Chemotherapy and Pelvic Hypofractionated Radiation Followed by Brachytherapy for Cervical Cancer

NCT04070976 | Unknown

• 1 other identifier: 019/036/ICI
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this trial is to assess the safety and response rate to concomitant chemotherapy and external hypofractionated radiotherapy followed by brachytherapy in patients with clinical stage III cervical cancer. The trial will take place in the National Cancer Institute (INCan). Patients will be randomized into two groups: chemotherapy with external standard fractionated radiotherapy (45 Gy in 25 fractions) followed by brachytherapy or chemotherapy with external hypofractionated radiotherapy (37.5 Gy in 15 fractions) followed by brachytherapy.

Conditions

Cervical Cancer

Keywords

hypofractionated radiotherapy; Brachytherapy

Outcome Measures

Primary Outcomes (1)

• Acute and late toxicity

  Number of Participants With Treatment-Related Adverse Events as Assessed by RTOG

  2 years

Secondary Outcomes (5)

• Treatment efficacy

  2 years

• Disease-free survival rate

  2 years

• Overall survival rate

  2 years

• Satisfaction assessed by EORTC

  2 years

• Direct and indirect costs related to treatment.

  2 years

Study Arms (2)

Standard treatment

ACTIVE COMPARATOR

Cisplatin 40mg/m2 weekly and concomitant pelvic radiotherapy (45 Gray/25 fractions) followed by brachytherapy 28Gray at point A.

Radiation: Standard therapy

Experimental treatment

EXPERIMENTAL

Cisplatin 40mg/m2 weekly and hypofractionated concomitant external radiotherapy (37,50 Gray/15 fractions) followed by brachytherapy 28 Gray at point A.

Radiation: Hypofractionated therapy

Interventions

Hypofractionated therapy RADIATION

All patients will be treated with an external beam of 37.5 Gray in 15 fractions (2.5 Gray / fraction). They will be treated once a day, 5 days a week. If photon energy 6 MV or 10 MV is used, the patient should be treated with a 4-field technique using the anterior/posterior field and 2 lateral fields. The specification of the dose is in terms of a dose to a point at or near the center of the target volume. For all field dispositions, the dose specification point is the common isocenter of all beams.

Experimental treatment

Standard therapy RADIATION

All patients will be treated with external beam radiotherapy with 50 Gray in 25 fractions (1.8-2 Gray / fraction). They will be treated once a day, 5 days a week. If photon energy 6 MV or 10 MV is used, the patient should be treated with a 4-field technique using anterior/posterior fields and 2 lateral fields. The specification of the dose is in terms of a dose to a point at or near the center of the target volume. For all field dispositions, the dose specification point is the common isocenter of all beams.

Standard treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women over 18 years old
• Cervical Cancer at IIIA, IIIB y IIIC1 FIGO´s clinical stages
• Histology: squamous, adenosquamous or adenocarcinoma
• No previous treatment
• No distance metastases, discard by Positron Emission Tomography (PET)/CT
• Functional State ECOG (Eastern Cooperative Oncology Group) 0-2
• Complete Blood count obtained at least 14 days before admission to the study with adequate bone marrow function defined as:
• Absolute neutrophil count ≥ 1,500 cell/mm3
• Platelets ≥ 100,000 cell/mm3
• Hemoglobin ≥ 10.0 g/dl
• Leukocyte count ≥ 4000 cell/mm3
• Adequate Renal Function defined as:
• Serum Creatinine ≤ 1.5 mg/dl within 14 days before admission to the study
• Patients with HIV infection (human immunodeficiency virus) must have a CD4 cell count ≥ 350 cells / mm3 measured within 14 days prior to study entry (no HIV test is required)
• The patient must understand the protocol and provide the specific informed consent of the study before admission

You may not qualify if:

• Patients who had chemotherapeutic, surgical and/or radiotherapy treatment for female reproductive tract pathologies
• Previous invasive neoplasia (except non-melanoma skin cancer) unless there is complete remission of the disease of 3 years minimum (For example, breast cancer or oral cavity cancer)
• Previous systemic chemotherapy for current cervical cancer, take into account that prior chemotherapy for a different cancer is accepted, as long as they have been at least 3 years
• Severe active or non-controlled co-morbidities, defined as:
• Unstable angina and/or congestive heart failure that required hospitalization in the last 6 months.
• Transmural myocardial infarction in the last 6 months.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the beginning of the study.
• Chronic obstructive pulmonary disease exacerbation or another respiratory disease that requires hospitalization or that contraindicates the trial therapy at the time of admission.
• Crohn's disease or ulcerative colitis.
• Prior allergic reaction to cisplatin or other drugs based on platinum.
• Other factors that contraindicate experimental therapy.

Sponsors & Collaborators

• National Institute of Cancerología: lead

Study Sites (1)

David Cantu de Leon

Mexico City, Tlalpan, 14080, Mexico

RECRUITING

Related Publications (20)

• Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.

  PMID: 25220842 BACKGROUND

• Gosvig CF, Huusom LD, Andersen KK, Duun-Henriksen AK, Frederiksen K, Iftner A, Svare E, Iftner T, Kjaer SK. Long-term follow-up of the risk for cervical intraepithelial neoplasia grade 2 or worse in HPV-negative women after conization. Int J Cancer. 2015 Dec 15;137(12):2927-33. doi: 10.1002/ijc.29673. Epub 2015 Jul 25.

  PMID: 26139420 BACKGROUND

• Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.

  PMID: 10202164 BACKGROUND

• Carlson RW, Scavone JL, Koh WJ, McClure JS, Greer BE, Kumar R, McMillian NR, Anderson BO. NCCN Framework for Resource Stratification: A Framework for Providing and Improving Global Quality Oncology Care. J Natl Compr Canc Netw. 2016 Aug;14(8):961-9. doi: 10.6004/jnccn.2016.0103.

  PMID: 27496112 BACKGROUND

• Robin TP, Amini A, Schefter TE, Behbakht K, Fisher CM. Disparities in standard of care treatment and associated survival decrement in patients with locally advanced cervical cancer. Gynecol Oncol. 2016 Nov;143(2):319-325. doi: 10.1016/j.ygyno.2016.09.009. Epub 2016 Sep 16.

  PMID: 27640961 BACKGROUND

• Greenup RA, Blitzblau RC, Houck KL, Sosa JA, Horton J, Peppercorn JM, Taghian AG, Smith BL, Hwang ES. Cost Implications of an Evidence-Based Approach to Radiation Treatment After Lumpectomy for Early-Stage Breast Cancer. J Oncol Pract. 2017 Apr;13(4):e283-e290. doi: 10.1200/JOP.2016.016683. Epub 2017 Mar 14.

  PMID: 28291382 BACKGROUND

• Muckaden MA, Budrukkar AN, Tongaonkar HB, Dinshaw KA. Hypofractionated radiotherapy in carcinoma cervix IIIB: Tata Memorial Hospital experience. Indian J Cancer. 2002 Oct-Dec;39(4):127-34.

  PMID: 12928570 BACKGROUND

• Zhang H, Wang JZ, Mayr N, Kong X, Yuan J, Gupta N, Lo S, Grecula J, Montebello J, Martin D, Yuh W. Fractionated grid therapy in treating cervical cancers: conventional fractionation or hypofractionation? Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):280-8. doi: 10.1016/j.ijrobp.2007.08.024. Epub 2007 Oct 29.

  PMID: 17967516 BACKGROUND

• Hoffman KE, Voong KR, Pugh TJ, Skinner H, Levy LB, Takiar V, Choi S, Du W, Frank SJ, Johnson J, Kanke J, Kudchadker RJ, Lee AK, Mahmood U, McGuire SE, Kuban DA. Risk of late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: results from a randomized trial. Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):1074-84. doi: 10.1016/j.ijrobp.2014.01.015.

  PMID: 24661661 BACKGROUND

• Antoni S, Soerjomataram I, Moller B, Bray F, Ferlay J. An assessment of GLOBOCAN methods for deriving national estimates of cancer incidence. Bull World Health Organ. 2016 Mar 1;94(3):174-84. doi: 10.2471/BLT.15.164384. Epub 2016 Jan 28.

