Ignite Creation Date:
2024-05-06 @ 7:24 AM
Last Modification Date:
2024-10-26 @ 11:48 AM
Study NCT ID:
NCT02526719
Status:
WITHDRAWN
Last Update Posted:
2015-11-01
First Post:
2015-08-14
Brief Title:
Nipple Delay Prior to Nipple Sparing Mastectomy A Pilot RCT
Sponsor:
University Health Network Toronto
Organization:
University Health Network Toronto
Study Overview
Official Title:
Nipple Delay Prior to Nipple Sparing Mastectomy A Pilot RCT
Status:
WITHDRAWN
Status Verified Date:
2015-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study design changed no longer a randomized trial design
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of nipple-sparing mastectomy NSM with immediate breast reconstruction is to reconstruct a breast mound with preservation a patients natural skin envelope Preservation of the nipple and areola complex during mastectomy and breast reconstruction is associated with improved quality of life and a better cosmetic result However this surgical technique relies on tenuous blood supply to maintain the nipple and areola Therefore a certain proportion of women will actually lose their preserved nipple-areolar complex due to vascular insufficiency Furthermore some women may find out after a nipple-sparing mastectomy that cancer had invaded the nipple-areolar complex and would require another operation to completely remove the cancer Despite these devastating complications there have been no controlled studies to investigate mechanisms to reduce the chance of their occurrence
Our research study will use a pre-operative minor procedure to enhance blood flow to the nipple-areola complex prior to standard nipple sparing mastectomy among eligible women undergoing mastectomy for breast cancer or risk reduction A secondary objective is to test how many women actually have active cancer in their nipple at the time of this minor surgical procedure prior to standard NSM The investigators hypothesize that our innovative and novel nipple-delay procedure will reduce the risk of loss of the nipple due to vascular insufficiency and may be of benefit to identify the small proportion of women with nipple-areola complex involvement in order to optimize the ultimate cancer ablation
For this study the investigators propose to undertake a Pilot RCT as the first step in the evaluation of a delay procedure prior to NSM and the results will be used to determine the feasibility and inform the optimal design for a definitive RCT This study question has the potential to set a new standard of care in the management of women seeking NSM for the management of their breast cancer
Our research study will use a pre-operative minor procedure to enhance blood flow to the nipple-areola complex prior to standard nipple sparing mastectomy among eligible women undergoing mastectomy for breast cancer or risk reduction A secondary objective is to test how many women actually have active cancer in their nipple at the time of this minor surgical procedure prior to standard NSM The investigators hypothesize that our innovative and novel nipple-delay procedure will reduce the risk of loss of the nipple due to vascular insufficiency and may be of benefit to identify the small proportion of women with nipple-areola complex involvement in order to optimize the ultimate cancer ablation
For this study the investigators propose to undertake a Pilot RCT as the first step in the evaluation of a delay procedure prior to NSM and the results will be used to determine the feasibility and inform the optimal design for a definitive RCT This study question has the potential to set a new standard of care in the management of women seeking NSM for the management of their breast cancer
Detailed Description:
The surgical management of breast cancer has evolved over the last few decades with cancer extirpation becoming less aggressive in parallel with advances in breast reconstruction Preservation of the nipple-areolar complex NAC at time of mastectomy nipple-sparing mastectomy NSM represents a natural progression within reconstructive and surgical oncology to preserve maximum native skin as is oncologically feasible NSM is associated with improved satisfaction body image and psychological adjustment NSM has received increased attention in the lay media because the ability to preserve the entire breast envelope appeals to patients facing the decision to undergo mastectomy
Clinician attention regarding NSM has focused on the oncologic implications of the residual breast tissue Several systematic reviews of prospective and retrospective studies level II to IV have concluded that NSM does not impair overall or breast cancer specific survival outcomes compared to skin-sparing mastectomy This has fostered the adoption of NSM within North America and Europe The rate of occult NAC involvement ranges from 6 - 30
However the intended purpose of NSM to preserve the NAC may be circumvented if a tenuous sub-dermal blood supply compromises NAC viability Rates of NAC necrosis are variable from 0 to nearly 50 of cases 56 Few studies explored strategies to prevent this potentially devastating complication Recent case series employ the use of the surgical delay phenomenon to improve vascular supply and reduce NAC necrosis during NSM 910 however this strategy has not been directly compared with standard NSM
There have been no controlled studies to investigate mechanisms to reduce the chance of potentially devestating complication of NAC necrosis or minimize the clinical impact of occult tumor involvement in the NAC Because our study is a pilot feasibility study we have 3 specific rationale to support our design using a pilot study first
1 Given lack of evidence to support impaired cancer outcomes there has been greater interest in NSM within our breast cancer community Prior to initiating a full trial it is paramount to determine the extent to which the intervention can be provided as intended
