Enhanced MRI for Cervical Cancer

Recruiting at 2 trial locations

Overseen By Oguz Akin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Allergy to gadolinium, Pregnancy, Breastfeeding, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new type of MRI scan designed to capture clearer, more detailed images of tumors in women with gynecologic cancer. The focus is on dynamic contrast-enhanced (DCE) MRI, which operates faster and reduces image blurring, potentially aiding doctors in making better treatment decisions. The study uses a contrast agent called gadobutrol (also known as Gadavist or Gadobutrol Injection), which has FDA approval. Women newly diagnosed with gynecologic cancer and scheduled for pelvic MRI as part of their standard care may be suitable for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking advancements in imaging technology.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it is important to discuss your medications with the study team to ensure they do not interfere with the MRI or contrast agent used in the study.

What prior data suggests that this DCE MRI technique is safe for use in cervical cancer imaging?

Research has shown that Gadobutrol, the contrast dye used in this study's MRI scans, has been safe for most patients over the years. In large studies, only 3.4% of patients experienced side effects related to the dye. Serious side effects were even rarer, occurring in less than 0.1% of cases. The FDA has approved Gadobutrol for use in MRI scans, which supports its safety. However, if Gadobutrol leaks outside a vein during injection, it can cause irritation. Overall, Gadobutrol has a strong safety record based on many years of use and research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the use of Gadobutrol in enhanced MRI techniques for cervical cancer. Unlike standard MRI, which might not capture subtle changes during treatment, this method uses dynamic contrast-enhanced MRI (DCE-MRI) with Gadobutrol to potentially offer clearer, more detailed images. This could lead to better tracking of how the cancer responds to treatments and help doctors make more informed decisions. The hope is that this advanced imaging could improve early detection of treatment effects, ultimately leading to better outcomes for patients.

What evidence suggests that this DCE MRI technique is effective for cervical cancer imaging?

In this trial, participants will receive Gadobutrol as part of the DCE-MRI imaging process. Studies have shown that Gadobutrol effectively improves MRI images, producing clearer and more detailed pictures to help doctors see tumors more clearly. This contrast agent accurately identifies the presence of tumors, with a sensitivity range of about 59% to 98%, and their absence, with a specificity range of 75% to 100%. Gadobutrol requires a smaller injection amount, which helps create sharper images more quickly, facilitating informed treatment decisions by doctors. ^{6 7 8 9 10}

Who Is on the Research Team?

Oguz Akin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women aged 18 or older with gynecologic cancer who are about to receive standard pelvic MRI before treatment. Participants must be planning chemoradiation (for SA2b only), able to consent, and follow the study's schedule.

Inclusion Criteria

I am a woman over 18 with gynecologic cancer, planning to follow the study's treatment and visit schedule.

I am a healthy woman, 18 or older, and can give informed consent.

Exclusion Criteria

Women must not be breastfeeding

History of allergic reactions to gadolinium-based contrast agents (GBCAs)

Contraindications/risk factors to 3T MRI as per assessed by our departmental 'Comprehensive MRI Screening Questionnaire' and 'MRI Contrast Dye Questionnaire' (e.g. risk factors associated with magnetic field such as cardiac pacemakers, defibrillators or other devices as per standard institutional policy; and risk factors associated with GBCM such as diabetes, dialysis, breastfeeding)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline DCE-MRI

Participants undergo a baseline DCE-MRI scan to fine-tune parameters and test performance of reconstruction and quantification algorithms

1 day

1 visit (in-person)

Post-treatment DCE-MRI

Participants undergo a DCE-MRI scan 2 weeks after completion of standard of care treatment to assess repeatability and treatment-induced changes

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gadobutrol

Trial Overview The study tests a new DCE MRI technique using gadobutrol contrast against traditional MRI. It aims to produce clearer, more detailed images quickly, potentially improving tumor assessment and treatment decisions in gynecologic cancers.

How Is the Trial Designed?

Group I: DCE-MR images with Gadobutrol (GBCA) Experimental Treatment 2 Interventions

10 volunteers will undergo a single DCE-MRI of the normal cervix to fine-tune parameters and test the performance of reconstruction and quantification algorithms. Goldenangled radial LAVA data will be continuously acquired for 5 minutes and the contrast agent will be injected intravenously after 1 minute (same contrast agent and injection rate. 60 gynecologic cancer patients will be enrolled (inclusion criterion: newly diagnosed gynecologic cancer scheduled for standard of care pelvic MRI for staging). Data from 30 of the patients will be used to assess repeatability; DCE-MRI will be acquired at baseline and 2 weeks (+/- 3 days) after completion of standard of care treatment. Data from the other 30 patients will be used to document treatment induced changes in DCE-MRI; patients in this group will undergo DCE-MRI at baseline and repeated after 2 weeks (+/- 3 days) of completion of chemoradiation treatment.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

The standard treatment for locally advanced cervical cancer involves a combination of platinum-based chemotherapy, external beam radiotherapy (EBRT), and brachytherapy (BT), with MRI being the most effective imaging method for staging and evaluating treatment response.

