Neoplasms, Unknown Primary
Conditions
Keywords
Neoplasms, Unknown Primary
Brief summary
In this randomized trial, we will investigate the activity and toxicity of two active regimens, gemcitabine/irinotecan and paclitaxel/carboplatin/Etoposide (both followed by ZD1839) in the first-line treatment of patients with carcinoma of unknown primary site.
Detailed description
Upon determination of eligibility, all patients will be randomly assigned to one of two treatment arms: * Paclitaxel + Carboplatin + Etoposide * Irinotecan + Gemcitabine Patients will be stratified by tumor location (liver/bone versus all others) and number of metastatic sites (one versus two or more). Patients with an objective response or stable disease after completion of chemotherapy will receive ZD1839 until disease progression. Patients who do not respond to chemotherapy may crossover to the other chemotherapy regimen and will receive ZD1839 if they have an objective response or stable disease. The study is not blinded so both the patient and the doctor will know which treatment has been assigned.
Interventions
DRUGEtoposide
50 mg alternating with 100 mg PO, days 1 and 10 in regimen A
DRUGGemcitabine
1000 mg/m2 IV, days 1 and 8, in regimen B
DRUGIrinotecan
1000 mg/m2 IV days 1 and 8 in regimen B
DRUGPaclitaxel
200 mg/m2 by 1-hour IV infusion, day 1, regimen A
DRUGCarboplatin
Area under the curve (AUC) 6.0 IV, day 1, regimen A
Sponsors
AstraZeneca
Pharmacia and Upjohn
Eli Lilly and Company
SCRI Development Innovations, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be included in this study, you must meet the following criteria: * Carcinoma of unknown primary site * Biopsy-proven metastatic carcinoma * Able to perform activities of daily living with minimal assistance * No previous treatment with any systemic therapy * Measurable or evaluable disease * Adequate bone marrow, liver and kidney function * Understand the nature of this study and give written informed consent
Exclusion criteria
You cannot participate in this study if any of the following apply to you: * Age \< 18 years * Uncontrolled brain metastases and meningeal involvement * Other uncontrolled malignancies * Women pregnant or lactating * Recent history of significant cardiovascular disease * Severe or uncontrolled systemic disease * Other significant clinical disorder * Clinically active interstitial lung disease Please note: There are additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 24 months | Length of time, in months, that patients were alive from their first date of protocol treatment until death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 12 months | Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paclitaxel/Carboplatin/Etoposide/Gefitinib Paclitaxel 200 mg/m2 by 1-hour IV infusion, day 1
Carboplatin area under the curve (AUC) 6.0 IV, day 1
Etoposide 50 mg alternating with 100 mg by mouth, days 1 and 10
Regimen A was repeated at a 21-day interval | 93 |
| Irinotecan/Gemcitabine/Gefitinib Irinotecan 100 mg/m2 IV, days 1 and 8
Gemcitabine 1000 mg/m2 IV, days 1 and 8
Regimen B was repeated at a 21-day interval | 105 |
| Total | 198 |
Baseline characteristics
| Characteristic | Paclitaxel/Carboplatin/Etoposide/Gefitinib | Irinotecan/Gemcitabine/Gefitinib | Total |
|---|---|---|---|
| Age Continuous | 61 years | 59 years | 60 years |
| Region of Enrollment United States | 93 participants | 105 participants | 198 participants |
| Sex: Female, Male Female | 49 Participants | 42 Participants | 91 Participants |
| Sex: Female, Male Male | 44 Participants | 63 Participants | 107 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 93 / 93 | 105 / 105 |
| serious Total, serious adverse events | 56 / 93 | 57 / 105 |
Outcome results
Primary
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Length of time, in months, that patients were alive from their first date of protocol treatment until death.
Time frame: 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel/Carboplatin/Etoposide/Gefitinib | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 7.4 months |
| Irinotecan/Gemcitabine/Gefitinib | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 8.5 months |
Secondary
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paclitaxel/Carboplatin/Etoposide/Gefitinib | Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 3.3 months |
| Irinotecan/Gemcitabine/Gefitinib | Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 5.3 months |