AGuIX Gadolinium-based Nanoparticles in Combination With Chemoradiation and Brachytherapy

NCT ID: NCT03308604

Last Updated: 2021-07-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-17
• Study Completion Date: 2024-05-31

Brief Summary

This is a phase 1 clinical trial evaluating the safety, tolerability of escalating doses of AGuIX-NP in combination with radiation and cisplatin in patients with locally advanced cervical cancer. Dose escalation will be conducted using the modified toxicity probability interval (mTPI) method.

Three dose levels of intravenous AGuIX nanoparticles will be explored: 20mg/kg (level -1), 30 mg/kg (level 1) and 50 mg/kg (level 2).

Conditions

Gynecologic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with locally advanced cervical cancer

Group Type: EXPERIMENTAL

Polysiloxane Gd-Chelates based nanoparticles (AGuIX)

Intervention Type: DRUG

Three intravenous injections of AGuIX will be delivered.

The first injection of AGuIX will be delivered intravenously the 1st day and the 11th day of EBRT. The first injection will be preceded with an MRI (unenhanced T1 and T2 sequences) then followed with another MRI performed 4 hours later, to monitor tumor uptake.

Irradiation will be performed after the second MRI.

The second injection will be followed by an MRI 4 hours later.

The third injection will be delivered intravenously the day of the brachytherapy procedure. Intravenous hydration will be performed during all brachytherapy courses to ensure AGuIX clearance.

Up to three dose levels may be explored: 20mg/kg (level -1), 30 mg/kg (level 1) and 50 mg/kg (level 2). The starting dose level will be 30mg/kg.

External beam radiotherapy (EBRT)

Intervention Type: RADIATION

to the pelvis, with intensity modulated technique: 45 Gy in 5 weeks, with integrated boost to 55 - 57.5 Gy in case of macroscopic lymph node metastases

Uterovaginal brachytherapy

Intervention Type: RADIATION

15 Gy (maximal interval between EBRT and brachytherapy: 14 days).

Chemotherapy (cisplatin)

Intervention Type: DRUG

Concomitant weekly intravenous cisplatin 40 mg/m2 will be delivered (total 5 cycles).

Interventions

Polysiloxane Gd-Chelates based nanoparticles (AGuIX)

Three intravenous injections of AGuIX will be delivered.

The first injection of AGuIX will be delivered intravenously the 1st day and the 11th day of EBRT. The first injection will be preceded with an MRI (unenhanced T1 and T2 sequences) then followed with another MRI performed 4 hours later, to monitor tumor uptake.

Irradiation will be performed after the second MRI.

The second injection will be followed by an MRI 4 hours later.

The third injection will be delivered intravenously the day of the brachytherapy procedure. Intravenous hydration will be performed during all brachytherapy courses to ensure AGuIX clearance.

Up to three dose levels may be explored: 20mg/kg (level -1), 30 mg/kg (level 1) and 50 mg/kg (level 2). The starting dose level will be 30mg/kg.

Intervention Type: DRUG

External beam radiotherapy (EBRT)

to the pelvis, with intensity modulated technique: 45 Gy in 5 weeks, with integrated boost to 55 - 57.5 Gy in case of macroscopic lymph node metastases

Intervention Type: RADIATION

Uterovaginal brachytherapy

15 Gy (maximal interval between EBRT and brachytherapy: 14 days).

Intervention Type: RADIATION

Chemotherapy (cisplatin)

Concomitant weekly intravenous cisplatin 40 mg/m2 will be delivered (total 5 cycles).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with histologically confirmed cancer of the uterine cervix: squamous cell carcinoma or adenocarcinoma stage IB2-IVA according to the International Federation of Gynecology and Obstetrics classification, regardless of the pelvic lymph node stage. No evidence of metastatic disease. Primary staging should include: clinical examination, Pelvic MRI and 18-FDG PET. A coelioscopic para-aortic lymph node staging should be done in patients without para-aortic lymph node uptake to guide radiotherapy fields in the situation of pelvic lymph node metastases. If there is no pelvic lymph node metastases, para-aortic lymph node dissection is optional.

