Evaluate Efficacy of the Association Nimotuzumab(HR3) /Cisplatin-Vinorelbine on Patients With Cervical Carcinom

NCT ID: NCT03413579

Last Updated: 2021-08-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-11-30

Study Completion Date

2021-02-28

Brief Summary

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The objective of the present study is to estimate the overall survival of patients with cervical cancer after the administration of monoclonal antibody (mAb) Nimotuzumab (hR3) in combination with chemotherapy of first intention. Patients will be randomized in two parallel treatment groups. The first group will receive a dose of 200 mg of monoclonal antibody anti-hR3 (weekly during 18 weeks), combined with a chemotherapy (6 cycles, every 21 days of Cisplatin 70mg/m2, Vinorelbine 60 mg/m2 (Per Os) at D1 and D8 and then 80mg / m2. The second group will receive a placebo in combination with the same chemotherapy regimen as the first group.

At the end of the first intention chemotherapy treatment, a dose of maintenance of Nimotuzumab will be administered at the dose of 200mg every 14 days until progression. A second chemotherapy in the second intention is proposed, this one is based on Carboplatin ( CBP) in an AUC (area under curve) of 6, and Paclitaxel (Txl) in 175 mg / m2 / BSA (body surface area ) in drip of 3 hours, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a limit of toxicity or an ECOG (Eastern Cooperative Oncology Group) status superior to 3, appears.

Detailed Description

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The objective of the present study is to assess the overall survival of patients after administration of Nimotuzumab hR3 monoclonal antibodies (combined with a chemotherapy) in the treatment of patients with cervix epithelial tumors as first-line treatment.

The patients included will be divided into two treatment groups. The first group receive a 200 mg dose of hR3 monoclonal antibody (weekly for 18 weeks), and chemotherapy (6 cycles, every 21 days: Cisplatin (CDDP) 70 mg / m2 on day 1, Vinorelbine 60 mg / m2 on day 1 and day 8) and then 80mg / m2. The second group receive a placebo in addition to the listed chemotherapy.

After the first line , a 200mg dose of hR3 monoclonal antibodies will be given every 14 days until progress.

A second -line chemotherapy is proposed, this is based on Carboplatin (CBP) at AUC of 6, and Paclitaxel (Txl) 175 mg / m2 / SC as 3 hour infusion, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a toxicity limit or an ECOG status greater than 3 appears.

The survival overall will be considered as the main variable of the response and survival without progression from the antitumor response, the toxicity assessment and the quality of life will be the secondary variables. In addition, the effects may arise during treatment will be identified, and tumor biopsy markers such as, EGF-R and HPV will be determined and those of p53, Ki67 and Bcl-2 by immunohistochemistry (IHC).

It is expected to achieve a difference in survival between the treatment groups of 6.5 vs 10.5 months (0.278 vs 0.62) in favor of the group with mAb hR3.

Conditions

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Cervical Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Nimotuzumab

Injection of 200 mg of Nimotuzumab (weekly during 18 weeks), in combination with chemotherapy (6 cycles, every 21 days: 70 mg / m2 Cisplatin and Vinorelbine 60 mg / m2 (Per Os) at day 1 and day 8.

The objective of the present study is to assess the overall survival of patients after administration of Nimotuzumab hR3 monoclonal antibodies (combined with a chemotherapy) in the treatment of patients with cervix epithelial tumors as first-line treatment.

After the first line , a 200mg dose of hR3 monoclonal antibodies will be given every 14 days until progress.

A second -line chemotherapy is proposed, this is based on Carboplatin (CBP) at AUC of 6, and Paclitaxel (Txl) 175 mg / m2 / SC as 3 hour infusion, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a toxicity limit or an ECOG status greater than 3 appears.

Group Type EXPERIMENTAL

Nimotuzumab ( h-R3)

Intervention Type BIOLOGICAL

Humanized monoclonal antibody

Placebo

Injection of the Placebo in the same procedures (weekly during 18 weeks), in combination with chemotherapy (6 cycles, every 21 days: 70 mg / m2 Cisplatin and Vinorelbine 60 mg / m2 (Per Os) at day 1 and day 8.

After the first line , a 200mg dose of hR3 monoclonal antibodies will be given every 14 days until progress.

