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

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
temozolomide
flow cytometry
staining method
biopsy
laboratory biomarker analysis
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (individualized chemotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression-Free Survival
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. 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 (Section 11.41). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Overall Survival
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

Full Information

First Posted
March 30, 2011
Last Updated
September 28, 2020
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01328535
Brief Title
Individualized Temozolomide in Treating Patients With Stage IV Melanoma That Cannot Be Removed By Surgery
Official Title
Individualized (Timed) Temozolomide Administration as a Means of Immune Reconstitution in Patients With Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
January 2011 (Actual)
Primary Completion Date
June 22, 2013 (Actual)
Study Completion Date
July 11, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (individualized chemotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
temozolomide
Other Intervention Name(s)
SCH 52365, Temodal, Temodar, TMZ
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
staining method
Other Intervention Name(s)
Staining
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
biopsy
Other Intervention Name(s)
biopsies
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Progression-Free Survival at 4 Months
Description
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 Frame
Time from registration to the earliest date of documentation of disease progression, assessed at 4 months
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Description
Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. 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 (Section 11.41). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame
Up to 2 years
Title
Overall Survival
Description
Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame
Up to 2 years
Title
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Description
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
To Evaluate the Impact of Timed TMZ Chemotherapy on Immune Biomarkers and the Anti-tumor Immune Biorhythms.
Time Frame
6 months
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roxana Dronca, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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