This study will determine whether there is a difference in disease free survival for patients treated with either a 1cm excision margin or 2cm margin for clinical stage II (pT2b-pT4b) primary cutaneous melanoma (AJCC 8th edition, Table 1). The study…
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Disease-Free Survival: Time from randomisation until the first clinically,
histologically or radiologically confirmed recurrence of melanoma at any body
site, or death from any cause.
Secondary outcome
1. Local recurrence: time from randomisation to any clinically, histologically
or radiologically confirmed local recurrence of melanoma including satellite
lesions and in transit metastases between the primary site and the regional
draining lymph nodes
2. Distant Disease-free survival: time from randomisation to any clinically,
histologically or radiologically confirmed distant recurrence of melanoma
3. Melanoma specific survival: Time from randomisation to death due to melanoma
4. Overall Survival: time from randomisation to death from any cause.
5. QoL and neuropathic pain assessments at baseline, 3, 6, 12 and 24 and at
melanoma recurrence.
6. Surgery related adverse events up to 30 days from the date of surgery.
7. Adverse events within 1 year
8. Health economic evaluation resource utilisation and cost-utility analysis
Background summary
A wide, radical excision to remove the entire primary tumour, to prevent spread
and local recurrence is a classic surgical teaching. In primary melanoma, a
secondary wider excision around the original biopsy scar is advocated to reduce
risk of local recurrence and improve patient outcomes. Surprisingly, the detail
of the wide excision is still highly controversial. Surgical margins vary
significantly worldwide, from 1cm to 3cm, translating into large excision
defects from 2cm to 6cm across. The management of patients with intermediate
and high-risk primaries is particularly speculative. There is a growing concern
internationally amongst surgeons that the excess morbidity caused by the larger
excision defects, including increased hospital stay, complications and need for
reconstructive surgery, coupled with prolonged rehabilitation and increased
risk of chronic pain is not justifiable. Many surgeons suspect that 1cm is
ample. An appropriately designed trial of adequate size is clearly needed to
unify international guidance and to benefit the large and increasing numbers of
melanoma patients worldwide.
Study objective
This study will determine whether there is a difference in disease free
survival for patients treated with either a 1cm excision margin or 2cm margin
for clinical stage II (pT2b-pT4b) primary cutaneous melanoma (AJCC 8th edition,
Table 1). The study is designed to be able to prove or disprove that there is
no difference in risk of melanoma recurrence between the two groups of
patients. This study is designed to show that the risk of long-term pain
associated with surgery can be reduced. If the study achieves its primary
objective and demonstrates safety with a narrower margin, then we will also be
able to determine how much of an impact the narrower excision has on patients
in terms of improved quality of life and reduced side effects from the surgery
and melanoma disease. This trial will also evaluate and determine the economic
impact of narrower excision margins on the health services and society in
general.
Study design
This is a randomised, controlled, multi-centre, non-inferiority,
internationally recruiting, phase III clinical trial.
Intervention
Once determined as being eligible, patients will be randomised 1:1 to either a
1 cm excision margin or a 2 cm excision margin, in combination with a staging
sentinel lymph node biopsy.
Study burden and risks
Time associated with filling out questionnaires
St Kilda Road 553
Melbourne VIC 3004
AU
St Kilda Road 553
Melbourne VIC 3004
AU
Listed location countries
Age
Inclusion criteria
1. Patients must have a stage II primary invasive cutaneous melanoma with
Breslow thickness 2.01mm to 4mm or >4mm with or without ulceration (pT3a-pT4b,
AJCC 8th edition) as determined by
diagnostic biopsy (narrow excision, incision or punch biopsy) and
subsequent histopathological analysis.
2. Must have a primary melanoma that is cutaneous (including head, neck, trunk,
extremity, scalp, palm or sole).
3. An uninterrupted 2cm margin must be technically feasible around biopsy scar
or primary melanoma.
4. Surgical intervention (which refers to SLNB and WLE as these are both to be
done on the same day), must be completed within 120 days of the original
diagnosis.
5. Patients must be 18 years or older at time of consent.
6. Patient must be able to give informed consent and comply with the treatment
protocol and follow-up plan.
7. Life expectancy of at least 5 years from the time of diagnosis, not
considering the melanoma in question, as determined by the PI.
8. Patients must have an ECOG performance score between 0 and 1 at screening.
9. A survivor of prior cancer is eligible provided that ALL of the following
criteria are met and documented:
o The patient has undergone potentially curative therapy for all prior
malignancies,
o There has been no evidence of recurrence of any prior malignancies
for at least FIVE years (with the exception if successfully treated
uterine/cervical or non-melanoma skin cancers
(SCCs/BCCs with no evidence of recurrence), and
o The patient is deemed by their treating physician to be at low risk
of recurrence from previous malignancies.
Exclusion criteria
1. Uncertain diagnosis of melanoma i.e. so-called *melanocytic lesion of
unknown malignant potential*.
2. Patient has already undergone wide local excision at the site of the primary
index lesion.
3. Patient unable or ineligible to undergo staging sentinel lymph node biopsy
of the primary index lesion.
4. Desmoplastic or neurotropic melanoma: with any patient where pathology
determines melanoma as PURE desmoplastic (as per WHO definition of >90%
desmoplasia),
they are not eligible for this study. However other melanomas with less
than 90% desmoplasia or mixed subtypes are eligible unless there is
neurotropism present (peri
neural invasion). Neurotropism in any type of melanoma is an exclusion.
Peri-neural invasion does not include entrapment of nerves within the main
primary tumour
mass*.
5. Microsatellitosis as per AJCC 8th edition definition
6. Subungual melanoma
7. Patient has already undergone a local flap reconstruction of the defect
after excision
of the primary and determination of an accurate excision margin is
impossible.
8. History of previous or concurrent (i.e., second primary) invasive melanoma.
9. Melanoma located distal to the metacarpophalangeal joint; on the tip of the
nose; the eyelids or on the ear; genitalia, perineum or anus; mucous membranes
or internal
viscera.
10. Physical, clinical, radiographic or pathologic evidence of satellite,
in-transit, regional, or distant metastatic melanoma.
11. Patient has undergone surgery on a separate occasion to clear the lymph
nodes of the probable draining lymphatic field, including sentinel lymph node
biopsy, of the
index melanoma.
12. Any additional solid tumour or hematologic malignancy during the past 5
years (with exception of non-melanoma skin cancers (T1 skin lesions of squamous
cell
carcinoma (SCCs), basal cell carcinoma (BCC*s)), or uterine/cervical
cancer).
13. Melanoma-related operative procedures not corresponding to criteria
described in the protocol.
14. Planned adjuvant radiotherapy to the primary melanoma site after Wide Local
Excision is not permitted as part of the protocol and any patients given this
treatment would
be excluded from the study.
15. History of organ transplantation.
16. Oral or parenteral immunosuppressive agents (not topical or inhaled
steroids) at enrolment or within 6 months prior to enrolment.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03860883 |
| CCMO | NL75543.096.21 |