This paper outlines the MRI-guided interventional radiotherapy (IRT) workflow at the authors' institution, providing a detailed pictorial guide to help radiologists implement this technique in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging in cervical cancer interventional radiotherapy (brachytherapy): a pictorial essay focused on radiologist management. Russo, L., Lancellotta, V., Miccò, M., et al.[2022]

The study involving 40 patients with stages IB2 and II cervical cancer demonstrated that pulsed dose rate image-guided brachytherapy (PDR-IGBT) after concurrent chemoradiotherapy (CRT) is a feasible and effective treatment, achieving a local control rate of 90% and overall survival of 100% over a median follow-up of 30 months.

While the treatment was generally well-tolerated, some patients experienced acute and chronic adverse events, with 12.5% experiencing grade 3 to 4 gastrointestinal issues, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concomitant Chemoradiotherapy With Image-guided Pulsed Dose Rate Brachytherapy as a Definitive Treatment Modality for Early-stage Cervical Cancer. Refaat, T., Castelain, B., Small, W., et al.[2021]

High-resolution endorectal magnetic resonance imaging (eMRI) improved the staging of cervical carcinoma in 39% of patients by identifying proximal vaginal involvement, which was not detected through standard examination methods.

The study found that tumors with bright signal characteristics on eMRI were associated with earlier disease stages, better hemoglobin levels, and higher rates of complete response to irradiation, suggesting that eMRI can provide valuable prognostic information to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Signal characteristics of tumors shown by high-resolution endorectal coil magnetic resonance imaging may predict outcome among patients with cervical carcinoma treated with irradiation. A preliminary study. Corn, BW., Schnall, MD., Milestone, B., et al.[2005]

In a study of 126 cervical cancer patients, 3D MRI-guided brachytherapy (IGBT) showed a trend towards improved local control and overall survival compared to 2D conventional brachytherapy (CBT), with local control rates of 93% after 1 year and 88% after 3 years.

The use of interstitial needles in IGBT allowed for higher doses to the high-risk clinical target volume while reducing radiation exposure to the bladder, resulting in decreased toxicity from 17% in the 2D cohort to 12% in the 3D cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of brachytherapy technique (2D versus 3D) on outcome following radiotherapy of cervical cancer. Derks, K., Steenhuijsen, JLG., van den Berg, HA., et al.[2022]

Endovaginal MRI (evMRI) using T2-weighted and ZOOM-diffusion-weighted imaging demonstrated high sensitivity (92.0%) and specificity (81.8%) for detecting stage Ia/Ib1 cervical cancer in a study of 57 patients, indicating its effectiveness in early cancer detection.

The imaging findings from evMRI led to changes in surgical management for approximately 39% of patients scheduled for radical vaginal trachelectomy, highlighting its potential impact on treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influencing surgical management in patients with carcinoma of the cervix using a T2- and ZOOM-diffusion-weighted endovaginal MRI technique. Downey, K., Jafar, M., Attygalle, AD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5009507/

case report with emphasis on early diagnosis - PMC Gadobutrol provides higher lesion conspicuity and enhances lesion detection in meningeal metastasis compared with gadopentetate dimeglumine.

2. journals.lww.com journals.lww.com/investigativeradiology/fulltext/2024/05000/clinical_efficacy_of_gadobutrol__review_of_over_25.1.aspx

Clinical Efficacy of Gadobutrol: Review of Over 25 Years ... The overall sensitivity ranged from 58.7% to 97.8%, and specificity ranged from 75% to 100% (Table 2; Fig. 2). The clinical issues comprised a wide spectrum of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6153968/

Gadobutrol: A Review in Contrast-Enhanced MRI and MRA The higher concentration of gadobutrol reduces its injection volume by 50%, providing a narrower bolus and thereby, improving dynamic image ...

4. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/radiol.222612

Efficacy and Safety of Half-Dose Gadopiclenol versus Full- ... Gadopiclenol at half the standard dose for contrast-enhanced body MRI had comparable efficacy with gadobutrol at the full standard dose.

5. ajronline.org ajronline.org/doi/10.2214/AJR.21.25924

Clinical Efficacy of Reduced-Dose Gadobutrol Versus ... A 25% reduced dose of gadobutrol showed noninferior efficacy versus standard-dose gadoterate for contrast-enhanced brain MRI and warrants particular ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/201277s000lbl.pdf

Gadavist (gadobutrol) injection - accessdata.fda.gov Extravasation into tissues during Gadavist administration may result in moderate irritation. Avoid intramuscular administration of Gadavist [see Nonclinical ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38426761/

Clinical Safety of Gadobutrol: Review of Over 25 Years ... Drug-related adverse events (AEs) were reported in 3.4% and serious AEs in <0.1% of patients.

8. pdf.hres.ca pdf.hres.ca/dpd_pm/00076064.PDF

GADOVIST® 1.0 (gadobutrol injection) The overall safety profile of GADOVIST 1.0 is based on data from more than 6,300 patients in clinical trials. The most frequently observed ...

9. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/g/gadovistinj.pdf

GADOVIST® 1.0 (1.0 mmol/mL) Solution for Intravenous ... Serious, life-threatening and fatal cases, primarily with neurological reactions (e.g. coma, encephalopathy, seizures), have been reported with intrathecal use.

10. mayoclinic.org mayoclinic.org/drugs-supplements/gadobutrol-intravenous-route/description/drg-20074828

Gadobutrol (intravenous route) - Side effects & uses Gadobutrol injection is a magnetic resonance imaging (MRI) contrast agent that is used to help create a clear picture of the body during an MRI scan.