Adenocarcinoma, Tumors, Unknown Primary Tumors
Conditions
Keywords
Adenocarcinoma
Brief summary
This study will determine the maximum tolerated dose of the triplet combination of capecitabine that can be administered in combination with weekly paclitaxel and every four weeks with carboplatin.
Detailed description
Rationale: The combination of the chemotherapy drugs paclitaxel and carboplatin is one of the most common combination regimens used in clinical practice for cancer. These agents are used for a variety of cancers. The current study builds on previous research about treatment schedules for administering these agents to reduce toxicity and optimize efficacy. The phase I and II portions of the current study combine paclitaxel and carboplatin with capecitabine in patients. Researchers are seeking to identify the highest dose of capecitabine and paclitaxel in combination with carboplatin for this patient population, as well as to gather information about preliminary efficacy. Purpose: The phase I portion of this study will evaluate the maximum tolerated dose of capecitabine and paclitaxel in combination with carboplatin for patients. The phase II portion of this study will assess the objective response rate in patients using the same treatment combination. Toxicities will be closely measured in both phases of the study. Treatment: Patients in this study will be given capecitabine, carboplatin, and paclitaxel. Capecitabine will be given through oral pills. Carboplatin and paclitaxel will be given through intravenous infusions. Treatment drugs will be given on a four-week cycle. Carboplatin will be administered on day 1, paclitaxel weekly for the first 3 weeks, and capecitabine twice daily on days 8 through 21 of each cycle. No treatments will be given during the fourth week of each treatment cycle. During the phase I portion of the study, patients may receive different doses of capecitabine and paclitaxel since the purpose is to identify the maximum tolerated dose of each drug in combination with carboplatin. Once the maximum tolerated dose of these agents is identified during phase I, the phase II portion of the study will begin. Treatments will be discontinued due to disease growth or unacceptable side effects. Several tests and exams will be given throughout the study to closely monitor patients.
Interventions
DRUGCapecitabine
Level 1: 500 mg/m2 orally twice daily Days 8 - 21 of each cycle. Level 2: 750 mg/m2 orally twice daily Days 8 - 21 of each cycle. Level 3 - 5: 1000mg/m2 orally twice daily Days 8 - 21 of each cycle.
DRUGCarboplatin
Levels 1-5: AUC of 6 every 4 weeks.
DRUGPaclitaxel
Level 1-3: 60 mg/m2/week. Level 4: 80 mg/m2/week. Level 5: 100 mg/m2/week.
Sponsors
Roche Pharma AG
Ohio State University Comprehensive Cancer Center
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
for Phase I: * All advanced solid malignancies * Any prior chemotherapy permitted * Performance Status 0-2 Inclusion Criteria for Phase II: * Adenocarcinoma of unknown primary * No prior chemo permitted * Performance Status 0-2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose in Phase I Portion of Study | Every 3 weeks, for up to 24 weeks | Determine the maximum tolerated dose of the triplet combination of capecitabine that can be administered in combination with weekly paclitaxel and every four weeks carboplatin. |
| Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design. | Every 3 weeks, for up to 24 weeks | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: To Determine Side Effects | Every 3 weeks, for up to 24 weeks | The common clinically significant grade 3 and 4 toxicities graded using the National Cancer Institutes Common Toxicity Criteria version 3.0 |
| Progression-Free Survival at 6 Months for Patients | up to 6 years | For patients enrolled on the Phase II portion of the trial Progression Free Survival (PFS) was measured from the percentage of patients that were still alive, without evidence of disease progression for 6 months following the initiation of treatment. 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 |
| One Year Survival for Patients | Up to 1 year | For patients enrolled on the Phase II portion of the trial the One-year survival was measured as the percentage of patients alive 1 year after their treatment in the trial. |
| Time to Tumor Progression for Patients | Up to 6 years | For patients enrolled on the Phase II portion of the trial the time to progression was measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression. |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled to the trial between July 2005 and November 2007
Participants by arm
| Arm | Count |
|---|---|
| Phase I Cycles will be of 4-week duration. Carboplatin was administered on day 1 intravenously for 3 weeks (days 1, 8, 15) and paclitaxel weekly intravenously for 3 weeks on days 1, 8 and 15. Capecitabine was given orally twice daily days 18-21 followed by 1 week rest. | 32 |
| Phase II Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. | 25 |
| Total | 57 |
Baseline characteristics
| Characteristic | Phase I | Phase II | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 21 Participants | 49 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 29 Participants | 24 Participants | 53 Participants |
| Region of Enrollment United States | 32 patients | 25 patients | 57 patients |
| Sex: Female, Male Female | 6 Participants | 12 Participants | 18 Participants |
| Sex: Female, Male Male | 26 Participants | 13 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 29 | 25 / 25 |
| serious Total, serious adverse events | 0 / 29 | 0 / 25 |
Outcome results
Primary
Maximum Tolerated Dose in Phase I Portion of Study
Determine the maximum tolerated dose of the triplet combination of capecitabine that can be administered in combination with weekly paclitaxel and every four weeks carboplatin.
Time frame: Every 3 weeks, for up to 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Patients | Maximum Tolerated Dose in Phase I Portion of Study | 750 mg/m2 |
Primary
Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Every 3 weeks, for up to 24 weeks
Population: The Phase II study was prematurely terminated at 25 patients due to cessation of funding
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Patients | Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design. | 21 percent of patients |
| Phase II | Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design. | 32 percent of patients |
Secondary
One Year Survival for Patients
For patients enrolled on the Phase II portion of the trial the One-year survival was measured as the percentage of patients alive 1 year after their treatment in the trial.
Time frame: Up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II | One Year Survival for Patients | 44 percent of patients |
Secondary
Phase I: To Determine Side Effects
The common clinically significant grade 3 and 4 toxicities graded using the National Cancer Institutes Common Toxicity Criteria version 3.0
Time frame: Every 3 weeks, for up to 24 weeks
Population: Three patients enrolled on Phase I portion of trial were not evaluable for toxicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I Patients | Phase I: To Determine Side Effects | Neutropenia | 86 percent of patients |
| Phase I Patients | Phase I: To Determine Side Effects | Thrombocytopenia | 72 percent of patients |
| Phase I Patients | Phase I: To Determine Side Effects | Fatigue | 76 percent of patients |
| Phase II | Phase I: To Determine Side Effects | Fatigue | 84 percent of patients |
| Phase II | Phase I: To Determine Side Effects | Neutropenia | 72 percent of patients |
| Phase II | Phase I: To Determine Side Effects | Thrombocytopenia | 72 percent of patients |
Secondary
Progression-Free Survival at 6 Months for Patients
For patients enrolled on the Phase II portion of the trial Progression Free Survival (PFS) was measured from the percentage of patients that were still alive, without evidence of disease progression for 6 months following the initiation of treatment. 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: up to 6 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase II | Progression-Free Survival at 6 Months for Patients | 38 percent of patients |
Secondary
Time to Tumor Progression for Patients
For patients enrolled on the Phase II portion of the trial the time to progression was measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression.
Time frame: Up to 6 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase II | Time to Tumor Progression for Patients | 5.5 months |