Cediranib for Sarcoma

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticonvulsants, Antiretrovirals, others

Disqualifiers: Uncontrolled hypertension, Diabetes, Heart failure, 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: 2

Duration: 16.9 cycles for adults, 34.7 cycles for pediatric patients

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the experimental drug Cediranib can slow or stop tumor growth in individuals with alveolar soft part sarcoma, a rare cancer in the body's connective tissues. Cediranib blocks the formation of new blood vessels, which tumors need to grow. Individuals diagnosed with alveolar soft part sarcoma and inoperable tumors might be suitable for this trial. Participants will take the medication daily and undergo regular health checks to monitor the drug's effects and any side effects. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

The trial protocol does not clearly specify if you must stop taking your current medications. However, if you are taking medications that affect the activity of the trial drug, the principal investigator will review your case. If you have brain metastases and are on certain anticonvulsants, you may need to switch medications one week before starting the trial.

Is there any evidence suggesting that cediranib is likely to be safe for humans?

Research shows that cediranib, the treatment under study, has been tested in patients with a rare cancer called alveolar soft part sarcoma. In these studies, most patients tolerated cediranib well, and reports indicate promising safety results with long-term use.

Some patients experienced side effects, with high blood pressure and tiredness being common. However, these side effects were manageable. Cediranib remains experimental and is not yet approved by the FDA for any condition, indicating that more information is needed about its safety and effectiveness. Nonetheless, the safety data collected so far is encouraging for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Cediranib is unique because it targets the blood vessels that supply nutrients to the tumor, effectively starving it, which is known as anti-angiogenesis. This approach is different from traditional treatments like chemotherapy, which targets rapidly dividing cells indiscriminately. Researchers are excited about Cediranib because it offers a more targeted mechanism of action, potentially leading to fewer side effects and improved outcomes for patients with sarcoma.

What evidence suggests that cediranib might be an effective treatment for sarcoma?

Research has shown that cediranib, which participants in this trial will receive, may help treat alveolar soft part sarcoma (ASPS). In studies, cediranib shrank tumors in 35% of patients. This drug stops the growth of new blood vessels, which tumors need to grow and spread. Patients in earlier trials reported feeling better, suggesting that cediranib could be a promising option for those with ASPS. These findings support the potential of cediranib as an effective treatment for this challenging cancer. ^{3 6 7 8 9}

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?

Adults diagnosed with alveolar soft part sarcoma can join this trial. They must have a tumor that's measurable on scans, be in relatively good health, and not pregnant or breastfeeding. Participants need to have normal organ function and blood pressure, and cannot be taking certain drugs that affect kidney function or interact with the study drug.

Inclusion Criteria

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 millimeters with conventional techniques or as greater than or equal to 10 millimeters with spiral computed tomography (CT) scan.

Body surface area (BSA) greater than or equal to 1.04 square meter.

Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 for adults, Karnofsky performance status greater than or equal to 50% for pediatric patients greater than 10 years of age, and Lansky performance status greater than or equal to 50 for pediatric patients less than or equal to 10 years of age.

Exclusion Criteria

Mean QTc greater than 500 msec (with Bazett's correction) in screening electrocardiogram or history of familial long Q wave, T wave (QT) syndrome.

Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart.

Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD2171 by mouth once a day in 28-day cycles. Adult patients receive 30 mg daily, while pediatric patients receive 12 mg/m² daily.

16.9 cycles for adults, 34.7 cycles for pediatric patients

Clinic visit every 2 weeks during cycles 1 and 2, then at the start of each subsequent cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CT scans for restaging and blood pressure monitoring.

4 weeks

Optional Biopsy

Optional biopsies performed in adult patients at baseline, after 3-5 days of treatment, and after completion of 4 weeks of therapy to evaluate drug effect.

What Are the Treatments Tested in This Trial?

Interventions

• Cediranib (AZD2171)

Trial Overview The trial is testing AZD2171 (cediranib), an experimental drug designed to stop tumors from growing new blood vessels. Patients will take cediranib daily in 28-day cycles, recording doses and side effects in a diary. Their response to treatment will be monitored through regular clinic visits, tests, scans, and possibly biopsies.

How Is the Trial Designed?

Group I: Cediranib (AZD2171) Treatment Experimental Treatment 1 Intervention

Adult participants will be treated with 30 mg by mouth once a day for 28 days (28-day cycles). Pediatric participants (\<16 years old) will be treated with 12 mg/m\^2/day once a day for 28 days (28-day cycles).

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

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. 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 ...

4. 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 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00942877?cond=%22Sarcoma,%20Alveolar%20Soft%20Part%22&viewType=Table&rank=2&tab=results

Phase II Study of Cediranib (AZD2171) in Patients With ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31160249/

a double-blind, placebo-controlled, randomised, phase 2 trial Cediranib, a tyrosine-kinase inhibitor, has shown substantial activity in ASPS in non-randomised studies.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4561207/

A Phase I trial and PK Study of Cediranib (AZD2171) ... Preclinical tests of cediranib in pediatric cancer showed improved activity when combined with multiple agents in some, but not all, models(7–9). Phase I adult ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00942877

NCT00942877 | Phase II Study of Cediranib (AZD2171) in ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...