Sunitinib vs Cediranib for Sarcoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two potential treatments, cediranib (AZD2171) and sunitinib, for a rare cancer called alveolar soft part sarcoma (ASPS). Researchers aim to evaluate the effectiveness of these treatments individually and whether they remain effective if switched when the cancer progresses. Individuals with ASPS that has spread, cannot be surgically removed, and have recently experienced worsening symptoms might be suitable for the trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in ASPS treatment.

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.

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

Previous studies have shown that both cediranib and sunitinib are safe for patients. Research indicates that cediranib is generally well-tolerated, with an acceptable safety profile, particularly for patients with alveolar soft part sarcoma. Regular reviews by safety committees have confirmed this.

Sunitinib also has a known safety profile, as demonstrated in studies with patients who have various types of cancer. Some common side effects have been observed, but they align with existing knowledge about the drug. Sunitinib's use in other conditions has provided researchers with a good understanding of its effects.

Both treatments have undergone prior study, and while all medications can have side effects, these drugs have demonstrated safe use in patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Cediranib and Sunitinib offer unique approaches to targeting sarcoma. Unlike standard chemotherapy, which attacks all rapidly dividing cells, Cediranib and Sunitinib specifically target blood vessels that supply the tumor, aiming to cut off its nutrient supply. Cediranib is known for its action as a VEGFR inhibitor, blocking signals that promote blood vessel growth, while Sunitinib has a broader spectrum, targeting multiple receptor tyrosine kinases involved in tumor growth and progression. This targeted approach not only promises increased effectiveness but may also reduce some of the harsh side effects associated with traditional chemotherapy.

What evidence suggests that this trial's treatments could be effective for sarcoma?

This trial will compare Cediranib and Sunitinib for treating sarcoma. Research has shown that Cediranib, which participants in this trial may receive, holds promise for treating alveolar soft part sarcoma (ASPS). In studies, about 35% of patients experienced a noticeable decrease in tumor size, indicating that Cediranib can effectively target ASPS tumors.

Sunitinib, another treatment option in this trial, has proven effective in treating other cancers, such as gastrointestinal stromal tumors and kidney cancer. Although not specifically approved for ASPS, similar trials have shown it can stabilize the disease in most cases. This suggests Sunitinib might help manage ASPS by controlling tumor growth rather than shrinking them. ^{4 5 6 7 8}

Who Is on the Research Team?

Alice P Chen, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.

Greater than 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart or 24-hour urine protein of > 1 g

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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/NCT00942877

NCT00942877 | Phase II Study of Cediranib (AZD2171) in ... The drug has had initial clinical trials, and researchers are interested in determining whether cediranib is effective in inhibiting tumor growth in individuals ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3677840/

Cediranib for Metastatic Alveolar Soft Part Sarcoma - PMC Cediranib produced antitumor activity as a single agent in seven patients with metastatic ASPS during phase I and II trials; four patients had a confirmed ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23630200/

Cediranib for metastatic alveolar soft part sarcoma - PubMed Results: Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2009.27.15_suppl.10523

Activity of cediranib, a highly potent and selective VEGF ... Four patients had a best response of partial response, two patients had a confirmed reduction in maximum tumor diameter of ≥10% and <30% and one patient ...

5. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30215-3/fulltext

Cediranib in patients with alveolar soft-part sarcoma ... Cediranib, a tyrosine-kinase inhibitor, has shown substantial activity in ASPS in non-randomised studies. The Cediranib in Alveolar Soft Part ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6803032/

Cediranib Phase II Study in Children with Metastatic ... Cediranib has an acceptable safety profile. Keywords: cediranib, alveolar soft part sarcoma, pediatric, phase II study. INTRODUCTION. Alveolar soft part sarcoma ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31502400/

Cediranib phase-II study in children with metastatic alveolar ... Cediranib has an acceptable safety profile. Trial registration: ClinicalTrials.gov NCT00942877. Keywords: alveolar soft-part sarcoma; cediranib; pediatric; ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00942877

NCT00942877 | Phase II Study of Cediranib (AZD2171) in ... The drug blocks the creation of new blood vessels. The drug has had initial clinical trials, and researchers are interested in determining whether cediranib is ...