Temozolomide Alone or With Pegylated Interferon-Alpha 2b (PGI) in Melanoma Patients

NCT00525031 | Completed Phase 2 Results DMC

• 2 other identifiers: 2005-0143NCI-2010-00855
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if temozolomide alone or given with pegylated interferon alpha-2b can help to control metastatic melanoma. Researchers also want to study the safety of these 2 treatments. Objectives:

1. 1.To determine the anti-tumor activity (pathological response CR+PR) and toxicity of temozolomide (TMZ) alone or in combination with pegylated interferon alpha-2b (PGI) in patients with resectable stage IIIC or stage IV (M1a) metastatic melanoma prior to definitive surgical resection.
2. 2.To determine the relapse-free survival, overall survival and the impact of tumor response to chemotherapy in these patients.
3. 3.To differentiate the in vivo treatment effects of TMZ alone vs.TMZ plus PGI and correlate with clinical outcome by analysis the pre- and post-treatment tumors and peripheral blood mononuclear cells with respect to:

Conditions

Melanoma

Keywords

Melanoma; Temozolomide; Temodar; Pegylated Interferon Alpha-2b; PEG-Intron; PGI; Resectable metastatic melanoma; Surgery

Outcome Measures

Primary Outcomes (2)

• Response to Neoadjuvant Therapy by Therapy Arms: Clinical Response Rates (CR + PR + SD)

  Response to neoadjuvant therapy reported as number of participants with clinical response, defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD). Clinical Complete Response (CR): Disappearance of all clinical evidence of visible tumor. Partial Response (PR) : 30% or \> decrease in the sum of the of the longest diameter of target lesions, taking as reference the baseline sum longest diameter persisting for at least 4 weeks. Progressive Disease (PD): \> 20% increase in sum of longest diameter of target lesions, reference baseline sum longest diameter. Appearance new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, reference smallest sum longest diameter since treatment started.

  Evaluated after a total of 8 weeks of therapy before definitive surgery.

• Response to Neoadjuvant Therapy: Overall Clinical Responses

  Response to neoadjuvant therapy reported as number of participants with clinical response, defined as Clinical Complete Response (CR): Disappearance of all clinical evidence of visible tumor. Partial Response (PR) : 30% or \> decrease in the sum of the of the longest diameter of target lesions, taking as reference the baseline sum longest diameter persisting for at least 4 weeks. Progressive Disease (PD): \> 20% increase in sum of longest diameter of target lesions, reference baseline sum longest diameter. Appearance new lesions and/or unequivocal progression of existing non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, reference smallest sum longest diameter since treatment started.

  Evaluated after a total of 8 weeks of therapy before definitive surgery.

Study Arms (2)

Temozolomide (TMZ)

EXPERIMENTAL

Temozolomide = TMZ - 150 mg/m\^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.

Drug: Temozolomide (TMZ)

Temozolomide (TMZ) + Pegylated Interferon-alpha 2b (PGI)

EXPERIMENTAL

Temozolomide = TMZ and PGI = Pegylated Interferon-alpha 2b Temozolomide 150 mg/m\^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks. Pegylated Interferon-alpha 2b 0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.

Drug: Temozolomide (TMZ); Drug: Pegylated Interferon Alpha-2b (PGI)

Interventions

Temozolomide (TMZ) DRUG

150 mg/m\^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.

Also known as: Temodar

Temozolomide (TMZ); Temozolomide (TMZ) + Pegylated Interferon-alpha 2b (PGI)

Pegylated Interferon Alpha-2b (PGI) DRUG

0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.

Also known as: PEG-Intron

Temozolomide (TMZ) + Pegylated Interferon-alpha 2b (PGI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically documented diagnosis of melanoma metastases.
• Stage IIIB/IIIC (N2b, N2c and N3) or stage IV (M1a) melanoma patients with measurable and potentially resectable metastases without clinical and radiological evidence of other distant metastases.
• An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Age 18 or older.
• Adequate organ function defined as follows: a.) Absolute granulocytes greater than or equal to 1,000/mm\^3 and Platelets greater than or equal to 100,000/mm\^3, b.) Serum bilirubin and serum creatinine of less than or equal to 1.5 times upper limit of laboratory normal. If serum creatinine is greater than 1.5 times upper limit of laboratory normal, the urine creatinine clearance must be greater than 60 ml/min., c.) serum glutamate oxaloacetate transaminase (SGOT) (AST), serum glutamate pyruvate transaminase (SGPT) (ALT) and alkaline phosphatase less than or equal to 3 times upper limit of laboratory normal.
• Patients have not had any previous systemic chemotherapy for metastatic melanoma. Prior biologic therapy, targeted therapy or immunotherapy are allowable, but must be at least 2 weeks since prior therapy before starting study drugs. No other concurrent chemotherapy, immunotherapy, or radiotherapy.
• Prior radiation therapy used to enhance local regional control is permitted, but must be at least 2 weeks since prior therapy before starting study drugs. In addition, the patient must have unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity. Lesions within the prior field of radiation may only be used as indicator lesions if there has been recent evidence of disease progression after .
• Ability to understand and sign an informed consent form, indicating awareness of the investigational nature of this study.

You may not qualify if:

• Significant cardiac or pulmonary dysfunction, such as a history of severe cardiovascular disease, myocardial infarction within 6 months of the start of treatment, unstable angina, Class III or Class IV congestive heart failure, ventricular arrhythmia, or any uncontrolled arrhythmia.
• Current significant psychiatric illness.
• Serious infection requiring intravenous antibiotics, or any non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by complications of this therapy.
• Frequent vomiting or any medical condition (e.g. partial bowel obstruction) that could interfere with oral medication intake.
• Autoimmune or immunosuppressive disorders (e.g. HIV or AIDS-related illness).
• Patients who require therapy with systemic corticosteroids.
• No evidence of active secondary malignancy that requires chemotherapy within the past 2 years (excluding non-melanoma skin cancer, and/or all carcinoma in-situ)
• Pregnant or lactating women are ineligible. Women of childbearing potential must have a negative urine pregnancy test within a week of initiation of therapy. All patients must agree to use medically approved contraceptive measures to prevent pregnancy during treatment.
• Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Schering-Plough: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.

  PMID: 36648215 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

Temozolomide; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Wen-Jen Hwu, MD/Professor, Melanoma Medical Oncology
• Organization: UT MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-792-7734

Study Officials

• Wen-Jen Hwu, MD PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 5, 2007
• Study Start: August 1, 2006
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: September 23, 2020
• Results First Posted: July 2, 2017

Record last verified: 2020-09

Locations

US (1)