Melanoma
Conditions
Keywords
metastatic, melanoma, skin cancer, paclitaxel, carboplatin, temozolomide
Brief summary
The number of melanoma cases has been steadily increasing over the past few decades. For many patients with metastatic melanoma, there are no effective therapies. The goal of this study is to determine whether a combination drug treatment of carboplatin, paclitaxel and temozolomide is effective in the treatment of metastatic or recurrent melanoma.
Detailed description
Over the past several decades, significant research has been conducted to try to identify active chemotherapeutic agents for the treatment of melanoma. The rationale for combining taxanes and platinum agents is that both have activity in melanoma; in vitro and clinical data suggest synergy between these drugs when used in combination in a wide variety of tumors, including melanoma; and the toxicity profiles of these agents do not overlap. Temozolomide (a drug approved for the treatment of melanoma) has been combined with other drugs, including taxanes and platinums, in previous clinical trials for melanoma. Specifically, a previous phase I study of the combination of temozolomide, paclitaxel, and carboplatin in melanoma showed objective responses. The efficacy of this combination is now being studied in this phase II trial.
Interventions
DRUGPaclitaxel, carboplatin, temozolomide
Combination chemotherapy was administered for up to 6 cycles
Sponsors
New Mexico Cancer Research Alliance
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients with biopsy proven advanced melanoma are eligible if there is measurable disease. * Patients must have a life expectancy of at least 12 weeks. * Prior surgery, immunotherapy, minimal chemotherapy (1 drug for less than 4 months), or radiotherapy for primary tumor is acceptable but must be completed at least 4 weeks from study entry, and patient should have completely recovered from such procedures. * Patients must have a Zubrod performance status of 0-2. * Patients must sign an informed consent. * Patients should have adequate bone marrow function defined by an absolute peripheral granulocyte count of ≥ 1500 cells/mm3, hemoglobin \> 8 g/dl, platelet count ≥ 100 000/mm3. * Patients should have a normal hepatic function with a total bilirubin \< 1.5 the upper limit of normal (ULN) and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) \< 2 times the upper limit of normal (ULN),and adequate renal function as defined by a serum creatinine ≤ 1.5 times the ULN. * Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and at least for 3 months. * Patients with brain metastases are eligible if they have been appropriately treated, are asymptomatic
Exclusion criteria
* Pregnant women or nursing mothers are not eligible. * Patients must not receive any other concurrent chemotherapy or radiation during this trial. * Patients with severe medical problems that would interfere with the therapy are not eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 6 months | Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Objective Response Rate (ORR) is the sum of the percentages of patients achieving CR or PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 2 years | The time from treatment initiation to death by any cause. |
| Safety Profile | Up to 30 days after last on-study treatment, for up to 2 years | All toxicities encountered during the study by patients who receive at least one on-study treatment will be graded according to the NCI CTCAE (Version 3.0). The number of patients experiencing adverse events will be reported according to grade. |
| Time to Progression | 2 years | The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from sites in the New Mexico Cancer Care Alliance from October, 2009 to March, 2013.
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy Combination Chemotherapy Combination of paclitaxel, carboplatin, temozolomide: Carboplatin at an AUC of 5 on Day 1, paclitaxel at 175 mg/m2 on Day 1, and temozolomide at 125 mg/m2 Day 2-Day 6, on a 28 day cycle.
Paclitaxel, carboplatin, temozolomide: Combination chemotherapy was administered for up to 6 cycles | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Chemotherapy Combination |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Previous Therapy Chemotherapy | 4 participants |
| Previous Therapy Immune Vaccines | 2 participants |
| Previous Therapy Interferon | 5 participants |
| Previous Therapy Radiation | 8 participants |
| Previous Therapy Surgery | 16 participants |
| Race/Ethnicity, Customized Black | 1 participants |
| Race/Ethnicity, Customized White Hispanic | 4 participants |
| Race/Ethnicity, Customized White non-Hispanic | 14 participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 13 Participants |
| Site of Metastasis Bone | 8 participants |
| Site of Metastasis Brain | 1 participants |
| Site of Metastasis Liver | 7 participants |
| Site of Metastasis Lung | 14 participants |
| Site of Metastasis Other visceral organs | 12 participants |
| Site of Metastasis Regional Lymph Nodes | 10 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 14 / 19 |
| serious Total, serious adverse events | 6 / 19 |
Outcome results
Primary
Objective Response Rate (ORR)
Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Objective Response Rate (ORR) is the sum of the percentages of patients achieving CR or PR.
Time frame: 6 months
Population: The 16 patients who completed treatment were evaluable for the endpoint of overall response rate.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy Combination | Objective Response Rate (ORR) | Complete response (CR) | 1 participants |
| Chemotherapy Combination | Objective Response Rate (ORR) | Partial response (PR) | 3 participants |
| Chemotherapy Combination | Objective Response Rate (ORR) | Stable disease | 0 participants |
| Chemotherapy Combination | Objective Response Rate (ORR) | Progressive disease (PD) | 12 participants |
| Chemotherapy Combination | Objective Response Rate (ORR) | ORR (CR + PR) | 4 participants |
Secondary
Overall Survival
The time from treatment initiation to death by any cause.