2 There are a number of well-described challenges to undertaking a RCT of a surgical intervention and the extent to which women consent to participate maintain randomized treatment allocation and adhere to study protocol will inform whether this study is feasible at a larger scale It has not been determined whether candidates for NSM would accept an additional surgical procedure to reduce the risk of NAC necrosis Lastly there is the opportunity to identify and revise organization and protocols prior to execution within a full trial
3 Given there is wide variation in reported rates of NAC necrosis it is important to determine the incidence of NAC necrosis within our institutions and use this information to generate and inform sample size calculation The direction of benefit and preliminary estimates of the effect of the intervention will clarify the choice of primary and secondary outcomes and feasibility for a larger scale study
The overarching hypothesis driving the main trial is that patients who are allocated to nipple-delay will have a lower rate of NAC necrosis Additionally we hypothesize may be of benefit to identify the small proportion of women with nipple-areola complex involvement in order to optimize the ultimate cancer ablation
Aim 1 To assess treatment fidelity and acceptability to surgeons of the intervention Hypothesis This pilot RCT will be acceptable to surgeons and surgeons will adhere to the treatment group surgical procedure to which their patient is randomly allocated Aim 2 To determine feasibility and acceptability to patients of randomization treatment uptake and retention and data-collection Hypothesis This pilot RCT will be feasible to implement and acceptable to patients and the results will inform planning of the main study Aim 3 To estimate the proportion of patients in the treatment and control groups that develop NAC necrosis primary outcome and a preliminary estimate of the effect of the intervention on NAC necrosis primary outcome occult cancer and intra-operative NAC perfusion secondary outcomes Hypothesis This pilot study will provide important information regarding treatment effect estimate and variability standard deviation that will be used to guide the design and sample size calculation for the main trial The overarching hypothesis driving the main trial is that patients who are allocated to nipple-delay will have a lower rate of NAC necrosis
Pilot outcomes Treatment fidelity and acceptability to surgeons We will record the proportion of participants who received their randomly allocated treatment assignment to monitor participant adherence to treatment allocation We will record reasons why any deviation from study protocol occurred patient or surgeon-driven and other organizational barriers to meeting usual care ex 21 days between nipple-delay and NSM for experimental-group patients Feasibility and acceptability of randomization treatment allocation and data-collection procedures Patient recruitment and attrition rates will be recorded We will measure the proportion of participants that generate complete primary and secondary outcome measurements and baseline questionnaires
Trial outcomes
Primary outcome We will compare the proportion of patients in each group that develop NAC necrosis defined as necrosis requiring local wound care with dressings or surgical debridement The proportion of patients in each group that develop total 75 of NAC and partial 25 to 75 of NAC NAC necrosis will be measured at 2 week and 4 weeks after the definitive NSM procedure by the treating plastic surgeon and surgical oncologist respectively We will take photographs to provide objective documentation
Secondary outcomes
1 The proportion of women in each group who require secondary NAC excision due to positive pathology review after NSM after the retro-areolar and nipple core biopsy during surgical delay intervention group or definitive NSM control group
2 To include an objective and immediate measure of NAC perfusion we will compare the mean perfusion score of the NAC between groups using indocyanine green infusion and the SPY Imaging System Lifecell Corp immediately after tissue expander or implant placement and skin closure during the NSM We will use this as an objective measure of perfusion but will not influence clinical decision making with regards to NAC viability
For the pilot this study is significant to generate high-quality evidence-based data and to determine the feasibility to undertake and complete a full-scale RCT The overarching study has the potential to influence clinical practice and is very contemporary in the management of patients undergoing mastectomy for breast cancer or risk reduction If nipple-delay is effective in reducing the rate of NAC necrosis then our proposed intervention has the potential to change clinical practice for surgeons who treat women with breast cancer or at high risk for development Furthermore the identification of occult malignancy within the NAC prior to planned NSM may contribute to improved cancer outcomes by not sparing the NAC at the time of mastectomy We hypothesize a positive outcome would engender support within the breast cancer community to uptake an additional stage Therefore our proposed study can be used as a model to incorporate level I evidence into the plastic surgery research community as well as provide robust data to support a change in clinical practice to improve patient outcomes among women undergoing NSM for breast cancer risk-reduction
Clinician attention regarding NSM has focused on the oncologic implications of the residual breast tissue Several systematic reviews of prospective and retrospective studies level II to IV have concluded that NSM does not impair overall or breast cancer specific survival outcomes compared to skin-sparing mastectomy This has fostered the adoption of NSM within North America and Europe The rate of occult NAC involvement ranges from 6 - 30
However the intended purpose of NSM to preserve the NAC may be circumvented if a tenuous sub-dermal blood supply compromises NAC viability Rates of NAC necrosis are variable from 0 to nearly 50 of cases 56 Few studies explored strategies to prevent this potentially devastating complication Recent case series employ the use of the surgical delay phenomenon to improve vascular supply and reduce NAC necrosis during NSM 910 however this strategy has not been directly compared with standard NSM
