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Stage IV Surgery Versus Best Medical Therapy (STG4SURG)

Primary Purpose

Stage IV Resectable Melanoma

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Surgery
Surgery plus 2 adjuvant doses of BCG
best medical therapy
Sponsored by
Saint John's Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage IV Resectable Melanoma focused on measuring melanoma, stage IV, resectable, surgery, medical therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • 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:

    1. WBC >3,000/mm3
    2. Lymphocytes >800/mm3
    3. Platelets >100,000/mm3
    4. Creatinine <2.0 mg/dL
    5. Bilirubin <2.0 mg/dL
    6. Alkaline phosphatase < 2X upper limit of normal (ULN)
    7. SGOT < 2X ULN
    8. SGPT < 2X ULN
    9. LDH < 1.5X ULN

Exclusion Criteria:

  • 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.
  • 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

Sites / Locations

  • UC Davis Medical Center
  • John Wayne Cancer Institute
  • Rush University
  • Mayo Clinic Cancer Center
  • Buffalo General Hospital
  • Wake Forest University
  • Ohio State University Medical Center
  • Penn State Hershey Cancer Center
  • Thomas Jefferson University
  • Geisinger Clinic
  • Main Line Health System
  • Dallas Surgical Group
  • UT Southwestern Medical Center at Dallas
  • IHC Cancer Services Intermountain Healthcare
  • Huntsman Cancer Institute
  • Princess Alexandra Hospital
  • Tel-Aviv Sourasky Medical Center
  • Istituto Nazionale dei Tumori Napoli
  • Univesitair Medisch Centrum Groningen

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Best Medical Therapy

Surgery Alone

Surgery + BCG

Arm Description

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.

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.

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).

Outcomes

Primary Outcome Measures

Overall survival
Defined as time from randomization to death from any cause

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
November 12, 2009
Last Updated
September 24, 2012
Sponsor
Saint John's Cancer Institute
Collaborators
Melanoma Research Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT01013623
Brief Title
Stage IV Surgery Versus Best Medical Therapy
Acronym
STG4SURG
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Terminated
Why Stopped
Lack of accrual, lack of continued funding.
Study Start Date
November 2009 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Saint John's Cancer Institute
Collaborators
Melanoma Research Alliance

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IV Resectable Melanoma
Keywords
melanoma, stage IV, resectable, surgery, medical therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Best Medical Therapy
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Surgery Alone
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Surgery + BCG
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
surgical resection to remove all known disease
Intervention Type
Procedure
Intervention Name(s)
Surgery plus 2 adjuvant doses of BCG
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
best medical therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Description
Defined as time from randomization to death from any cause
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.
Secondary Outcome Measure Information:
Title
Time to progression of initial metastatic sites (progression-free survival)
Description
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.
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.
Title
Melanoma-specific survival
Description
Defined as time from randomization to death due to melanoma. Death due to causes other than melanoma are not considered events for this analysis.
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.
Title
Time to development of new metastatic sites.
Description
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.
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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 Exclusion Criteria: 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. 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donald L. Morton, MD
Organizational Affiliation
Saint John's Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
John Wayne Cancer Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Rush University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Buffalo General Hospital
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Wake Forest University
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Penn State Hershey Cancer Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Geisinger Clinic
City
Wilkes-Barre
State/Province
Pennsylvania
ZIP/Postal Code
18711
Country
United States
Facility Name
Main Line Health System
City
Wynnewood
State/Province
Pennsylvania
ZIP/Postal Code
19096
Country
United States
Facility Name
Dallas Surgical Group
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
UT Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9155
Country
United States
Facility Name
IHC Cancer Services Intermountain Healthcare
City
Murray
State/Province
Utah
ZIP/Postal Code
84157
Country
United States
Facility Name
Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Princess Alexandra Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Tel-Aviv Sourasky Medical Center
City
Tel-Aviv
ZIP/Postal Code
94239
Country
Israel
Facility Name
Istituto Nazionale dei Tumori Napoli
City
Naples
ZIP/Postal Code
80121
Country
Italy
Facility Name
Univesitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands

12. IPD Sharing Statement

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Stage IV Surgery Versus Best Medical Therapy

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