Induction Chemotherapy Followed by Standard Therapy in Cervical Cancer With Aortic Lymph Node Spread (ONCOCOL01)

September 18, 2023 updated by: University Hospital, Toulouse

Phase III Study Comparing Neoadjuvant Chemotherapy With Carboplatin and Paclitaxel Followed by Standard Therapy, With Standard Therapy Alone in Women With Cervical Cancer and Para Aortic Positive Lymph Node.

The main objective of this study is to determine whether neoadjuvant chemotherapy with Carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields improves overall survival rates compared to standard therapy alone in women with cervical cancer with paraaortic lymph node involvement.

Women in the experimental arm will receive neoadjuvant chemotherapy with carboplatin and paclitaxel every 21 days during 3 cycles followed by standard therapy with extended field external radiation therapy and concomitant chemotherapy. Women in the control arm will receive standard therapy with extended field external radiation therapy and concomitant chemotherapy.

310 patients will be recruited during 4.5 years, with 3 years of follow up period.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The survival outcome of patients with carcinoma of the cervix and positive paraaortic lymph node is poor and the potential benefit of neoadjuvant chemotherapy before extended field chemoradiotherapy has never been assessed.

Paraaortic nodal spread in cervical cancer is a blind spot in the management of cervical cancer. It is necessary to evaluate additional treatment.

While the presence of paraaortic nodal metastases often indicates occult systemic disease, the investigators continue to treat them as a loco-regional disease.

Using neoadjuvant chemotherapy, improvement of overall survival rates is expected in women with cervical cancer and para-aortic positive lymphadenopathy without increasing the incidence of further toxicity.

The propose is to determine whether neoadjuvant chemotherapy with Carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields improves overall survival rates compared to standard therapy alone in women with cervical cancer with paraaortic lymph node involvement.

Secondary objectives will be to compare progression free survival, acute and long term toxicities, patterns of disease recurrence and patient quality of life between arms This is a phase III, multicenter, randomized, open label study, recruiting 310 patients during 4.5 years, with 3 years of follow up period.

Two groups will be compared : neoadjuvant chemotherapy with Carboplatin and paclitaxel plus standard cisplatin-based chemoradiation with extended fields, versus standard therapy alone.

Randomization will be stratified according to International federation of gynecology and obstetrics stages at diagnosis (IB1, IB2, IIA versus IIB-IVA), the size of positive para aortic lymphadenopathy and the number of node involved and will be balanced by blocks.

Women in the experimental arm will receive neoadjuvant chemotherapy with carboplatin and paclitaxel followed by standard therapy with extended field external radiation therapy and concomitant chemotherapy then intracavitary brachytherapy, alone or prior to surgery, depending on response to treatment according to the current guidelines.

Women in the control arm will receive standard therapy with extended field external radiation therapy and concomitant chemotherapy then brachytherapy, alone or prior to surgery, depending on response to treatment according to the current guidelines.

Follow up will be the same between arms. But in experimental arm, during treatment phase, a clinical examination and biological assessment will be performed before each cycle of neoadjuvant chemotherapy. Therefore, at the end of neoadjuvant treatment, just before standard treatment magnetic resonance imaging and positron emission tomography-computed tomography will be performed.

Then, all Participants will be followed every 4 months until 2 years after randomization and every 6 months during the third year according to current follow-up guideline for cervical cancer. Disease response and disease progression will be assessed using clinical examination. Quality of life will be estimated at baseline, at the end of neoadjuvant chemotherapy, before intracavitary brachytherapy and at each follow-up visit until 3 years after randomization.

