Releasing the Cancer Patient's Immune System From Down-regulation With Timed Delivery of Standard Chemotherapy
18 Years
N/A
Both
Melanoma (Skin)
Trial Information
Releasing the Cancer Patient's Immune System From Down-regulation With Timed Delivery of Standard Chemotherapy
OBJECTIVES:
- To assess the anti-tumor activity and toxicity profile of timed delivery of
conventional paclitaxel and carboplatin (PC) in patients with stage IV melanoma who
have received prior chemotherapy for their metastatic disease.
- To assess the anti-tumor activity and toxicity profile of timed delivery of
conventional temozolomide (TMZ) chemotherapy in patients with stage IV melanoma who
have received prior chemotherapy for their metastatic disease.
- To assess the anti-tumor activity and toxicity profile of timed delivery of
conventional PC in patients with stage IV melanoma who have not received prior
chemotherapy for their metastatic disease.
- To assess the anti-tumor activity and toxicity profile of timed delivery of
conventional TMZ chemotherapy in patients with stage IV melanoma who have not received
prior chemotherapy for their metastatic disease.
- To evaluate the changes of T-regulator cells, melanoma-specific functional parameters
as a function of time in all four patient cohorts.
OUTLINE: Patients are stratified according to prior chemotherapy for metastatic disease (yes
vs no) and scheduled chemotherapy regimen (paclitaxel and carboplatin vs temozolomide).
Beginning at the predicted day of C-reactive peptide (CRP) peak levels, patients receive
paclitaxel IV and carboplatin IV on days 1, 8, and 15 OR oral temozolomide alone on days
1-5. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable
toxicity.
Patients undergo blood sample collection periodically for pharmacological studies. Samples
are analyzed for CRP quantification via ELISA; presence and number of circulating blood
T-regulator cells via immunophenotyping for CD4/CD25+ and CD4/fox-p3+ T cells; level of
functional immunity against melanoma specific antigens (MART-1, tyrosinase, and gp100) and
survivin in patients that are HLA-A2+ via intracellular staining; total number of cytotoxic
T lymphocytes (CTLs) capable of reacting against melanoma targets via tetramer staining
(Becton-Coulter); and quantification of interferon γ-producing, peptide-specific CTLs via
multicolor conventional flow cytometry.
After completion of study treatment, patients are followed every 3 months for up to 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed metastatic melanoma
- Stage IV disease
- Progressive disease
- No known standard therapy that is potentially curative or proven capable of
extending life expectancy exists
- Planning to undergo chemotherapy with paclitaxel and carboplatin OR temozolomide
alone for progressive disease
- Measurable disease as defined by RECIST criteria
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 3 months
- ANC ≥ 1,500/mL
- Platelet count ≥ 100,000/mL
- Hemoglobin ≥ 9 g/dL
- Creatinine ≤ 2.5 x upper limit of normal (ULN)
- AST ≤ 3 x ULN
- Alkaline phosphatase ≤ 3.0 x ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 1 month after
completion of study therapy
- No uncontrolled intercurrent illness including, but not limited to, any of the
following:
- Active infection
- NYHA class III or IV congestive heart failure
- No history of other malignancy within the past 5 years except for basal cell or
squamous cell carcinoma of the skin treated with local resection only or carcinoma in
situ of the cervix
- Willing to provide research blood samples
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- At least 4 weeks since prior radiotherapy
- At least 4 weeks since prior chemotherapy (patients who received chemotherapy in the
metastatic setting)
- No prior chemotherapy treatment with agents similar to study drugs
- No prior chemotherapy in the metastatic setting (for chemo-naive patients)
- No concurrent enrollment in a different clinical study in which investigational
procedures or agents are being used
- No other concurrent investigational agents
- No other concurrent chemotherapy or radiotherapy, including palliative radiotherapy
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants With an Objective Tumor Status of Either a Complete Response(CR) or Partial Response (PR), According to RECIST (Response Evaluation Criteria in Solid Tumors) Criteria
Outcome Description:
Response that was noted on 2 consecutive evaluations for at least 4 weeks apart. CR: Disappearance of all target lesions; PR: At least a 30 percent of decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Target lesions: All measurable lesions up to a maximum of 10 lesions representative of all involved organs.
Outcome Time Frame:
Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment
Safety Issue:
No
Principal Investigator
Svetomir Markovic, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000578996
NCT ID:
NCT00568451
Start Date:
June 2006
Completion Date:
December 2011
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
