Stage IV Resectable MelanomaPhase 3STG4SURGNCT01013623
Stage IV Surgery Versus Best Medical Therapy
A Phase 3 study testing Surgery, Surgery plus 2 adjuvant doses of BCG and best medical therapy in people with Stage IV Resectable Melanoma, run by Saint John's Cancer Institute at 19 sites in 5 countries.
Trial summary
This study will establish the role of surgical versus nonsurgical approaches in patients whose melanoma has spread to distant sites. Results will help clinicians develop a standardized initial approach that prolongs survival and optimizes quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Resectable Melanoma
- What is being tested?
- Surgery, Surgery plus 2 adjuvant doses of BCG and best medical therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 19 sitesin 5 countries
- Study dates
- Nov 2009to Sep 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must provide informed written consent for participation.
- At least 18 years of age
- Have a minimum life expectancy (excluding melanoma) of 5 years.
- All known disease must be surgically resectable in the opinion of a participating surgeon.
- Must have a histologic diagnosis of Stage IV melanoma arising from a primary cutaneous site or visceral metastasis from an unknown primary site and be within 4 months of initial stage IV diagnosis.
- Up to 3 visceral organs involved
Show all 19Show fewer
- Up to 6 lesions allowed
- Must have ECOG performance status of 0 or 1.
- Must be in good general health with no serious co-morbid illness. Good clinical judgment must be exercised in careful selection of patients who are candidates for surgical resection of distant metastases.
- Laboratory values within 30 days of randomization:
- WBC >3,000/mm3
- Lymphocytes >800/mm3
- Platelets >100,000/mm3
- Creatinine <2.0 mg/dL
- Bilirubin <2.0 mg/dL
- Alkaline phosphatase < 2X upper limit of normal (ULN)
- SGOT < 2X ULN
- SGPT < 2X ULN
- LDH < 1.5X ULN
Who cannot join
- Unresectable metastatic disease or more than 4 months since stage IV diagnosis.
- Brain or bone metastatic sites.
- History of primary uveal or mucosal melanoma.
- Another concomitant diagnosis that limits life expectancy to less than 5 years.
- Chronic immunosuppression due to inherited, acquired or iatrogenic immune defect. This includes active HIV, hepatitis, or use of immunosuppressive medications as a component of anti-rejection therapy for organ transplant, as treatment for an autoimmune disease.
- More than 3 involved visceral organ sites or more than 6 metastatic lesions.
Show all 10Show fewer
- Psychiatric disorder or organic brain syndrome that might preclude participation in the protocol.
- Diagnosis of other malignancy in the past 5 years except adequately treated low grade malignancies such as basal cell carcinoma, cutaneous squamous cell carcinoma, carcinoma-in-situ of the cervix, or other neoplasm that will not limit life expectancy to less than 5 years.
- Serious cardiac, gastrointestinal, hepatic or pulmonary disease that would make surgical resection high-risk.
- Pregnancy
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
United States15 sites
Buffalo General Hospital
Buffalo, New York, 14203
Rush University
Chicago, Illinois, 60612
Ohio State University Medical Center
Columbus, Ohio, 43210
Dallas Surgical Group
Dallas, Texas, 75235
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75390-9155
Penn State Hershey Cancer Center
Hershey, Pennsylvania, 17033
IHC Cancer Services Intermountain Healthcare
Murray, Utah, 84157
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
UC Davis Medical Center
Sacramento, California, 95817
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
John Wayne Cancer Institute
Santa Monica, California, 90404
Geisinger Clinic
Wilkes-Barre, Pennsylvania, 18711
Wake Forest University
Winston-Salem, North Carolina, 27157
Main Line Health System
Wynnewood, Pennsylvania, 19096
Netherlands1 site
Univesitair Medisch Centrum Groningen
Groningen, 9700 RB
About this study
Official title: A Phase III, Randomized Trial of Surgical Resection With or Without BCG Versus Best Medical Therapy as Initial Treatment in Stage IV Melanoma
This study will establish the role of surgical versus nonsurgical approaches in patients whose melanoma has spread to distant sites. Results will help clinicians develop a standardized initial approach that prolongs survival and optimizes quality of life. Results also will indicate whether Bacillus Calmette-Guerin (BCG) postoperative immunotherapy significantly improves the outcome of patients treated with surgery.
