Rifampicin + Cediranib for Solid Tumors

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

64 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase I, open study to assess the effect of rifampicin, a marketed drug, on how the body handles the experimental drug cediranib in patients with advanced cancer.

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.

What data supports the effectiveness of the drug Cediranib, AZD2171, for solid tumors?

Cediranib has shown effectiveness in improving progression-free survival in patients with relapsed platinum-sensitive ovarian cancer when combined with chemotherapy. It has also been studied for its efficacy in advanced hepatocellular carcinoma and metastatic castration-resistant prostate cancer, indicating its potential in treating various cancers. ^{1 2 3 4 5}

Is the combination of Rifampicin and Cediranib safe for humans?

Cediranib has been studied in combination with other drugs for cancer treatment, and safety data from these studies suggest it is generally safe for humans, though it may interact with other medications like rifampicin. Always consult with a healthcare provider for personalized advice. ^{1 2 6 7 8}

What makes the drug Rifampicin + Cediranib unique for treating solid tumors?

The combination of Rifampicin and Cediranib is unique because Cediranib can reverse multidrug resistance in tumors by inhibiting certain transport proteins, potentially making cancer cells more sensitive to treatment. Additionally, Cediranib is an oral drug that targets multiple pathways involved in tumor growth, which may offer a novel approach compared to standard treatments. ^{1 2 4 7 9}

Research Team

Michael Sawyer, MD

Principal Investigator

Cross Cancer Institute, Edmonton, AB, Canada

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase I evaluation of the effects of ketoconazole and rifampicin on cediranib pharmacokinetics in patients with solid tumours. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exposure simulation analysis for cediranib (AZD2171) in pooled Phase I/II studies in patients with cancer. [2021]

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

Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer. [2023]

5. England 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. [2021]

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

A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Phase I evaluation of cediranib, a selective VEGFR signalling inhibitor, in combination with gefitinib in patients with advanced tumours. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. [2015]