Stage IV Surgery Versus Best Medical Therapy

Stage IV Resectable Melanoma Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01013623
• Other study ID #: MORD-STG4SURG-0409
• Secondary ID: 3P01CA012582-35S
• Status: Terminated
• Phase: Phase 3
• First received: November 12, 2009
• Last updated: September 24, 2012
• Start date: November 2009
• Est. completion date: September 2012

Study information

• Verified date: September 2012
• Source: John Wayne Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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. Results also will indicate whether Bacillus Calmette-Guerin (BCG) postoperative immunotherapy significantly improves the outcome of patients treated with surgery.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Stage IV Resectable Melanoma

Intervention

Procedure:
• Surgery
surgical resection to remove all known disease
• Surgery plus 2 adjuvant doses of BCG
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.

Other:
• best medical therapy
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.

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	Istituto Nazionale dei Tumori Napoli	Naples
Netherlands	Univesitair Medisch Centrum Groningen	Groningen
United States	Buffalo General Hospital	Buffalo	New York
United States	Rush University	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Dallas Surgical Group	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Penn State Hershey Cancer Center	Hershey	Pennsylvania
United States	IHC Cancer Services Intermountain Healthcare	Murray	Utah
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	John Wayne Cancer Institute	Santa Monica	California
United States	Geisinger Clinic	Wilkes-Barre	Pennsylvania
United States	Wake Forest University	Winston-Salem	North Carolina
United States	Main Line Health System	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
John Wayne Cancer Institute	Melanoma Research Alliance

Countries where clinical trial is conducted

United States,  Australia,  Israel,  Italy,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Defined as time from randomization to death from any cause	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.	No
Secondary	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.	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.	No
Secondary	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.	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.	No
Secondary	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.	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.	No