Read the detailed description
This study is designed to examine the impact of surgical resection versus medical therapy as initial treatment therapy for patients with Stage IV melanoma. Surgical resection is thought to be efficacious in highly selected patients with solitary metastases, but not in patients with multiple sites of metastases. Even in those with solitary metastases, there is considerable debate among major melanoma centers over whether undergoing initial systemic medical therapy prior to surgical resection should be preferred to initial surgical resection upon Stage IV diagnosis. According to Dr. Dan Coit, Co-leader of the Melanoma Disease Management Team at Memorial Sloan Kettering Cancer Institute in New York, a trial of initial medical therapy is their standard approach on the multidisciplinary melanoma service even for patients with solitary distant metastases (personal communication, 15 Dec 2009).
Many who favor upfront medical therapy believe that delay before surgical resection may avoid unnecessary surgery by identifying patients who progress early due to the outgrowth of occult metastases at multiple sites, which may make the patient unresectable.
This is a Phase III, randomized, international, multicenter study of metastasectomy with or without BCG versus best medical therapy as initial therapy in Stage IV melanoma. This study has three arms: surgical resection plus BCG as an immune adjuvant, surgical resection plus observation, and best medical therapy (BMT). Since no systemic medical therapy has been demonstrated to be superior to DTIC and multiple new therapies are being evaluated, the choice as to what constitutes best medical therapy will be determined by the individual investigator based on the standard of care for systemic medical therapy at that particular multicenter site. Best systemic medical therapy may include clinical trials of new agents or standard non-protocol treatments (e.g., DTIC or Temodar according to the standard of care at the multi-center site).
Patients who progress on the best medical treatment arm may switch to a different medical therapy or, if appropriate, have surgical therapy; similarly, surgery patients may have additional surgical resection or receive medical therapy.
- Conditions
- Stage IV Resectable Melanoma
- Being tested
- Surgery, Surgery plus 2 adjuvant doses of BCG, best medical therapy
- Keywords
- melanoma, stage IV, resectable, surgery, medical therapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SurgeryProcedure or surgery
surgical resection to remove all known disease
Surgery plus 2 adjuvant doses of BCGProcedure or surgery
Patients in the surgical resection + BCG arm will have an additional two visits to receive BCG. The first dose of BCG will be given no earlier than 4 weeks after surgery, and the second BCG dose will follow 2 weeks later. The actual doses are determined by the patient's pre-study tuberculin-reactivity status. Patients with a pre-study PPD induration of ≥10 mm will be given half the normal dose of BCG. Those with PPD induration of ≥20 mm will be given 25% of the normal dose.
best medical therapyOther
Patients randomized to the Best Medical Therapy arm will decide on a course of medical therapy based on what the patient's medical oncologists feels is best for the patient. Best systemic medical therapy may include clinical trials of new agents or standard non-protocol treatments. Patients who progress on the best medical treatment arm may switch to a different medical therapy or, if still appropriate, may receive surgery.
| Study group | Role | What they receive |
|---|---|---|
| Best Medical Therapy | Active comparator | The best medical therapy group will not initially undergo surgery, but will be treated with the therapy that medical oncologists or surgeons feel is best for the patient. This treatment may include standard or experimental therapies. Receives: Other: best medical therapy |
| Surgery Alone | Active comparator | The surgery alone group will undergo complete resection (surgical removal) of all known disease, if possible. After surgery, patients will be followed regularly and monitored for disease recurrence. Receives: Procedure: Surgery |
| Surgery + BCG | Active comparator | The Surgery + BCG group will first have a complete resection (surgical removal) of all known disease, if possible. After recovery from surgery, two doses of BCG will be given two weeks apart. Each dose is given as 8 separate injections into the skin (called intradermal injections). Receives: Procedure: Surgery plus 2 adjuvant doses of BCG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Defined as time from randomization to death from any cause
Measured: 3 interim analyses will be conducted when 75, 148, and 217 events (deaths) have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Secondary outcomes (3)
Time to progression of initial metastatic sites (progression-free survival)
For this study, PFS is defined as the time from randomization to disease recurrence at initial metastatic site in patients rendered disease-free by surgery, or time from randomization to RECIST-defined progression of target lesions in patients receiving best medical therapy or those having residual disease following surgery.
Measured: 3 interim analyses will be conducted when 75, 148, and 217 primary events have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Melanoma-specific survival
Defined as time from randomization to death due to melanoma. Death due to causes other than melanoma are not considered events for this analysis.
