Paclitaxel and Carboplatin or Temozolomide in Treating Patients With Stage IV Melanoma

Melanoma (Skin) Clinical Trial

Official title:

Releasing the Cancer Patient's Immune System From Down-regulation With Timed Delivery of Standard Chemotherapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00568451
• Other study ID #: MC057F
• Secondary ID: P30CA015083MC057
• Status: Terminated
• Phase: Phase 2
• First received: December 5, 2007
• Last updated: November 25, 2015
• Start date: June 2006
• Est. completion date: April 2012

Study information

• Verified date: March 2014
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving paclitaxel together with carboplatin is more effective than giving temozolomide alone in treating patients with melanoma.

PURPOSE: This phase II trial is studying the side effects and how well giving paclitaxel together with carboplatin or giving temozolomide alone works in treating patients with stage IV melanoma.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: April 2012
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Drug:
• carboplatin
AUC=2 intravenously on days 1, 8 and 15. Re-treat every 4 weeks until progression, unacceptable toxicity, or refusal
• paclitaxel
100mg/m^2 intravenously on days 1, 8 and 15. Re-treat every 4 weeks until progression, unacceptable toxicity, or refusal
• temozolomide
150mg/m^2 at cycle 1, 200mg/m^2 at cycle 2 and beyond, orally on days 1-5. Re-treat every 4 weeks until progression, unacceptable toxicity, or refusal. One treatment cycle=four weeks

Locations

Country	Name	City	State
United States	Mayo Clinic Cancer Center	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment	No
Secondary	Time to Disease Progression	Time to disease progression was defined as the time from registration to documentation of disease progression. Disease progression was measured according to the RECIST criteria. Progression: At least a 20 percent increase in the sum of of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	up to 2 years	No
Secondary	Survival Time	Survival time was defined as the time from registration to death due to any cause.	up to 2 years	No
Secondary	Duration of Response for All Evaluable Patients Who Have Achieved an Objective Response	Duration of response was defined as the date at which the participant's objective status was first noted to be either a Complete Response or Partial Response to the date the progression was documented.	up to 2 years	No
Secondary	Number of Participants Who Experienced Changes in Immunologic Profile (CD4/CD25+ Cells, CD4/Fox-p3+ T Cells) Within a Treatment	Time series plot of the number of circulating cells will be constructed. The resulting plots will be visually inspected for trends within and between treatments. For each cell type, a point and an interval estimate of the number of participants (receiving a given treatment) who had at least a 2-fold increase in the number of circulating cells of that type will be constructed using the properties of the binomial distribution.	up to 2 years	No
Secondary	Number of Participants Who Experienced Changes in Immunologic Profile (MART-1, Tyrosinase, and gp100) Within a Treatment	For those patients who are HLA-A2+, the maximum post-treatment levels of MART-1, tyrosinase, and gp100 will be determined. For each of these specific melanoma specific antigens, the number of participants (within a given treatment) who gained or maintained immunity based on the maximum post-treatment level of that specific melanoma specific antigen will be determined.	up to 2 years	No
Secondary	Number of Participants Who Experienced Changes in Immunologic Profile (IFN? Producing Peptide Specific CTLs) Within a Treatment	For each patient, a time series plot of the number of IFN? producing peptide specific CTLs will be constructed. The resulting plots will be visually inspected for trends within and between treatments. A point and an interval estimate of the number of participants (receiving a given treatment) who had at least a 2-fold increase in the number of the number of IFN? producing peptide specific CTLs will be constructed using the properties of the binomial distribution.	up to 2 years	No