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AGuIX Gadolinium-based Nanoparticles in Combination With Chemoradiation and Brachytherapy (NANOCOL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03308604
Recruitment Status : Recruiting
First Posted : October 12, 2017
Last Update Posted : July 13, 2018
Sponsor:
Collaborator:
National Cancer Institute, France
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

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).


Condition or disease Intervention/treatment Phase
Gynecologic Cancer Drug: Polysiloxane Gd-Chelates based nanoparticles (AGuIX) Radiation: External beam radiotherapy (EBRT) Radiation: Uterovaginal brachytherapy Drug: Chemotherapy (cisplatin) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of AGuIX Gadolinium-based Nanoparticles in Combination With Chemoradiation and Brachytherapy in Locally Advanced Cervical Cancer
Actual Study Start Date : May 17, 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : May 2021

Arm Intervention/treatment
Experimental: Patients with locally advanced cervical cancer Drug: 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.


Radiation: 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

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

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




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 8 weeks after inclusion ]
  2. Recommended Phase 2 Dose (RP2D) [ Time Frame: 8 weeks after inclusion ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Gynecologic Cancer
Accepts Healthy Volunteers:   No
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, 18-FDG PET and Coelioscopic para-aortic lymph node staging
  2. ECOG performance status 0-1.
  3. Age between 18 - 70 years.
  4. Neutrophils> 2000 / mm3
  5. Hemoglobin> 9 g / l after transfusion if necessary.
  6. Platelets> 100,000 / mm3
  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

Exclusion Criteria:

  1. Other histological types of cervical cancer than those listed in the inclusion criteria or stage IVB.
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03308604


Contacts
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Contact: CHARGARI Cyrus, MD 0142113365 ext +33 cyrus.chargari@gustaveroussy.fr
Contact: PAOLETTI Xavier, MD 0142116564 ext +33 xavier.paoletti@gustaveroussy.fr

Locations
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France
Gustave Roussy Recruiting
Villejuif, Val De Marne, France, 94805
Contact: CHARGARI Cyrus, MD    0142113365 ext +33    cyrus.chargari@gustaveroussy.fr   
Contact: PAOLETTI Xavier, MD    0142116564 ext +33    xavier.paoletti@gustaveroussy.fr   
Principal Investigator: CHARGARI Cyrus, MD         
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
National Cancer Institute, France
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Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT03308604    
Other Study ID Numbers: 2016-005127-83
2016/2508 ( Other Identifier: CSET number )
First Posted: October 12, 2017    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cisplatin
Antineoplastic Agents