Measured: 3 interim analyses will be conducted when 75, 148, and 217 recurrences/progressions have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Time to development of new metastatic sites.
This endpoint is defined as the time from randomization to disease recurrence at new metastatic sites in patients rendered disease-free by surgery, or time from randomization to the development of new metastatic sites of disease in patients in the best medical therapy group. Progression of existing lesions in the best medical therapy arm will not be considered an event for this endpoint.
Measured: 3 interim analyses will be conducted when 75, 148, and 217 primary events have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2009 (estimated)
- Study startNov 2009
- Primary completionSep 2012
- Study completionSep 2012
Why it stopped: Lack of accrual, lack of continued funding.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV Resectable MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Saint John's Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Melanoma Research Alliance
- Responsible party
- Sponsor
- Investigators
- Donald L. Morton, MD, Study chair, Saint John's Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01013623
- Sponsor's protocol ID
- MORD-STG4SURG-0409
- Other IDs
- 3P01CA012582-35S1
- Acronym
- STG4SURG
- Status last verified
- Sep 2012
- First submitted
- 12 Nov 2009
- Last updated
- 26 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized Trial of Surgical Resection With or Without BCG Versus Best Medical Therapy as Initial Treatment in Stage IV Melanoma
- ClinicalTrials.gov ID
- NCT01013623
- Acronym / sponsor ID
- STG4SURG / MORD-STG4SURG-0409
- Conditions
- Stage IV Resectable Melanoma
- Keywords
- melanoma, stage IV, resectable, surgery, medical therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual, lack of continued funding.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Saint John's Cancer InstituteUniversity, hospital or other
- Collaborators
- Melanoma Research Alliance
- Study start
- Nov 2009
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 16 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will establish the role of surgical versus nonsurgical approaches in patients whose melanoma has spread to distant sites. Results will help clinicians develop a standardized initial approach that prolongs survival and optimizes quality of life. Results also will indicate whether Bacillus Calmette-Guerin (BCG) postoperative immunotherapy significantly improves the outcome of patients treated with surgery.
Detailed description
This study is designed to examine the impact of surgical resection versus medical therapy as initial treatment therapy for patients with Stage IV melanoma. Surgical resection is thought to be efficacious in highly selected patients with solitary metastases, but not in patients with multiple sites of metastases. Even in those with solitary metastases, there is considerable debate among major melanoma centers over whether undergoing initial systemic medical therapy prior to surgical resection should be preferred to initial surgical resection upon Stage IV diagnosis. According to Dr. Dan Coit, Co-leader of the Melanoma Disease Management Team at Memorial Sloan Kettering Cancer Institute in New York, a trial of initial medical therapy is their standard approach on the multidisciplinary melanoma service even for patients with solitary distant metastases (personal communication, 15 Dec 2009).
Many who favor upfront medical therapy believe that delay before surgical resection may avoid unnecessary surgery by identifying patients who progress early due to the outgrowth of occult metastases at multiple sites, which may make the patient unresectable.
This is a Phase III, randomized, international, multicenter study of metastasectomy with or without BCG versus best medical therapy as initial therapy in Stage IV melanoma. This study has three arms: surgical resection plus BCG as an immune adjuvant, surgical resection plus observation, and best medical therapy (BMT). Since no systemic medical therapy has been demonstrated to be superior to DTIC and multiple new therapies are being evaluated, the choice as to what constitutes best medical therapy will be determined by the individual investigator based on the standard of care for systemic medical therapy at that particular multicenter site. Best systemic medical therapy may include clinical trials of new agents or standard non-protocol treatments (e.g., DTIC or Temodar according to the standard of care at the multi-center site).
Patients who progress on the best medical treatment arm may switch to a different medical therapy or, if appropriate, have surgical therapy; similarly, surgery patients may have additional surgical resection or receive medical therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Best Medical Therapy | Active comparator | Other: best medical therapyThe best medical therapy group will not initially undergo surgery, but will be treated with the therapy that medical oncologists or surgeons feel is best for the patient. This treatment may include standard or experimental therapies. |
| Surgery Alone | Active comparator | Procedure: SurgeryThe surgery alone group will undergo complete resection (surgical removal) of all known disease, if possible. After surgery, patients will be followed regularly and monitored for disease recurrence. |
| Surgery + BCG | Active comparator | Procedure: Surgery plus 2 adjuvant doses of BCGThe Surgery + BCG group will first have a complete resection (surgical removal) of all known disease, if possible. After recovery from surgery, two doses of BCG will be given two weeks apart. Each dose is given as 8 separate injections into the skin (called intradermal injections). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients must provide informed written consent for participation.