There have been no controlled studies to investigate mechanisms to reduce the chance of potentially devestating complication of NAC necrosis or minimize the clinical impact of occult tumor involvement in the NAC Because our study is a pilot feasibility study we have 3 specific rationale to support our design using a pilot study first
1 Given lack of evidence to support impaired cancer outcomes there has been greater interest in NSM within our breast cancer community Prior to initiating a full trial it is paramount to determine the extent to which the intervention can be provided as intended
2 There are a number of well-described challenges to undertaking a RCT of a surgical intervention and the extent to which women consent to participate maintain randomized treatment allocation and adhere to study protocol will inform whether this study is feasible at a larger scale It has not been determined whether candidates for NSM would accept an additional surgical procedure to reduce the risk of NAC necrosis Lastly there is the opportunity to identify and revise organization and protocols prior to execution within a full trial
3 Given there is wide variation in reported rates of NAC necrosis it is important to determine the incidence of NAC necrosis within our institutions and use this information to generate and inform sample size calculation The direction of benefit and preliminary estimates of the effect of the intervention will clarify the choice of primary and secondary outcomes and feasibility for a larger scale study
The overarching hypothesis driving the main trial is that patients who are allocated to nipple-delay will have a lower rate of NAC necrosis Additionally we hypothesize may be of benefit to identify the small proportion of women with nipple-areola complex involvement in order to optimize the ultimate cancer ablation
Aim 1 To assess treatment fidelity and acceptability to surgeons of the intervention Hypothesis This pilot RCT will be acceptable to surgeons and surgeons will adhere to the treatment group surgical procedure to which their patient is randomly allocated Aim 2 To determine feasibility and acceptability to patients of randomization treatment uptake and retention and data-collection Hypothesis This pilot RCT will be feasible to implement and acceptable to patients and the results will inform planning of the main study Aim 3 To estimate the proportion of patients in the treatment and control groups that develop NAC necrosis primary outcome and a preliminary estimate of the effect of the intervention on NAC necrosis primary outcome occult cancer and intra-operative NAC perfusion secondary outcomes Hypothesis This pilot study will provide important information regarding treatment effect estimate and variability standard deviation that will be used to guide the design and sample size calculation for the main trial The overarching hypothesis driving the main trial is that patients who are allocated to nipple-delay will have a lower rate of NAC necrosis
Pilot outcomes Treatment fidelity and acceptability to surgeons We will record the proportion of participants who received their randomly allocated treatment assignment to monitor participant adherence to treatment allocation We will record reasons why any deviation from study protocol occurred patient or surgeon-driven and other organizational barriers to meeting usual care ex 21 days between nipple-delay and NSM for experimental-group patients Feasibility and acceptability of randomization treatment allocation and data-collection procedures Patient recruitment and attrition rates will be recorded We will measure the proportion of participants that generate complete primary and secondary outcome measurements and baseline questionnaires
Trial outcomes
Primary outcome We will compare the proportion of patients in each group that develop NAC necrosis defined as necrosis requiring local wound care with dressings or surgical debridement The proportion of patients in each group that develop total 75 of NAC and partial 25 to 75 of NAC NAC necrosis will be measured at 2 week and 4 weeks after the definitive NSM procedure by the treating plastic surgeon and surgical oncologist respectively We will take photographs to provide objective documentation
Secondary outcomes
1 The proportion of women in each group who require secondary NAC excision due to positive pathology review after NSM after the retro-areolar and nipple core biopsy during surgical delay intervention group or definitive NSM control group
2 To include an objective and immediate measure of NAC perfusion we will compare the mean perfusion score of the NAC between groups using indocyanine green infusion and the SPY Imaging System Lifecell Corp immediately after tissue expander or implant placement and skin closure during the NSM We will use this as an objective measure of perfusion but will not influence clinical decision making with regards to NAC viability
For the pilot this study is significant to generate high-quality evidence-based data and to determine the feasibility to undertake and complete a full-scale RCT The overarching study has the potential to influence clinical practice and is very contemporary in the management of patients undergoing mastectomy for breast cancer or risk reduction If nipple-delay is effective in reducing the rate of NAC necrosis then our proposed intervention has the potential to change clinical practice for surgeons who treat women with breast cancer or at high risk for development Furthermore the identification of occult malignancy within the NAC prior to planned NSM may contribute to improved cancer outcomes by not sparing the NAC at the time of mastectomy We hypothesize a positive outcome would engender support within the breast cancer community to uptake an additional stage Therefore our proposed study can be used as a model to incorporate level I evidence into the plastic surgery research community as well as provide robust data to support a change in clinical practice to improve patient outcomes among women undergoing NSM for breast cancer risk-reduction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None