A second -line chemotherapy is proposed, this is based on Carboplatin (CBP) at AUC of 6, and Paclitaxel (Txl) 175 mg / m2 / SC as 3 hour infusion, every 3 weeks, concomitant with the administration of hR3, every 14 days, until a toxicity limit or an ECOG status greater than 3 appears.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Interventions

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Nimotuzumab ( h-R3)

Humanized monoclonal antibody

Intervention Type BIOLOGICAL

Placebo

Intervention Type OTHER

Other Intervention Names

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CIMAHOPE

Eligibility Criteria

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Inclusion Criteria

* Patients aged between 18 to 75, including both limits.
* Patients who give their written consent to participate to the study.
* Chemonaive patients with local cervical cancer and / or persistent or recurrent metastatic disease with measurable disease (RECIST criteria) by a physical examination (scanner or MRI).

A confirmation by biopsy is necessary in case there is a single lesion less than 2 cm.

* Patients who had pelvic CT + radiotherapy may also be included in the study (concomitant chemotherapy as a radiotherapy stabilizer).
* Patients having a histopathological report: epidermoid carcinoma, adenocarcinoma, adenosquamous carcinoma and / or clear cells carcinoma.
* Patients with an ECOG score between 0-2
* Patients with a life expectancy greater than six months.
* Patients with Left Ventricular Ejection Fraction (LVEF) ≥50%, through Echocardiography.
* Patients with normal function of organs and bone marrow, defined by the following parameters:

* Haemoglobin ≥ 9 g / dL
* White Blood cell ≥ 4000 /mm3
* Absolute neutrophil count≥ 1500 /mm3
* Platelet count≥ 100000 /mm3
* Total bilirubin up to 1.5 the upper limit of normal (ULN)
* Albumin ≥ 2 g/dL (3,5 - 5,0 g /dl)
* Serum Glutamopyruvate Transférase (SGPT) and SErum Glutamooxaloacetate Transferase (SGTO) \< or = 2.5 ULN
* Serum creatinine within the normal limits and the calculation of glomerular filtration according to Cockcroft formula ≥ 60ml and according to MDRD formula for patients whose age is 70 years ≥ 60ml . Glomerular filtration will be performed only on clinical discretion for patients suspected to have a kidney problem. (The normal laboratory values will be appropriate to the techniques and equipment used in the place where they are done).
* The determination or expression of EGF-R (epidermal growth factor receptor), p53, Ki67 and Bcl-2 by immuno-histochemistry in the primary tumor before treatment integrated in a paraffin block.

The results are not an inclusion criterion, but will be evaluated as an indicator of prognostic response in the final assessment.

Exclusion Criteria

* Pregnant or breastfeeding patients
* Patients with small cells and / or neuroendocrine cervical cancer.
* Patients receiving another onco-specific drug, for other clinical trial,
* Patients with a history of allergy attributed to chemical or biological compounds similar to the monoclonal antibody being evaluated or to chemotherapeutic agents.
* Patients having uncontrolled intercurrent diseases, including active infections, symptomatic congestive heart failure , unstable angina, cardiac arrhythmia, decompensated diabetes, uncontrolled hypertension and psychiatric disorders.
* Patients having a second tumor . Excepting for those receiving appropriate therapy for skin cancer (basal or squamous)
* Previous or concomitant malignancy with exception for non-melanoma skin carcinomas
* Patients having special conditions or circumstances that could significantly limit the complete follow up of the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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El Kendi Pharmaceuticals Manufacturing Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mohamed MECHETI, MD.

Role: STUDY_DIRECTOR

El Kendi, Part of MS Pharma, Manufacturing Company

Locations

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Centre Pierre et Marie Curie (CPMC)

Algiers, , Algeria

Site Status

CAC Annaba

Annaba, , Algeria

Site Status

CAC Batna

Batna City, , Algeria

Site Status

CHU Frantz Fanon

Blida, , Algeria

Site Status

CHU Sidi Belloua

Tizi Ouzou, , Algeria

Site Status

Countries

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Algeria

Other Identifiers

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CIMA-I3-05D143-01

Identifier Type: -

Identifier Source: org_study_id

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