Evaluation of Concomitant Chemo-radiotherapy With Cisplatine vs Gemcitabin in Locally Advanced Cervicouterine Cancer (MICHELE)

National Institute of Cancerología

Status and phase: Enrolling; Phase 3

Conditions: Chemo-radiotherapy; Gemcitabine; Locally Advanced Cervical Cancer

Treatments: Drug: Cisplatin; Drug: Gemcitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT06156514

(018/066/ICI) (CEI/1308/18).

Details and patient eligibility

About

The purpose of this phase III clinical trial, is to evaluate the efficacy and safety of concomitant chemo-radiotherapy with Cisplatin vs Gemcitabine as the first line of treatment in patients with locally advanced cervical cancer, with comorbidities and preserved renal function.

Full description

This is a phase III clinical trial, open, randomized 1: 1, controlled, noninferiority, in a single hospital center. This study will include 564 patients with the diagnosis of malignant tumors of epithelial origin of the cervix.

Patients will be randomized 1: 1, arm "A" (experimental) to receive concomitant chemotherapy based on gemcitabine at 300 mg / m2 weekly and Arm "B" (control) to receive cisplatin 40 mg / m2 weekly, both arms with RT 50.4 Gy in 5 weeks plus 30Gy brachytherapy at the end of the concomitance. These patients will be treated in the gynecology-oncology service, candidates for chemo-radiotherapy, it is intended that the recruitment of patients be done in the first 48 months, with a follow-up of 3 years. It is intended to include 3 patients per month, until the total sample is completed in four years. The study is divided into three phases, the first of QT / RT concomitant with gemcitabine or cisplatin depending on the randomized arm; with an approximate duration of 1.5 months with a weekly visit, the second phase is brachytherapy in both arms which lasts from 2 to 7 days, and finally the follow-up phase which lasts for 3 years with a visit every 3 months. In each of the visits we will evaluate the safety of the medication; evaluating adverse events, including laboratory abnormalities as well as acute and chronic toxicity, with the classification according to the common toxicity criteria (CTCAE v4.03) and the efficacy will obtain proportions of clinical and imaging response (TC and / or PET-CT) with the criteria of RECIST v1.1 and / or PERCIST 1.0.

Patient numbers to include. This study will include 140 patients. Test drug, dosage, mode of administration: Gemcitabine at 300 mg / m2 weekly intravenous administration.

Duration of the study 9 years.

Enrollment: 140 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Singed informed consent.

• Women with Age ≥ 18 years.

  1. -In women of childbearing age it should be documented: a) negative pregnancy test in serum at the beginning of the study (14 days before the start of QT-RT); b) Accept the use of some method of contraception approved by your attending physician during the study and 12 weeks after the treatment has ended.
  2. -In postmenopausal women (surgical or natural menopause) at least one of the following parameters must be met for inclusion.

• Previous bilateral oophorectomy

• Age ≥ 60 years

• Age <60 years and amenorrhea for at least 12 months and levels of follicle stimulating hormone and estradiol within postmenopausal interval parameters.

• Diagnosis of CaCu EC IB2 mg/dl With histological confirmation (epidermoid, adenocarcinoma or adenoescamoso).

• Patients who are candidates for treatment with concomitant QT / RT.

• ECOG 0-2.

• Measurable disease by CT scan and magnetic resonance imaging of the pelvis according to the RECIST criteria v1.1

• No previous treatment.

• Creatinine clearance ≥ 60 ml / min calculated by the CKD-EPI formula.

• Patients with adequate hematological and hepatic functioning, defined by the following parameters:

  1. Hb equal to or greater than 10g /l. (Transfusion prior to treatment is allowed to reach this level of hemoglobin).
  2. Leukocytes greater than or equal to 4000 / mm3.
  3. Platelets equal to or greater than 100,000mm3.
  4. Total bilirubin ≤1.5 times the upper limit of normal (ULN) and. Transaminases less than 1.5 times the LSN

• Patients with a prior diagnosis of the following comorbidities:

  • Diabetes mellitus type 2, which has: fasting serum glucose <250 mg/dl.
  • Systemic arterial hypertension G1 or G2 according to CTCAE v4.03
  • Child Pugh A liver disease
  • Cardiovascular diseases such as: Ischemic heart disease undergoing asymptomatic treatment, without clinical data of stable or unstable angina or for acute myocardial infarction.
  • Compensated heart failure in functional class I of the New York Heart Association.
  • Systemic Lupus Erythematosus with mild or inactive lupus activity (less than or equal to 4 points according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Exclusion criteria

• Patients with a second neoplasm.
• Pregnant or lactating patients.
• Patients with small cell and / or neuroendocrine CaCu.
• Patients with impaired renal function with a GFR <or equal to 60ml / min calculated by the CKD-EPI formula
• Patients with a history of active TB (TB)
• Patients with a history of Human Immunodeficiency Virus (HIV) infection
• Patients with vesico-vaginal or vesicorectal fistulas at diagnosis
• Concomitant treatment with another experimental drug. Social, family or geographical conditions that suggest a poor attachment to the study

Criteria Interruption of Treatment (Withdrawal of patients)

A patient will be discontinued from the study under the following circumstances:

• Evidence of disease progression.
• If treating physician considers that a change of therapy may benefit the patient.
• If patient withdrew consent
• Due to unmanageable toxicity By pregnancy or if the patient does not wish to continue using the contraceptive methods indicated by the attending physician

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

A (Gemcitanine)

Experimental group

Description:

To receive concomitant chemotherapy based on gemcitabine at 300 mg / m2 weekly

Treatment:

Drug: Gemcitabine

B (Cisplatin)

Active Comparator group

Description:

To receive concomitant chemotherapy based on cisplatin 40 mg / m2 weekly

Treatment:

Drug: Cisplatin