Neoplasm, Unknown Primary
Conditions
Keywords
Neoplasm, Unknown Primary
Brief summary
We will evaluate the feasibility, toxicity, and effectiveness of combination chemotherapy (paclitaxel/carboplatin)plus combination targeted therapy (bevacizumab/erlotinib)in the first line treatment of patients with carcinoma of unknown primary site. There is limited experience with either bevacizumab or erlotinib in the treatment of cancers of unknown site but given the heterogeneous nature of the tumor, it is likely that inhibition of angiogenesis pathways and/or the EGFR pathway are effective strategies in at least a proportion.
Detailed description
All eligible patients will receive: * Bevacizumab 15mg/kg IV infusion,Day 1 * Paclitaxel 175mg/m2, 1-3 hour IV infusion,Day 1 * Carboplatin AUC 6.0 IV Day 1 * Erlotinib 150 mg by mouth daily The regimen will be repeated every 21 days for a total of 4 courses. Patients will be initially evaluated for response after completing 2 courses (6 weeks) of treatment. Patients with an objective tumor response or stable disease will continue treatment for another 2 courses. Patients will be re-evaluated after 4 courses and those with objective tumor response or stable disease will stop chemotherapy with paclitaxel/carboplatin and continue treatment with bevacizumab/erlotinib until tumor progression is documented for a maximum of 12 months. During treatment with bevacizumab/erlotinib response will be evaluated every 12 weeks.
Interventions
DRUGpaclitaxel
Paclitaxel 175mg/m2, 1-3 hour IV infusion,Day 1
DRUGcarboplatin
Carboplatin AUC 6.0 IV Day 1
DRUGbevacizumab
Bevacizumab 15mg/kg IV infusion,Day 1
DRUGerlotinib
Erlotinib 150 mg by mouth daily
Sponsors
Genentech, Inc.
SCRI Development Innovations, LLC
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
* Biopsy proven metastatic carcinoma with the following light microscopic histologies: adenocarcinoma, poorly differentiated carcinoma(must have immunoperoxidase stains to rule out lymphoma, neuroendocrine carcinoma),or poorly differentiated squamous carcinoma. * ECOG performance status 0-1 * No previous treatment with any systemic therapy * Adequate kidney, liver and bone marrow function * Be able to understand the nature of the study and give written informed consent
Exclusion criteria
* The following specific syndromes: * Neuroendocrine carcinoma * Women with adenocarcinoma isolated to axillary lymph nodes * Women with adenocarcinoma isolated to peritoneal involvement * Carcinoma involving only one site with resectable tumors at that site * Squamous carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes * Uncontrolled brain metastases and all patients with meningeal involvement * Women pregnant or lactating * Clinically significant cardiovascular disease * History of myocardial infarction or stroke within 6 months * Clinical history of hemoptysis or hematemesis * Patients with PEG tubes or G-tubes * Proteinuria * History of bleeding diathesis or coagulopathy Please note: There are additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 18 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 18 months | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab/Paclitaxel/Carboplatin/Erlotinib Bevacizumab 15mg/kg IV infusion,Day 1 Paclitaxel 175mg/m2, 1-3 hour IV infusion,Day 1 Carboplatin AUC 6.0 IV Day 1 Erlotinib 150 mg by mouth daily | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Bevacizumab/Paclitaxel/Carboplatin/Erlotinib |
|---|---|
| Age Continuous | 50 years |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 60 / 60 |
| serious Total, serious adverse events | 29 / 60 |
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
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Paclitaxel/Carboplatin/Erlotinib | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 12.6 months |
Secondary
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Paclitaxel/Carboplatin/Erlotinib | Progression-free Survival | 8 months |