HYpofractionated Pelvic Radiotherapy for Advanced Cervical Cancers INeligible for ChemoTherapy

NCT05210270 | Not Yet Recruiting Phase 1

• 2 other identifiers: USTH-BCI-RO-2022-01REC-2021-08-104-CT
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

BACKGROUND: For patients with locally advanced cervical cancer (LACC) ineligible for concurrent chemotherapy, radiotherapy (RT) alone achieves complete response rate (CRR) \<70% and long-term locoregional control (LRC) \<62%. Hypofractionated (HF-)RT using older techniques results in comparable CRR and disease control, and low late toxicity rates (4-8%). Dose-adapted HF-RT using intensity-modulated radiotherapy (IMRT) with nodal simultaneous integrated boost (nSIB) could improve tumor control and toxicity. GENERAL OBJECTIVE: To determine the effectiveness and safety of HF-RT with (or without) nSIB in LACC among patients who are chemo-ineligible. PRIMARY OBJECTIVES: Phase 1: To determine the maximum tolerated dose (MTD) for nSIB used in combination with pelvic HF-RT (2.67 Gray (Gy) x 15 fractions), using IMRT Phase 2: To assess the efficacy of HF-RT ± nSIB in terms of complete response rates at 3 months SECONDARY OBJECTIVES: To assess the efficacy of HF-RT ± nSIB in terms of progression free survival (PFS), locoregional PFS, distant metastasis free survival (DMFS), cervical cancer specific survival (CCSS), overall survival (OS) To assess the acute and late toxicity of HF-RT ± nSIB, and patient-reported quality of life outcomes EXPLORATORY OBJECTIVES: To evaluate the predictive utility of clinical and dosimetric variables for tumor response/control and toxicity. Variables: age, performance status, T- and N-stage, T-score, histology, baseline hemoglobin, clinical target volume and organs-at-risk doses, overall treatment time STUDY DESIGN: Phase 1: Dose-escalation study (standard 3+3 design) Phase 2: Single-arm clinical trial (Simon's two-stage design) STUDY TREATMENTS: Pelvic HF-RT ± nSIB to 40 Gy in 15 fractions using IMRT, followed by brachytherapy (BRT) 6.5-7.5 Gy x 4 fractions using 2D or image-guided techniques SAMPLE SIZE: One-sided hypothesis testing. H0: CRR p0 ≤64%; H1: CRR p1 ≥84%. Simon 2 stage: First stage, n1=28 will be enrolled. If response (r1) ≤18, the study will be stopped for futility. Otherwise, second stage: n2=22, for a total of 50. H0 will be rejected if r1+r2 ≥38, in 50 patients. This yields a type I error rate of 5% and power of 95% when the true response rate is ≥84%. Accrual: Accounting for 10% attrition, a n=55 will be targeted. At a rate of 4-5 patients quarterly, accrual may take 33-42 months. The trial may be opened to other centers to accelerate accrual.

Conditions

Locally Advanced Cervical Carcinoma

Keywords

Hypofractionation; Nodal simultaneous integrated boost; Intensity-modulated radiotherapy

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (for phase 1)

  The highest dose studied for which the incidence of dose-limiting toxicity was less than 33%

  4 months

• Complete response rate (for phase 2)

  Proportion of treated patients with disappearance of all lesions on clinical and radiologic examination

  3 months

Secondary Outcomes (12)

• Progression-free survival

  5 years

• Locoregional progression-free survival

  5 years

• Metastasis-free survival

  5 years

• Cervical cancer-specific survival

  5 years

• Overall survival

  5 years

Interventions

Hypofractionation RADIATION

Phase 1 (Dose Escalation Study): Pelvic hypofractionated radiotherapy (40 Gy over 15 daily fractions) with nSIB 45 Gy (first dose level) and 48 Gy (second dose level); to be followed by brachytherapy (6.5-7.5 Gy x 4 fractions) Phase 2 (Efficacy Study): Pelvic hypofractionated radiotherapy (40 Gy over 15 daily fractions) with (or without) nSIB 45-48 Gy (depending on phase 1 results); to be followed by brachytherapy (6.5-7.5 Gy x 4 fractions)

Also known as: Nodal simultaneous integrated boost, Brachytherapy

Eligibility Criteria

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

You may qualify if:

• Females aged ≥18 years
• Histologically confirmed cervical squamous, adeno-, or adenosquamous carcinoma
• Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) Stage IIIA-IIIC1, IVA
• Pelvic nodal metastases (for the phase 1 cohorts)
• Contraindication to chemotherapy
• Brachytherapy candidate
• World Health Organization (WHO)/ECOG performance status of ≤2
• Life expectancy of at least 12 weeks
• Adequate bone marrow function: Absolute neutrophil count ≥1,500 cell/mm3; Platelets ≥100,000 cell/mm3; Hemoglobin ≥10.0 g/dL; Leukocyte count ≥4,000 cell/mm3

You may not qualify if:

• Other histology (small cell, neuroendocrine, lymphoma, sarcoma, etc.)
• FIGO Stage IIIC2 (para-aortic nodal metastases)
• Clinical and/or radiologic evidence of metastatic disease
• History of another malignancy except for the following: malignancy treated with curative intent and with no known active disease ≥5 years and of low potential risk for recurrence; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma-in-situ without evidence of disease
• Pregnancy
• Uncontrolled concurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic GI conditions associated with diarrhea (including Crohn's disease or ulcerative colitis), or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events or compromise the ability of the patient to give written informed consent
• Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse
• Prior hysterectomy
• Prior treatment for cervical cancer
• Prior pelvic radiotherapy
• Concomitant anti-cancer therapy

Sponsors & Collaborators

• University of Santo Tomas Hospital, Philippines: lead
• Philippine Council for Health Research & Development: collaborator

Related Publications (1)

• Bacorro W, Baldivia K, Dumago M, Bojador M, Milo A, Trinidad CM, Mariano J, Gonzalez G, Sy Ortin T. Phase 1/2 trial evaluating the effectiveness and safety of dose-adapted Hypofractionated pelvic radiotherapy for Advanced Cervical cancers INeligible for ChemoTherapy (HYACINCT). Acta Oncol. 2022 Jun;61(6):688-697. doi: 10.1080/0284186X.2022.2048070. Epub 2022 Mar 14.

  PMID: 35285405 BACKGROUND

MeSH Terms

Interventions

Radiation Dose Hypofractionation; Brachytherapy

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• Warren Bacorro, MD

  University of Santo Tomas Hospital, Philippines

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Warren Bacorro, MD

CONTACT

+639171665927; wrbacorro@ust.edu.ph

Teresa Sy Ortin, MD

CONTACT

ttsy-ortin@ust.edu.ph

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Model Details: Two-phase study Phase 1: Dose-escalation study using standard 3+3 design Phase 2: Single-arm clinical trial using Simon's two-stage design

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 27, 2022
• Study Start: January 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2030
• Last Updated: January 31, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Six months after publication
• Access Criteria: When a request has been approved the study team will provide access to the de-identified individual patient-level data. Signed Data Sharing Agreement must be in place before accessing requested information. Additionally, all users will need to accept specified terms and conditions to gain access.