A Phase III Randomised Clinical Trial of Ultrasound Groin Monitoring Versus Groin Lymph Node Dissection to De-Escalate the Extent of Surgery in Vulvar Cancer

NCT ID: NCT06476639

Last Updated: 2025-11-28

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

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

640 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2035-12-31

Brief Summary

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This study is a phase III, open label, multicentre, three-group, randomised clinical trial. The primary aim of this study is to determine whether intensive groin ultrasound monitoring (1) is effective and safe to replace invasive groin lymph node dissection (LND) to manage vulvar cancer, (2) decreases the morbidity associated with vulvar cancer surgery, and (3) is cost effective.

Detailed Description

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Treatment of vulvar cancer causes significant morbidity. Despite being a rare cancer, at least 2500 survivors of vulvar cancer live in Australia. Most survivors live with the detrimental, life-long impacts resulting from their cancer treatment because there are currently no alternatives to mitigate these impacts. The personal and societal burden this entails is significant. To control such cancer-associated burden is a national priority.

Clinical palpation of the groin region and computed tomography (CT) scans do not reliably detect groin node involvement. Hence, current clinical guidelines recommend all women diagnosed at apparent Stage I or II have a surgical groin LND. This can be performed as a full IFL (full LND) to remove all groin nodes, or as a sentinel node biopsy (SNB) to remove selected (one or two) nodes. SNB is less invasive, however, is appropriate only for vulvar cancers \<4cm in diameter and unifocal tumours (\~50% of all Stage I and II vulvar cancers). SNB is also associated with a false negative rate (10%) that increases the risk of undetected nodes.

In 25% of cases (\~80 Australian women per year), groin LND will reveal positive nodes (i.e., metastases), which triggers a referral for radiation treatment. If positive groin nodes are missed, and over time become enlarged, clinically palpable and attached to the overlying skin, \>90% of women will die within 12 months, despite subsequent treatment. Conversely, if groin node involvement is detected early (e.g., by ultrasound) while still small, survival outcomes are excellent. Ultrasound technology is potentially as accurate as LND due to recent advances in resolution and technologies such as 2D/3D volumetric assessments and tissue flow. Furthermore, ultrasound is superior to medical resonance imaging (MRI), and to standard CT and positron emission tomography (PET) scans in capturing groin node involvement because it has a higher resolution, avoids harmful radiation and the technology is readily accessible outside of high-volume metropolitan areas.

The investigators propose to reduce surgical morbidity by replacing upfront groin LND for vulvar cancer patients with serial high-resolution ultrasound to detect groin metastases. Groin LND will only be necessary for the few women with ultrasound-detected metastases when they are still small. The ANVU trial will determine the value of serial groin ultrasound examinations in stage 1b and 2 vulvar cancer patients and whether it is feasible and safe to de-escalate the extent of vulvar cancer surgery to achieve improved outcomes for affected patients.

Women with this rare cancer bear an unacceptably high (and potentially avoidable) treatment-related burden. This clinical trial is the first step to address this problem in a novel yet pragmatic way. The potential overall outcome of ANVU could be a novel, less invasive alternative to vulvar cancer LND hypothesised to be associated with significantly less morbidity, without compromising survival.

Conditions

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Vulvar Cancer Stage I Vulvar Cancer Stage II Lymph Node Metastasis Groin Node Ultrasound Therapy; Complications

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A phase III, open label, multicentre, three-group, randomised clinical trial.

640 eligible females aged 18 or older with clinically stage 1b or 2 vulvar cancer will receive a bilateral groin node ultrasound up to 30 days prior to planned surgery:

Participants with normal/negative baseline groin ultrasounds will be randomly assigned to two groups (3:1 randomisation). The Intervention Group will receive serial bilateral groin node ultrasounds and clinical examinations for 18 months (groin lymph nodes are not removed). The Standard Group will undergo upfront full groin lymph node dissection (LND) or sentinel node biopsy (SNB) based on clinician choice (according to local clinical practice management guidelines).

Participants with abnormal baseline groin ultrasound (third group) will receive an upfront full groin LND or SNB, consistent with the current standard treatment, according to local clinical practice management guidelines.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Participants with normal/negative baseline groin ultrasounds - Intervention Group

Surgical removal of primary tumour and serial high-resolution bilateral groin ultrasound monitoring every 2 months for 12 months, and at month 15 and month 18, with clinical examination at 8 weeks, 4 months, 8 months, 12 months, 15 months, and 18 months (n=360).

