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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01328535
First received: March 30, 2011
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

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


Condition Intervention Phase
Recurrent Melanoma
Stage IV Melanoma
Drug: temozolomide
Other: flow cytometry
Other: staining method
Procedure: biopsy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Individualized (Timed) Temozolomide Administration as a Means of Immune Reconstitution in Patients With Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • To assess the clinical activity of timed administration of TMZ therapy in patients with stage IV melanoma [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Estimated by the number of eligible patients who remain on study and have not progressed at their 4 month evaluation divided by the total number of evaluable patients; a confidence interval for the true 4 month PFS rate is constructed using the properties of the binomial distribution


Secondary Outcome Measures:
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To assess the toxicity profile of timed administration of TMZ therapy in patients with stage IV melanoma who have or have not received prior chemotherapy for their metastatic disease [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the impact of timed TMZ chemotherapy on immune biomarkers and the anti-tumor immune biorhythms. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 59
Study Start Date: January 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (individualized chemotherapy)
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
Given PO
Other Names:
  • SCH 52365
  • Temodal
  • Temodar
  • TMZ
Other: flow cytometry
Correlative studies
Other: staining method
Correlative studies
Other Name: Staining
Procedure: biopsy
Optional correlative studies
Other Name: biopsies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES: I. To assess the clinical activity of timed administration of TMZ therapy in patients with stage IV melanoma who have or have not received prior chemotherapy for metastatic melanoma. SECONDARY OBJECTIVES: I. To assess the toxicity profile of timed administration of TMZ therapy in patients with stage IV melanoma who have or have not received prior chemotherapy for their metastatic disease. II. 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. III. To evaluate the impact of timed TMZ chemotherapy on immune biomarkers and the anti-tumor immune biorhythms. OUTLINE: Prior to initiation of therapy patients will undergo a period of immunologic monitoring to analyze the bioperiodicity of their anti-tumor immune response. Patients with an established biorhythm will receive TMZ orally (PO) starting on the recommended day for 5 days. Treatment repeats every 21-42 days (based on the established biorhythm) until of disease progression or unacceptable toxicity. Patients without an established biorhythm are given the option to go off study or receive TMZ PO on days 1-5. Courses repeat every 28 days until disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for up to 2 years.

  Eligibility

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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01328535

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Roxana Dronca, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01328535     History of Changes
Other Study ID Numbers: MC1076, NCI-2011-00449, MC1076, 10-008497
Study First Received: March 30, 2011
Last Updated: September 12, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014