Rifampicin + Cediranib for Solid Tumors

Not currently recruiting at 4 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Disqualifiers: Unstable brain metastases, GI impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the body processes the experimental cancer drug cediranib when combined with the commonly used drug rifampicin. Researchers aim to determine if rifampicin alters the effects of cediranib in individuals with advanced cancer. Participants will take cediranib alone, then with rifampicin, and finally cediranib alone again. This trial suits individuals with prostate cancer unresponsive to other treatments who remain in relatively good health. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that cediranib, the experimental drug in this trial, has been studied for its safety in treating solid tumors. A review of several studies found that cediranib could be a promising treatment for various types of solid tumors, indicating that it has been tested in multiple studies to gather safety information.

One study found that the safety of cediranib in patients with advanced liver cancer was similar to its safety in other solid tumors. This suggests that the drug is generally well-tolerated, although side effects can occur. These side effects might include high blood pressure and tiredness, but they are often manageable.

Cediranib is still under investigation, so researchers continue to learn about its safety and side effects. It is crucial to consult healthcare providers to understand the potential risks and benefits for specific situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about Cediranib, especially when combined with rifampicin, because it targets cancer in a unique way. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Cediranib specifically blocks the growth of blood vessels that tumors need to grow. This mechanism, known as anti-angiogenesis, helps to starve the tumor by cutting off its supply of nutrients. Combining Cediranib with rifampicin might enhance this effect, potentially leading to more effective treatment outcomes for patients with solid tumors.

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

Research has shown that cediranib, which participants in this trial will receive, has promising results in slowing or stopping tumor growth in patients with advanced solid tumors. It has demonstrated encouraging activity against tumors, helping to control their growth. Studies have also explored its use with other drugs like olaparib, supporting its potential effectiveness. However, some trials found that at certain doses, cediranib caused significant side effects, indicating it wasn't well tolerated by patients. Overall, while positive signs exist, more research is needed to fully understand cediranib's effectiveness in treating solid tumors. ^{3 5 6 7 8}

Who Is on the Research Team?

Michael Sawyer, MD

Principal Investigator

Cross Cancer Institute, Edmonton, AB, Canada

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors, specifically those who have prostate cancer that's not responding to standard treatments or when no standard treatment exists. Participants should be able to perform daily activities (WHO PS 0-2), expect to live at least 8 more weeks, and give written consent. People with unstable brain metastases, abnormal blood tests, significant gastrointestinal issues, or poor bone marrow function cannot join.

Inclusion Criteria

Written informed consent

I can take care of myself and perform light activities.

My prostate cancer does not respond to standard treatments.

Exclusion Criteria

Biochemistry/haematology results outside of required ranges

History of significant GI impairment

I do not have unstable brain or spinal cord cancer spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cediranib alone, followed by cediranib plus rifampicin, and then cediranib alone

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cediranib

Trial Overview The study is examining how rifampicin affects the body's handling of cediranib in patients with advanced cancers. It's a Phase I trial which means it’s early in testing and primarily looking at safety and dosage levels of cediranib when taken alongside rifampicin.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

Cediranib alone, followed by cediranib plus rifampicin, followed by cediranib alone.

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?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Cediranib showed some anti-tumor activity in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously undergone docetaxel treatment, with 43.9% of patients remaining progression-free at 6 months and a median progression-free survival of 3.7 months.

The treatment was generally well tolerated, with common side effects including hypertension and fatigue; however, adding prednisone helped reduce some of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer. Dahut, WL., Madan, RA., Karakunnel, JJ., et al.[2023]

Cediranib, when used in combination with chemotherapy and as maintenance therapy, significantly improved progression-free survival (PFS) in women with platinum-sensitive ovarian cancer, showing a hazard ratio of 0.56, indicating a 44% reduction in the risk of disease progression.

While the overall survival (OS) analysis was underpowered due to a reduced number of participants, there was a 14% relative reduction in the risk of death, suggesting that cediranib may still provide meaningful benefits in extending survival time for patients with recurrent ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial. Ledermann, JA., Embleton-Thirsk, AC., Perren, TJ., et al.[2021]

In a study involving 46 patients, the CYP3A4 inhibitor ketoconazole significantly increased the steady-state pharmacokinetics of cediranib, with a 21% increase in AUC and a 26% increase in Cmax, indicating that ketoconazole enhances the drug's absorption and effectiveness.

Conversely, in a separate study with 64 patients, the CYP3A4 inducer rifampicin decreased the pharmacokinetics of cediranib by 39% in AUC and 23% in Cmax, suggesting that rifampicin reduces the drug's effectiveness, highlighting the need for caution when using cediranib with these agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of the effects of ketoconazole and rifampicin on cediranib pharmacokinetics in patients with solid tumours. Lassen, U., Miller, WH., Hotte, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17634482/

Phase I clinical study of AZD2171, an oral vascular ... Once-daily oral AZD2171 at doses of 45 mg or less was generally well tolerated and was associated with encouraging antitumor activity in patients with a broad ...

2. 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.9065

A phase II study of cediranib in combination with olaparib ... We therefore tested the anti-tumor activity of cediranib and olaparib combination in patients (pts) with advanced solid tumors. Here, we report ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1556086415305918

Phase II Study of Cediranib (AZD 2171), an Inhibitor of the ... Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2023/9245663

A Systematic Review and Meta‐Analysis: Safety ... The systematic review yielded 14 eligible trials, comprising 4,387 patients with solid malignant tumors. The analysis results of RCTs showed ...

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8480C00014

Safety and Tolerability Study of AZD2171 in combination ... The purpose of the study is to determine if the maximum tolerated doses of AZD2171, in combination with AZD0530, in treating patients with advanced solid ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5867133/

Population exposure–safety analysis of cediranib for ... Cediranib in combination with olaparib is currently undergoing Phase III clinical trials in patients with ovarian cancer (NCT02446600 and NCT02502266).

8. aacrjournals.org aacrjournals.org/clincancerres/article/19/6/1557/204946/Efficacy-Safety-Pharmacokinetics-and-Biomarkers-of

Efficacy, Safety, Pharmacokinetics, and Biomarkers of ... The mean steady-state PK parameters of cediranib in patients with advanced HCC were largely comparable to values that have been reported for solid tumor ...