Phase II Trial of Neoadjuvant Temozolomide in Melanoma Patients With Palpable Stage III or IV Disease Undergoing Complete Surgical Resection - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center Schering-Plough
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00588341

Purpose

In this study, we want to find out how likely it is for temozolomide to shrink melanoma tumors that have spread only to areas that could be removed by surgery. We also want to study the melanoma before and after temozolomide treatment to learn why some tumors respond and others do not. This is a Phase II trial. This means that it will test a drug - in this case, temozolomide -- that has already been studied and shown to be safe.

Surgery, when possible, is the main treatment for patients with melanoma like yours. In most people, however, melanoma cells have already spread to other places in the body. This means that even with surgery, many people will have the melanoma come back. This is often fatal.

One goal of this trial is to treat the melanoma cells that might have spread before they have a chance to grow.

As part of this trial, we also study which genes are turned on and which genes are turned off in your tumor. We will obtain tumor from the biopsy done before you started temozolomide treatment and from the tumor removed during the surgery done after you finish temozolomide treatment. This may help us understand how temozolomide works and how to recognize which tumors will respond.

Before and during the temozolomide treatment, we will also test a new way of measuring the amount of tumor present. This involves a special way of analyzing the CT scan which you will have anyway. This new technique may allow us to see tumor shrinkage very early in the treatment course.

Condition	Intervention	Phase
Melanoma Skin Cancer Cancer	Drug: Temozolomide	Phase II

MedlinePlus related topics: Cancer Melanoma Skin Cancer Surgery

Drug Information available for: Temozolomide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial of Neoadjuvant Temozolomide in Melanoma Patients With Palpable Stage III or IV Disease Undergoing Complete Surgical Resection

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

Overall objective response rate (CR and PR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Correlation of oligonucleotide array pattern and of methylation of the MGMT promoter and MGMT expression level with response to treatment; of volumetric tumor measurements with standard response criteria and with final pathological findings; Toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment:	24
Study Start Date:	September 2005
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental	Drug: Temozolomide At the start of the trial a core needle biopsy of a palpable tumor will be obtained percutaneously in the office after administration of local anesthesia. Patients will then be treated with TMZ according to the extended dosing schedule of 75mg/m2/day x 6 weeks every 8 weeks. After each cycle, patients will be re-evaluated for response. Responding patients will be offered another cycle of treatment. Patients will be treated until best response, progression of disease, or 6 cycles, whichever comes first. After completing temozolomide treatment, patients will be evaluated for surgical resection. It is expected that, unless there is progression of disease, patients will undergo resection (i.e. therapeutic lymph node dissection). In patients who have a complete clinical response to temozolomide, whether or not to do a subsequent lymph node dissection will be left up to the discretion of the surgeon and the patient.

Arms

Assigned Interventions

Treatment: Experimental

Drug: Temozolomide

At the start of the trial a core needle biopsy of a palpable tumor will be obtained percutaneously in the office after administration of local anesthesia. Patients will then be treated with TMZ according to the extended dosing schedule of 75mg/m2/day x 6 weeks every 8 weeks. After each cycle, patients will be re-evaluated for response. Responding patients will be offered another cycle of treatment. Patients will be treated until best response, progression of disease, or 6 cycles, whichever comes first. After completing temozolomide treatment, patients will be evaluated for surgical resection. It is expected that, unless there is progression of disease, patients will undergo resection (i.e. therapeutic lymph node dissection). In patients who have a complete clinical response to temozolomide, whether or not to do a subsequent lymph node dissection will be left up to the discretion of the surgeon and the patient.

Detailed Description:

In this Phase II trial, chemotherapy-naïve patients with palpable Stage III or Stage IV M1a melanoma scheduled to undergo surgical resection will be treated with TMZ in 8 week cycles according to the extended dosing schedule of 75mg/m2/day x 6 weeks with 2 weeks off. Patients will be treated until maximal response to TMZ and then undergo resection of residual disease. The primary endpoint will be tumor response as measured by the RECIST criteria. Patients will be seen monthly.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Palpable Stage III (N1b, N2b, N2c, or N3) or Stage IV (M1a) cutaneous melanoma. Patient must be a potential candidate for complete surgical resection.
Age ≥ 18 years
Histologic proof of pathology reviewed and confirmed at MSKCC
Measurable disease by RECIST criteria
Determination of surgical resectability by surgeon at MSKCC
No prior chemotherapy for melanoma. Prior interferon, interleukin-2 or vaccine therapy is allowed.
No other concurrent chemotherapy, immunotherapy, or radiotherapy
Karnofsky performance status ≥60
Adequate organ function

Exclusion Criteria:

Uveal or mucosal melanoma
Patients with melanoma deemed not amenable to surgical resection or who are not surgical candidates for medical reasons
Frequent vomiting or medical conditions that could interfere with oral medication intake
Serious infection requiring antibiotics, or nonmalignant medical illnesses that are uncontrolled or whose control might be jeopardized by the complications of this therapy
Pregnancy or nursing
History of HIV infection even if on HAART as TMZ leads to CD4+ T cell leukopenia
Concurrent use of high dose vitamins and herbs
Other on-going investigational therapy, concurrent chemotherapy, immunotherapy or radiotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588341

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Schering-Plough

Investigators

Principal Investigator:

Paul Chapman, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Paul Chapman, MD )
Study ID Numbers:	05-076
Study First Received:	December 26, 2007
Last Updated:	March 18, 2009
ClinicalTrials.gov Identifier:	NCT00588341 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Melanoma
Skin Cancer
Cancer
Temozolamide
TMZ

Study placed in the following topic categories:

Skin Diseases
Anesthetics
Skin Neoplasms
Temozolomide
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors

Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
Nevus
Antineoplastic Agents, Alkylating
Alkylating Agents

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Neoplasms, Nerve Tissue
Skin Neoplasms
Temozolomide
Pharmacologic Actions
Melanoma

Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on May 07, 2009