- At least 18 years of age
- Have a minimum life expectancy (excluding melanoma) of 5 years.
- All known disease must be surgically resectable in the opinion of a participating surgeon.
- Must have a histologic diagnosis of Stage IV melanoma arising from a primary cutaneous site or visceral metastasis from an unknown primary site and be within 4 months of initial stage IV diagnosis.
Key exclusion criteria (10 listed)
- Unresectable metastatic disease or more than 4 months since stage IV diagnosis.
- Brain or bone metastatic sites.
- History of primary uveal or mucosal melanoma.
- Another concomitant diagnosis that limits life expectancy to less than 5 years.
- Chronic immunosuppression due to inherited, acquired or iatrogenic immune defect. This includes active HIV, hepatitis, or use of immunosuppressive medications as a component of anti-rejection therapy for organ transplant, as treatment for an autoimmune disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgerysurgical resection to remove all known disease | Procedure or surgery | Surgery Alone |
| Surgery plus 2 adjuvant doses of BCGPatients in the surgical resection + BCG arm will have an additional two visits to receive BCG. The first dose of BCG will be given no earlier than 4 weeks after surgery, and the second BCG dose will follow 2 weeks later. The actual doses are determined by the patient's pre-study tuberculin-reactivity status. Patients with a pre-study PPD induration of ≥10 mm will be given half the normal dose of BCG. Those with PPD induration of ≥20 mm will be given 25% of the normal dose. | Procedure or surgery | Surgery + BCG |
| best medical therapyPatients randomized to the Best Medical Therapy arm will decide on a course of medical therapy based on what the patient's medical oncologists feels is best for the patient. Best systemic medical therapy may include clinical trials of new agents or standard non-protocol treatments. Patients who progress on the best medical treatment arm may switch to a different medical therapy or, if still appropriate, may receive surgery. | Other | Best Medical Therapy |
Primary outcome
Overall survival
Time frame: 3 interim analyses will be conducted when 75, 148, and 217 events (deaths) have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Defined as time from randomization to death from any cause
3 secondary outcomes
Time to progression of initial metastatic sites (progression-free survival)
Time frame: 3 interim analyses will be conducted when 75, 148, and 217 primary events have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Melanoma-specific survival
Time frame: 3 interim analyses will be conducted when 75, 148, and 217 recurrences/progressions have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Time to development of new metastatic sites.
Time frame: 3 interim analyses will be conducted when 75, 148, and 217 primary events have occurred. The final analysis will be conducted when all 284 expected events have occurred.
Results and safety
The study was stopped early (reason given: Lack of accrual, lack of continued funding.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2012.
Related trials for Stage IV Resectable Melanoma
Active, not recruitingPhase 2
Neoadjuvant PD-1 Inhibitor Dostarlimab (TSR-042) vs. Combination of Tim-3 Inhibitor Cobolimab (TSR-022) and PD-1 Inhibitor Dostarlimab (TSR-042) in Melanoma
Melanoma Stage III, Melanoma Stage IV
Active, not recruitingPhase 2
A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma
Melanoma
RecruitingObservational study
Follow-up of a National Cohort of Melanoma Resectable Stage II, Stage III or IV Patients or Unresectable Primary
Malignant Melanoma
RecruitingPhase 2
NeoLIPA: Neoadjuvant LTX-315 in Combination with Pembrolizumab in Resectable Stage III/IV Melanoma
Melanoma Stage IIIB-IV
Not yet recruitingEarly Phase 1
Allogeneic Gammadelta T Cells Combined With Interferon-α1b or PD-1 Monoclonal Antibody in Stage III-IV Amenable to Surgical Resection Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donald L. Morton, MD study chair
Saint John's Cancer Institute
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Surgery, Surgery plus 2 adjuvant doses of BCG and best medical therapy in people with Stage IV Resectable Melanoma, run by Saint John's Cancer Institute at 19 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, Australia, Israel, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of accrual, lack of continued funding.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 3 interim analyses will be conducted when 75, 148, and 217 events (deaths) have occurred. The final analysis will be conducted when all 284 expected events have occurred.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2012.