity in ovarian cancer based on Phase I and II trials.

The drug has an acceptable safety profile, but further research is needed to better understand its toxicity and to explore combination therapies for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. Leone Roberti Maggiore, U., Valenzano Menada, M., Venturini, PL., et al.[2018]

References

1. 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]

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

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

3. 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]

4. 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]

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

The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies. [2013]

7. England pubmed.ncbi.nlm.nih.gov

The potential of sunitinib as a therapy in ovarian cancer. [2018]