Capecitabine, Carboplatin and Weekly Paclitaxel for Patients With Solid Tumors and Adenocarcinoma of Unknown Primary
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm I Patients receive paclitaxel IV over 60 minutes on days 1, 8, and 15, carboplatin IV over 1-2 hours on day 1, and capecitabine PO BID on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Drug: Capecitabine
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.
Other Names:
Drug: Carboplatin
Levels 1-5: AUC of 6 every 4 weeks.
Other Names:
Drug: Paclitaxel
Level 1-3: 60 mg/m2/week. Level 4: 80 mg/m2/week. Level 5: 100 mg/m2/week.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- Ohio State University Comprehensive Cancer Center
- Roche Pharma AG
Investigators
- Principal Investigator: Tony Bekaii-Saab, Ohio State University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- OSU-0317
- NCI-2011-03593
Study Results
Participant Flow
| Recruitment Details | Patients were enrolled to the trial between July 2005 and November 2007 |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase I | Phase II |
|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. |
| Period Title: Overall Study | ||
| STARTED | 32 | 25 |
| Patients Not Evaluable | 3 | 0 |
| COMPLETED | 29 | 25 |
| NOT COMPLETED | 3 | 0 |
Baseline Characteristics
| Arm/Group Title | Phase I | Phase II | Total |
|---|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. | Total of all reporting groups |
| Overall Participants | 32 | 25 | 57 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
28
87.5%
|
21
84%
|
49
86%
|
| >=65 years |
4
12.5%
|
4
16%
|
8
14%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
18.8%
|
12
48%
|
18
31.6%
|
| Male |
26
81.3%
|
13
52%
|
39
68.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
6.3%
|
1
4%
|
3
5.3%
|
| White |
29
90.6%
|
24
96%
|
53
93%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
3.1%
|
0
0%
|
1
1.8%
|
| Region of Enrollment (patients) [Number] | |||
| United States |
32
|
25
|
57
|
Outcome Measures
| Title | Maximum Tolerated Dose in Phase I Portion of Study |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase I Patients |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 29 |
| Number [mg/m2] |
750
|
| Title | 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. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Phase II study was prematurely terminated at 25 patients due to cessation of funding |
| Arm/Group Title | Phase I | Phase II |
|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. |
| Measure Participants | 29 | 25 |
| Number (95% Confidence Interval) [percent of patients] |
21
|
32
|
| Title | Phase I: To Determine Side Effects |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Three patients enrolled on Phase I portion of trial were not evaluable for toxicity. |
| Arm/Group Title | Phase I | Phase II |
|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. |
| Measure Participants | 29 | 25 |
| Neutropenia |
86
|
72
|
| Thrombocytopenia |
72
|
72
|
| Fatigue |
76
|
84
|
| Title | Progression-Free Survival at 6 Months for Patients |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase I | Phase II |
|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. |
| Measure Participants | 0 | 25 |
| Number (95% Confidence Interval) [percent of patients] |
38
|
| Title | One Year Survival for Patients |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase I | Phase II |
|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. |
| Measure Participants | 0 | 25 |
| Number (95% Confidence Interval) [percent of patients] |
44
|
| Title | Time to Tumor Progression for Patients |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Phase I | Phase II |
|---|---|---|
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. |
| Measure Participants | 0 | 25 |
| Median (95% Confidence Interval) [months] |
5.5
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0. | |||
| Arm/Group Title | Phase I | Phase II | ||
| Arm/Group Description | 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. | Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site. | ||
All Cause Mortality |
||||
| Phase I | Phase II | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Phase I | Phase II | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/29 (0%) | 0/25 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Phase I | Phase II | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 29/29 (100%) | 25/25 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 24/29 (82.8%) | 24 | 22/25 (88%) | 22 |
| Leukopenia | 28/29 (96.6%) | 28 | 10/25 (40%) | 10 |
| Lymphopenia | 19/29 (65.5%) | 19 | 12/25 (48%) | 12 |
| Neutropenia | 25/29 (86.2%) | 25 | 18/25 (72%) | 18 |
| Thrombocytopenia | 21/29 (72.4%) | 21 | 18/25 (72%) | 18 |
| Gastrointestinal disorders | ||||
| Anorexia | 10/29 (34.5%) | 10 | 7/25 (28%) | 7 |
| Diarrhea | 18/29 (62.1%) | 18 | 18/25 (72%) | 18 |
| Mucositis | 8/29 (27.6%) | 8 | 11/25 (44%) | 11 |
| Nausea | 23/29 (79.3%) | 23 | 18/25 (72%) | 18 |
| Vomiting | 11/29 (37.9%) | 11 | 14/25 (56%) | 14 |
| General disorders | ||||
| Fatigue | 22/29 (75.9%) | 22 | 21/25 (84%) | 21 |
| Fever without Neutropenia | 8/29 (27.6%) | 8 | 3/25 (12%) | 3 |
| Nervous system disorders | ||||
| Neuropathy | 18/29 (62.1%) | 18 | 15/25 (60%) | 15 |
| Skin and subcutaneous tissue disorders | ||||
| Hand Foot Syndrome | 13/29 (44.8%) | 13 | 5/25 (20%) | 5 |
| Rash | 6/29 (20.7%) | 6 | 6/25 (24%) | 6 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Tanios Bekaii-Saab, MD |
|---|---|
| Organization | The Ohio State University Comprehensive Cancer Center |
| Phone | 614-293-9863 |
| tanios.bekaii-saab@osumc.edu |
- OSU-0317
- NCI-2011-03593