  PMID: 26966328 BACKGROUND

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019 Apr 15;144(8):1941-1953. doi: 10.1002/ijc.31937. Epub 2018 Dec 6.

  PMID: 30350310 BACKGROUND

• Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynaecol Obstet. 2018 Oct;143 Suppl 2:22-36. doi: 10.1002/ijgo.12611.

  PMID: 30306584 BACKGROUND

• FIGO Committee on Gynecologic Oncology. FIGO staging for carcinoma of the vulva, cervix, and corpus uteri. Int J Gynaecol Obstet. 2014 May;125(2):97-8. doi: 10.1016/j.ijgo.2014.02.003. Epub 2014 Feb 22. No abstract available.

  PMID: 24630859 BACKGROUND

• Chuang LT, Temin S, Camacho R, Duenas-Gonzalez A, Feldman S, Gultekin M, Gupta V, Horton S, Jacob G, Kidd EA, Lishimpi K, Nakisige C, Nam JH, Ngan HYS, Small W, Thomas G, Berek JS. Management and Care of Women With Invasive Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Clinical Practice Guideline. J Glob Oncol. 2016 May 25;2(5):311-340. doi: 10.1200/JGO.2016.003954. eCollection 2016 Oct.

  PMID: 28717717 BACKGROUND

• Leath CA 3rd, Monk BJ. Twenty-first century cervical cancer management: A historical perspective of the gynecologic oncology group/NRG oncology over the past twenty years. Gynecol Oncol. 2018 Sep;150(3):391-397. doi: 10.1016/j.ygyno.2018.06.023. Epub 2018 Jun 27.

  PMID: 29954593 BACKGROUND

• Kirwan JM, Symonds P, Green JA, Tierney J, Collingwood M, Williams CJ. A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer. Radiother Oncol. 2003 Sep;68(3):217-26. doi: 10.1016/s0167-8140(03)00197-x.

  PMID: 13129628 BACKGROUND

• Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, Chon HS, Chu C, Clark R, Cohn D, Crispens MA, Damast S, Dorigo O, Eifel PJ, Fisher CM, Frederick P, Gaffney DK, Han E, Huh WK, Lurain JR, Mariani A, Mutch D, Nagel C, Nekhlyudov L, Fader AN, Remmenga SW, Reynolds RK, Tillmanns T, Ueda S, Wyse E, Yashar CM, McMillian NR, Scavone JL. Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019 Jan;17(1):64-84. doi: 10.6004/jnccn.2019.0001.

  PMID: 30659131 BACKGROUND

• Das S, Subhashini J, Rami Reddy JK, KantiPal S, Isiah R, Oommen R. Low-dose fractionated radiation and chemotherapy prior to definitive chemoradiation in locally advanced carcinoma of the uterine cervix: Results of a prospective phase II clinical trial. Gynecol Oncol. 2015 Aug;138(2):292-8. doi: 10.1016/j.ygyno.2015.05.020. Epub 2015 May 23.

  PMID: 26013695 BACKGROUND

• Duenas-Gonzalez A, Zarba JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, Orlando M. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011 May 1;29(13):1678-85. doi: 10.1200/JCO.2009.25.9663. Epub 2011 Mar 28.

  PMID: 21444871 BACKGROUND

Related Links

• Human papillomavirus (HPV) and cervical cancer \[Internet\]

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• David F Cantú-deLeón

  Instituto Nacional de Cancerologia de Mexico

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David F Cantú-de León, Md, MSc. PhD

CONTACT

+525537093156; dfcantu@gmail.com

Lenny N Gallardo-Alvarado, MD, MSc

CONTACT

+52553702118; dra.ngallardo@yahoo.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of clinical trials department

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: August 28, 2019
• Study Start: July 1, 2019
• Primary Completion: July 30, 2024
• Study Completion: December 30, 2024
• Last Updated: November 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 2 years
• 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.

Locations

ME (1)