Group Type EXPERIMENTAL

High-resolution bilateral groin ultrasound monitoring

Intervention Type DIAGNOSTIC_TEST

Participants in the Interventional Group will undergo surgical excision of the primary tumour, either via radical local excision or radical vulvectomy. Post-vulvar surgery, participants will receive a groin node ultrasound every 2 months for 12 months, and at month 15 and month 18, and a clinical examination at 8 weeks, 4 months, 8 months, 12 months, 15 months, and 18 months. Senior imaging specialists review bilateral ultrasound scans for positive lymph nodes or suspicious findings, promptly sending reports to the primary care physician and trial manager within 5 business days. If positive nodes are detected, participants will consult their primary care physician for options. Depending on clinical judgment, they may be referred for LND or continue with serial ultrasounds and clinical exams based on preference and clinician guidance.

Participants with normal/negative baseline groin ultrasounds - Standard Group

Surgical removal of primary tumour and upfront full groin lymph node dissection (LND) or sentinel node biopsy (SNB) based on clinician choice (according to local clinical practice management guidelines) (n=120).

Group Type NO_INTERVENTION

No interventions assigned to this group

Participants with suspicious/indeterminate baseline groin ultrasound - Standard Treatment

Participants with suspicious/indeterminate baseline groin ultrasound (third group) will receive an upfront full groin LND or SNB, consistent with the current standard treatment, according to local clinical practice management guidelines (n=160).

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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High-resolution bilateral groin ultrasound monitoring

Participants in the Interventional Group will undergo surgical excision of the primary tumour, either via radical local excision or radical vulvectomy. Post-vulvar surgery, participants will receive a groin node ultrasound every 2 months for 12 months, and at month 15 and month 18, and a clinical examination at 8 weeks, 4 months, 8 months, 12 months, 15 months, and 18 months. Senior imaging specialists review bilateral ultrasound scans for positive lymph nodes or suspicious findings, promptly sending reports to the primary care physician and trial manager within 5 business days. If positive nodes are detected, participants will consult their primary care physician for options. Depending on clinical judgment, they may be referred for LND or continue with serial ultrasounds and clinical exams based on preference and clinician guidance.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Females, over 18 years, with histologically confirmed SCC or adenocarcinoma of the vulva
* Clinically stage 1b or 2 on medical imaging (CT or MRI scan of pelvis, abdomen, and chest), without evidence of regional or distant metastatic disease
* Willing and able to undergo IFL/SNB according to local clinical practice management guidelines
* Willing and able to comply with all study requirements, timing and/or nature of required assessments.
* Signed written informed consent
* Negative (serum or urine) pregnancy (BHCG) test ≤ 30 days of surgery ONLY in pre-menopausal women and women \< 2 years after the onset of menopause.

Exclusion Criteria

* Women with non-invasive vulvar conditions (e.g. non-invasive non-mammary Paget's disease)
* Clinical or medical imaging evidence of regional and/or distant metastatic disease
* Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
* Other prior malignancies \<5 years before inclusion, except for successfully treated keratinocyte skin cancers, or ductal carcinoma in situ
* Estimated life expectancy of ≤6 months
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Royal Brisbane and Women's Hospital

OTHER_GOV

Sponsor Role collaborator

Queensland Centre for Gynaecological Cancer

OTHER_GOV

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Andreas Obermair, MD

Role: STUDY_CHAIR

Director, Queensland Centre for Gynaecological Cancer Research

Locations

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John Hunter Hospital

Newcastle, New South Wales, Australia

Site Status

The Royal Darwin Hospital

Darwin, Northern Territory, Australia

Site Status

The Wesley Hospital

Auchenflower, Queensland, Australia

Site Status

St Andrew's War Memorial Hospital

Brisbane, Queensland, Australia

Site Status

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Site Status

Buderim Private Hospital

Buderim, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Mercy Hospital for Women

Heidelberg, Victoria, Australia

Site Status

Royal Women's Hospital

Parkville, Victoria, Australia

Site Status

Countries

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Australia

Central Contacts

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Brianna Armstrong

Role: CONTACT

07 3346 5063

Sara Baniahmadi

Role: CONTACT

07 3346 5073

Facility Contacts

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Anne Mellon

Role: primary

Michelle Harris, MD

Role: primary

Brianna Armstrong

Role: primary

+61 7 3346 5063

Sara Baniahmadi

Role: backup

+61 7 3346 5073

Brianna Armstrong

Role: primary

07 3346 5063

Sara Baniahmadi

Role: backup

0733465073

Brianna Armstrong

Role: primary

07 3346 5063

Sara Baniahmadi

Role: backup

07 3346 5073

Brianna Armstrong

Role: primary

0733465063

Sara Baniahmadi

Role: backup

0733465073

Martin Oehler

Role: primary

+61 8 8222 4816

Adam Pendlebury, MD

Role: primary

Estefania Vicario

Role: primary

Niveditha Rajadevan, MD

Role: backup

Other Identifiers

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ANVU

Identifier Type: -

Identifier Source: org_study_id

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