2. ECOG performance status 0-1.

3. Age between 18 - 70 years.

4. Neutrophils > 2000/mm^3.

5. Hemoglobin > 9 g/L after transfusion if necessary.

6. Platelets > 100,000/mm^3.

7. Creatinine < 1.5 upper limit of normal or calculated creatinine clearance (Cockcroft-Gault Formula) ≥ 60 mL/min.

8. Liver function (GOT, GPT, alkaline phosphatase and bilirubin) < 1.5 upper limit of normal.

9. Cardiovascular: no clinically relevant cardiovascular disease, no congestive heart failure, no symptomatic coronary artery disease, no poorly controlled cardiac arrhythmia, no myocardial infarction within the past year.

10. Gastrointestinal: no active inflammatory bowel disease, no lack of physical integrity of the upper gastrointestinal tract, no malabsorption syndrome.

11. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of treatment.

12. Proteinuria < 2 g/L (200mg/dL) and creatinine clearance ≥ 60 mL/min.

13. Signed informed consent after informing the patient.

14. Patient affiliated to a social security regimen or beneficiary of the same.

2. History of cancer other than basal cell carcinoma within five past years.

3. Prior treatment with radiotherapy, chemotherapy, targeted therapy or immune therapy for cervical cancer or for any cancer within five past years.

4. Prior pelvic radiotherapy or prior surgical treatment for cervical cancer (excluding diagnostic conisation).

5. Pregnancy or breastfeeding.

6. Obesity (Body Mass Index > 30).

7. History of prior or current psychiatric illness.

8. Nephropathy, regardless of the grade.

9. Peripheral neuropathy ≥ grade 2.

10. Patients with pre-existing hearing impairments.

11. Active infection or other serious underlying pathology that could prevent the patient from receiving the treatment (especially liver or heart conditions).

12. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.

13. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

14. Inclusion in another clinical trial protocol with an experimental molecule (during this study or within 5 years prior to enrollment).

15. Unable to undergo the follow-up required by study for geographical, social or psychological reasons.

16. Contra-indication for Magnetic Resonance Imaging enhanced with gadolinium and/or any contra-indication to the use of cisplatin.

17. History of allergic reaction to cisplatin or other platinum containing compounds.

18. Concurrent administration of yellow fever vaccine.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute, France

OTHER_GOV

Sponsor Role: collaborator

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cyrus CHARGARI, MD

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Locations

Centre Hospitalier Lyon Sud

Pierre-Bénite, Rhône, France

Site Status: NOT_YET_RECRUITING

Gustave Roussy

Villejuif, Val De Marne, France

Site Status: RECRUITING

Countries

France

Central Contacts

Cyrus CHARGARI, MD

Role: CONTACT

cyrus.chargari@gustaveroussy.fr

+33 (0) 1 42 11 42 11 ext. 33 65

Matthieu TEXIER

Role: CONTACT

matthieu.texier@gustaveroussy.fr

+33 (0) 1 42 11 62 52

Facility Contacts

Ionela CARAIVAN, MD

Role: primary

ionela.caraivan@chu-lyon.fr

+33 (0) 4 78 86 42 60

Cyrus CHARGARI, MD

Role: primary

cyrus.chargari@gustaveroussy.fr

+33 (0) 1 42 11 42 11 ext. 33 65

Matthieu TEXIER

Role: backup

matthieu.texier@gustaveroussy.fr

+33 (0) 1 42 11 62 52

References

Maury P, Mondini M, Chargari C, Darricau A, Shahin M, Ammari S, Bockel S, Genestie C, Wu TD, Lux F, Tillement O, Lacombe S, Deutsch E, Robert C, Porcel E. Clinical transfer of AGuIX(R)-based radiation treatments for locally advanced cervical cancer: MR quantification and in vitro insights in the NANOCOL clinical trial framework. Nanomedicine. 2023 Jun;50:102676. doi: 10.1016/j.nano.2023.102676. Epub 2023 Apr 20.

Reference Type: DERIVED

PMID: 37084803 (View on PubMed)

Other Identifiers

2016/2508

Identifier Type: OTHER

Identifier Source: secondary_id

2016-005127-83

Identifier Type: -

Identifier Source: org_study_id