Chemotherapy and Pelvic Hypofractionated Radiation Followed by Surgery Cervical Cancer

Phase II Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With Standard Fractionated Compared to Hypofractionated Followed by Surgery for Patients With Locally Advanced Cervical Cancer.

The purpose of the study is to evaluate the role of hypofractionated in the treatment of locally advanced cervical cancer. The study will be conducted in Honduras and Mexico, and patients will be randomized to a standard fraction (45 Gy in 25 fractions) or hypofractionated (37.5Gy in 15 fractions) followed by surgery. Patients will receive weekly cisplatin with their treatments at 40 mg/m2. Response rate, survival, and toxicity will be evaluated.

Study Overview

• Status: Recruiting
• Conditions: Cervix Cancer
• Intervention / Treatment: Radiation: Standard radiotherapy; Procedure: Radical hysterectomy; Radiation: hypofractionated radiotherapy

Detailed Description

Toxicity will be assessed six times during this study. In addition to the primary endpoint of patient-reported gastrointestinal toxicity, a broad range of other toxicities will be comprehensively evaluated, including urinary, hematologic and dermatologic, this data will allow to determining the effect of hypofractionated radiation therapy on each of these aspects of toxicity from pelvic radiation. Additionally, will be recognized that it is possible to advance in the understanding of the clinical risk and benefits of hypofractionation.

The primary endpoint will be acute gastrointestinal toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria.

In total, evaluating toxicity in different time points will allow determining if hypofractionation is secure concerning acute and late toxicity, that would enable to offer an optional treatment to this kind of patient. Chronic gastrointestinal toxicity from radiation continues to increase rapidly over two years, and then the rate of developing new toxicities slows. As a result, the majority of chronic radiation-induced gastrointestinal toxicity by evaluating toxicity two years after completion of radiotherapy is going to be identified.

Quality of life (QOL) will be evaluated using EORTC QLQ-CX24 and EORTC QLQ-C30, both of which have been validated and available in Mexican Spanish.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lennt N Gallardo-Alvarado, MD, Msc; Phone Number: +521553702118; Email: dra.ngallardo@yahoo.com
• Study Contact Backup: Name: David F Cantu-de Leon, MD, MSC, PhD; Phone Number: +5215537093156; Email: dfcantu@gmail.com

Study Locations

• Mexico
  • Mexico City, Mexico, 14080
    • Recruiting
    • Instituto Nacional de Cancerologia
    • Contact: David F Cantu de Leon, MD, PhD; Phone Number: 21016 525556280400; Email: dfcantu@gmail.com
    • Contact: Lenny N Gallardo-Alvarado, Md, MSc; Phone Number: 37000 525556280400; Email: dra.ngallardo@yahoo.com
  • Tlalpan
    • Mexico City, Tlalpan, Mexico, 14080
      • Active, not recruiting
      • David Cantu de Leon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IIB squamous, adenosquamous or adenocarcinoma of cervical with no disease outside of the pelvis by via ultrasound.
• No distant metastasis via chest X-ray.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Age 18
• complete blood count (CBC)/differential obtained 14 days before study entry with adequate bone marrow function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mim3
• Platelets 100,000 cells/mim3
• Hemoglobin 8.0 g/dl
• White blood count 4000 cell/m3
• An adequate renal function defined as follows:
• Serum creatinine 1.5 mg/dl within 14 days before study entry
• Patients with known HIV positive must have a cluster of differentiation 4 (CD4) T lymphocytes count be 350 cells/mm3 within 14 days prior to study entry (note, however, that HIV testing is not required for entry into this protocol). Excluding HIV positive patients with invasive cervical cancer and low CD4 cell counts is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• Chest x-ray and ultrasound must be performed within 12 (8 or 12) weeks before the study enrollment (I took out the ct scan of abdomen and pelvis)
• Patient must provide study-specific informed consent before study entry.

Exclusion Criteria:

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast or oral cavity.
• Patients cannot have any neuroendocrine histology in pathology.
• Prior systemic chemotherapy for the current cervical cancer, note that prior chemotherapy for a different cancer is allowable.
• Prior radiation therapy to the pelvis that would result in overlap of radiation therapy fields.
• Severe active co-morbidity, defined as follows:
• Unstable angina or congestive heart failure requiring hospitalization within the last six months.
• Transmural myocardial infarction within the previous six months.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of the study entry.
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry.
• Coagulation defects; note, however, that coagulation parameter are not required for entry into this protocol.
• Prior allergic reaction to cisplatin or other platinum drugs.
• Patients with para-aortic nodes or distant metastasis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Treatment; External Beam pelvic radiation therapy daily dose of 1.8-2 Gray (Gy) per session for 25 sessions to accomplish 45 Gy Chemotherapy ( cisplatin 40mg/m2), intravenous administration of chemotherapy once a week in an hour infusion Type II or type III open radical hysterectomy after 4-6 weeks after completion of external beam radiation	Radiation: Standard radiotherapy; External Bean Pelvic Radiation: 50 Gy in 15 fractions, with weekly cisplatin.; Procedure: Radical hysterectomy; Radical hysterectomy and pelvic and paraaortic lymph node resection; Other Names: Surgery
Experimental: hypofractionated treatment; External Beam pelvic radiation therapy daily dose of 1.8-2gy per session for 15 sessions to accomplish 37.5 Gy Chemotherapy ( cisplatin 40mg/m2), intravenous administration of chemotherapy once a week in an hour infusion Type II or type III open radical hysterectomy after 4-6 weeks after completion of external beam radiation	Procedure: Radical hysterectomy; Radical hysterectomy and pelvic and paraaortic lymph node resection; Other Names: Surgery; Radiation: hypofractionated radiotherapy; External Bean Pelvic Radiation: 37.5 Gy in 15 fractions, with weekly cisplatin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute and late toxicity.	Number of Participants With Treatment-Related Adverse Events as Assessed by RTOG	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Number of Participants dead at two years according to kaplan-meyer analysis	2 years
disease specific survival	Number of Participants dead of disease at two years according to kaplan-meyer analysis	2 years
equivalent treatment	hypofractionated radiotherapy is similar in toxicity and disease control compared to standard external beam treatment.	2 years
Surgical complications	comparison of surgical complications between the two arms of treatment according to The Clavien-Dindo classification.	1 year

Collaborators and Investigators

• Sponsor: National Institute of Cancerología
• Investigators: Principal Investigator: David F Cantu-de Leon, MD, Msc, PhD, Instituto Nacional de Cancerologia, Columbia

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2017
• Primary Completion (Estimated): November 10, 2024
• Study Completion (Estimated): November 10, 2025

Study Registration Dates

• First Submitted: November 5, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 12, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms
• Other Study ID Numbers: 017/020/ICI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: 2 years
• IPD Sharing Access Criteria: the data will be shared with scientific and academic institutions or research groups that study the same topic and with the regulatory and ethical authorities that require it, to ensure the quality and accuracy of the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No