Time frame: 2 years
Population: The 16 patients who completed treatment were evaluable for survival analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy Combination | Overall Survival | 47 weeks |
Secondary
Safety Profile
All toxicities encountered during the study by patients who receive at least one on-study treatment will be graded according to the NCI CTCAE (Version 3.0). The number of patients experiencing adverse events will be reported according to grade.
Time frame: Up to 30 days after last on-study treatment, for up to 2 years
Population: All patients who had received at least one dose of on-study treatment were evaluable for toxicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy Combination | Safety Profile | Bone pain (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Muscle weakness, lower limb (Grade 1-2) | 2 participants |
| Chemotherapy Combination | Safety Profile | Diarrhea (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Fatigue (Grade 1-2) | 9 participants |
| Chemotherapy Combination | Safety Profile | Fatigue (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Fever (Grade 1-2) | 0 participants |
| Chemotherapy Combination | Safety Profile | Fever (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Weight loss (Grade 1-2) | 0 participants |
| Chemotherapy Combination | Safety Profile | Weight loss (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Anorexia (Grade 1-2) | 1 participants |
| Chemotherapy Combination | Safety Profile | Anorexia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Diarrhea (Grade 1-2) | 5 participants |
| Chemotherapy Combination | Safety Profile | Aspartate aminotransferase increased (Grade 1-2) | 2 participants |
| Chemotherapy Combination | Safety Profile | Aspartate aminotransferase increased (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Vomiting (Grade 1-2) | 2 participants |
| Chemotherapy Combination | Safety Profile | Vomiting (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Gastrointestinal Bleed (Grade 1-2) | 0 participants |
| Chemotherapy Combination | Safety Profile | Gastrointestinal Bleed (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Nausea (Grade 1-2) | 12 participants |
| Chemotherapy Combination | Safety Profile | Nausea (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Alanine aminotransferase increased (Grade 1-2) | 2 participants |
| Chemotherapy Combination | Safety Profile | Alanine aminotransferase increased (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Hyperbilirubinemia (Grade 1-2) | 1 participants |
| Chemotherapy Combination | Safety Profile | Hyperbilirubinemia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Neutropenia (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Neutropenia (Grade 3-4) | 2 participants |
| Chemotherapy Combination | Safety Profile | Anemia (Grade 1-2) | 4 participants |
| Chemotherapy Combination | Safety Profile | Anemia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Lymphopenia (Grade 1-2) | 4 participants |
| Chemotherapy Combination | Safety Profile | Lymphopenia (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Leukopenia (Grade 1-2) | 7 participants |
| Chemotherapy Combination | Safety Profile | Leukopenia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Thrombocytopenia (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Thrombocytopenia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Hyperglycemia (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Hyperglycemia (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Hypophosphatemia (Grade 1-2) | 0 participants |
| Chemotherapy Combination | Safety Profile | Hypophosphatemia (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Hypokalemia (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Hypokalemia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Hyponatremia (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Hyponatremia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Chest wall pain (Grade 1-2) | 1 participants |
| Chemotherapy Combination | Safety Profile | Chest wall pain (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Bone pain (Grade 1-2) | 2 participants |
| Chemotherapy Combination | Safety Profile | Muscle weakness, lower limb (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Joint pain (Grade 1-2) | 1 participants |
| Chemotherapy Combination | Safety Profile | Joint pain (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Drowsiness (Grade 1-2) | 0 participants |
| Chemotherapy Combination | Safety Profile | Drowsiness (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Peripheral Sensory Neuropathy (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Peripheral Sensory Neutropenia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Pericardial effusion (Grade 1-2) | 0 participants |
| Chemotherapy Combination | Safety Profile | Pericardial effusion (Grade 3-4) | 1 participants |
| Chemotherapy Combination | Safety Profile | Edema limbs (Grade 1-2) | 1 participants |
| Chemotherapy Combination | Safety Profile | Edema limbs (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Alopecia (Grade 1-2) | 8 participants |
| Chemotherapy Combination | Safety Profile | Alopecia (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Rash (Grade 1-2) | 4 participants |
| Chemotherapy Combination | Safety Profile | Rash (Grade 3-4) | 0 participants |
| Chemotherapy Combination | Safety Profile | Dry mouth (Grade 1-2) | 3 participants |
| Chemotherapy Combination | Safety Profile | Dry mouth (Grade 3-4) | 0 participants |
Secondary
Time to Progression
The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 2 years
Population: The 16 patients who completed treatment were evaluable for progression-free survival.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Chemotherapy Combination | Time to Progression | 31 weeks |