Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery

NCT01328535 | Completed Phase 2 Results DMC

• 3 other identifiers: MC1076NCI-2011-0044910-008497
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial studies individualized temozolomide (TMZ) in treating patients with stage IV melanoma that cannot be removed by surgery. Drugs used in chemotherapy, such as TMZ, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving TMZ at different times, which are determined individually for each patient based on the phase (biorhythm) of the immune system response against the tumor may allow for a better drug response and may kill more tumor cells

Conditions

Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival at 4 Months

  The distribution of time to progression will be estimated using the method of Kaplan-Meier and the 4 month progression-free rate (percentage) will be provided. Progression is defined as: At least one of the following must be true: At least one new malignant lesion, which also includes any lymph node that was normal at baseline (\< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD. In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.

  Time from registration to the earliest date of documentation of disease progression, assessed at 4 months

Secondary Outcomes (3)

• Progression-Free Survival

  Up to 2 years

• Overall Survival

  Up to 2 years

• Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)

  Up to 2 years

Other Outcomes (2)

• To Evaluate the Impact of Timed TMZ Chemotherapy on Immune Biomarkers and the Anti-tumor Immune Biorhythms.

  6 months

• To Evaluate the Parameters of Immune Homeostasis That Are Associated With the Anti-tumor Immune Biorhythm in Order to Gain Insight Into the Mechanism of the Observed Clinical and Immunological Effect of Timed TMZ Chemotherapy

  2 years

Study Arms (1)

Treatment (individualized chemotherapy)

EXPERIMENTAL

Patients with an established biorhythm receive TMZ PO on recommended day for 5 days. Treatment repeats every 21-42 days until disease progression or unacceptable toxicity. Patients without an established biorhythm receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity.

Drug: temozolomide; Other: flow cytometry; Other: staining method; Procedure: biopsy; Other: laboratory biomarker analysis

Interventions

temozolomide DRUG

Given PO

Also known as: SCH 52365, Temodal, Temodar, TMZ

Treatment (individualized chemotherapy)

flow cytometry OTHER

Correlative studies

Treatment (individualized chemotherapy)

staining method OTHER

Correlative studies

Also known as: Staining

Treatment (individualized chemotherapy)

biopsy PROCEDURE

Optional correlative studies

Also known as: biopsies

Treatment (individualized chemotherapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (individualized chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Histologic/cytologic proof of stage IV malignant melanoma not amenable to surgery
• Any number of previous chemotherapy regimens (except those containing TMZ or dacarbazine \[DTIC\]) in the metastatic setting are allowed as long as \>= 4 weeks have elapsed from last treatment
• Measurable disease defined as at least one lesion whose longest diameter can be accurately measured as \>= 1.0 cm with spiral CT scan, or ≥ 2 cm with computed tomography (CT) component of a positron emission tomography (PET)/CT; Note: disease that is measurable by physical examination only is not eligible
• Life expectancy of \>= 3 months
• Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2
• Recovered from side effects that might interfere with the protocol therapy and: - \>= 4 weeks must have elapsed from last radiation treatment to time of study entry - \>= 4 weeks must have elapsed from the last chemotherapy administration to time of study entry
• Absolute neutrophil count (ANC) \>= 1500/mL
• Platelet count \>= 100,000/mcl
• Hemoglobin \>= 9gm/mcl
• Creatinine =\< 2.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) =\< 3 x ULN
• Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to return to Mayo Clinic Rochester for follow-up, except for some appointments that can be made with the local physician
• Patient willing to provide research blood samples

You may not qualify if:

• Receiving any other investigational agents including those for symptom management
• Uncontrolled intercurrent illness including, but not limited to, the following: - Active infection - Congestive heart-failure (New York Heart Association \[NYHA\] grade III or IV)
• Pregnant or breast feeding women, or women of child-bearing potential (and/or their partners) who are unwilling to utilize an approved method of birth control during the study and for 1 month afterward
• History of other malignancy \< 5 years with the exception of basal cell or squamous cell carcinoma of the skin treated with local resection only, limited stage prostate cancer treated with surgery or radiation therapy with currently undetectable prostate-specific antigen (PSA), or carcinoma in situ of the cervix
• Known standard therapy for the patient's disease that is potentially curative or proven capable of extending life expectancy
• Known immunosuppression (i.e. chronic steroid use) or autoimmune disorder
• Human immunodeficiency virus (HIV) positive
• Current or known history of hepatitis
• Previous treatment with DTIC or TMZ
• Previous immunotherapy treatment for metastatic disease in the preceding 2 months; Note: immunotherapy in the adjuvant setting is allowed
• Previously untreated brain metastases; Note: patients with previously treated brain metastases are allowed as long as these are radiologically stable for \>= 3 months and the patient is off steroids for \>= 4 weeks

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Temozolomide; Flow Cytometry; Coloring Agents; Staining and Labeling; Biopsy

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; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Specialty Uses of Chemicals; Chemical Actions and Uses; Histocytological Preparation Techniques; Histological Techniques; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Roxana S. Dronca, M.D.
• Organization: Mayo Clinic

Dronca.Roxana@mayo.edu

507/284-2511

Study Officials

• Roxana Dronca, M.D.

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: April 4, 2011
• Study Start: January 1, 2011
• Primary Completion: June 22, 2013
• Study Completion: July 11, 2018
• Last Updated: October 22, 2020
• Results First Posted: November 7, 2018

Record last verified: 2019-02

Locations

US (1)