Study Type

Interventional

Enrollment (Estimated)

310

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France, 33000
      • Clermont-Ferrand, France, 63011
      • Créteil, France, 94000
      • Marseille, France, 13009
      • Pierre-Bénite, France, 69495
      • Poitiers, France, 86000
      • Saint-Herblain, France, 44805
      • Saint-Pierre, France, 97448
      • Toulouse, France
      • Toulouse, France, 31059
      • Tours, France, 37044

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women with histologically proven invasive carcinoma of the uterine cervix and para aortic lymphadenopathy determined by either a positive positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose integrated with computed tomography or if negative positron emission tomography computed tomography based on histological examination of paraaortic lymph node dissection.
  • Performance status Eastern Cooperative Oncology Group 0-2
  • Stage International Federation of Gynecology and Obstetrics IB1 to IVA at diagnosis with para-aortic lymph node involvement
  • Adenocarcinoma or squamous cell carcinoma or adenosquamous carcinoma
  • Adequate renal function (creatinine clearance ≥60 mL/min)
  • Adequate hepatic function (bilirubin <1.5 times normal and Serum Glutamooxaloacetate Transferase < 3 times normal)
  • Adequate hematopoietic function Platelet count > 100x10 9/l and Absolute neutrophil count > 1.5X10 9/l)
  • Written Informed consent for participation

Exclusion Criteria:

  • Stage Federation of Gynecology and Obstetrics IVB at diagnosis
  • Others histologies than adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma.
  • Women who receive any prior chemotherapy for her cervical cancer
  • Pregnant or lactating women
  • Prior ( within the last 5 years) malignancies other than non-melanoma skin cancer
  • Inadequate renal, hepatic or hematopoietic function (Cf previously)
  • Cardiovascular pathology New York Heart Association II or more
  • Pre-existing Peripheral neuropathy Common toxicity Criteria grade ≥ 2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant chemotherapy+standard therapy
neoadjuvant chemotherapy with carboplatin aera Under curve 5 and paclitaxel 175 mg/m² every 21 days during 3 cycles followed by standard therapy with extended field external radiotherapy and concomitant chemotherapy (Cisplatin 40mg/m2 weekly)
Drug: Carboplatin
carboplatin aera Under curve 5 on day 1, every 21 days during 3 cycles
Other Names:
  • Carbo
Drug: Paclitaxel
paclitaxel 175 mg/m² on day 1, every 21 days during 3 cycles
Other Names:
  • Taxol
Drug: Cisplatin
Cisplatin 40mg/m² given once a week during 5 weeks
Other Names:
  • Platinol
Radiation: Radiotherapy
45 gray to the pelvis and para aortic area over 5 weeks + intracavitary brachytherapy alone or prior to surgery, depending on response to treatment according to the current guidelines
Other Names:
  • radiation therapy
Active Comparator: standard therapy alone
standard therapy with extended field external radiotherapy and concomitant chemotherapy (Cisplatin 40mg/m2 weekly)
Drug: Cisplatin
Cisplatin 40mg/m² given once a week during 5 weeks
Other Names:
  • Platinol
Radiation: Radiotherapy
45 gray to the pelvis and para aortic area over 5 weeks + intracavitary brachytherapy alone or prior to surgery, depending on response to treatment according to the current guidelines
Other Names:
  • radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 3 years
time between random assignment and death resulting from any cause
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: fron date of randomization until the date of first documented progression or date of death from any cause, assessed up to 3 years
time from randomization to first documentation of disease progression or death due to any cause.
fron date of randomization until the date of first documented progression or date of death from any cause, assessed up to 3 years
adverse events
Time Frame: 3 years
classified using the Common Terminology Criteria for Adverse Events and coded using Medical Dictionary for Regulatory Activities dictionary Pattern of disease recurrence will include locoregional recurrence and distant metastasis
3 years
quality of life questionnaire C30 and CX24
Time Frame: 3 years
assessed using the European Organization for Research and Treatment Quality of Life Questionnaire C30 and CX24, all subscales responses will be converted to 0 to 100 scales according to European Organization for Research and Treatment guidelines
3 years
patterns of first relapse
Time Frame: 3 years
location of relapse or metastasis by magnetic resonance imaging
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Toulouse

Collaborators

Institut Claudius Regaud

Investigators

  • Principal Investigator: Stéphanie MOTTON, MD, University Hospital, Toulouse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 17, 2020

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

April 16, 2018

First Submitted That Met QC Criteria

May 22, 2018

First Posted (Actual)

May 23, 2018

Study Record Updates

Last Update Posted (Actual)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 18, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/17/0213

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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