Trial Outcomes & Findings for Capecitabine, Carboplatin and Weekly Paclitaxel for Patients With Solid Tumors and Adenocarcinoma of Unknown Primary (NCT NCT00201734)

NCT ID: NCT00201734

Last Updated: 2016-09-23

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

57 participants

Primary outcome timeframe

Every 3 weeks, for up to 24 weeks

Results posted on

2016-09-23

Participant Flow

Patients were enrolled to the trial between July 2005 and November 2007

Participant milestones

Participant milestones
Measure	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.	Phase II Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
Overall Study STARTED	32	25
Overall Study Patients Not Evaluable	3	0
Overall Study COMPLETED	29	25
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Capecitabine, Carboplatin and Weekly Paclitaxel for Patients With Solid Tumors and Adenocarcinoma of Unknown Primary

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I n=32 Participants 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 n=25 Participants Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.	Total n=57 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	28 Participants n=5 Participants	21 Participants n=7 Participants	49 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	13 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	24 Participants n=7 Participants	53 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	32 patients n=5 Participants	25 patients n=7 Participants	57 patients n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase I Patients n=29 Participants 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 Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
Maximum Tolerated Dose in Phase I Portion of Study	750 mg/m2	—

PRIMARY outcome

Timeframe: Every 3 weeks, for up to 24 weeks

Population: The Phase II study was prematurely terminated at 25 patients due to cessation of funding

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

Outcome measures

Outcome measures
Measure	Phase I Patients n=29 Participants 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 n=25 Participants Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
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 Interval 8.0 to 40.0	32 percent of patients Interval 15.0 to 54.0

SECONDARY outcome

Timeframe: Every 3 weeks, for up to 24 weeks

Population: Three patients enrolled on Phase I portion of trial were not evaluable for toxicity.

The common clinically significant grade 3 and 4 toxicities graded using the National Cancer Institutes Common Toxicity Criteria version 3.0

Outcome measures

Outcome measures
Measure	Phase I Patients n=29 Participants 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 n=25 Participants Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
Phase I: To Determine Side Effects Neutropenia	86 percent of patients	72 percent of patients
Phase I: To Determine Side Effects Thrombocytopenia	72 percent of patients	72 percent of patients
Phase I: To Determine Side Effects Fatigue	76 percent of patients	84 percent of patients

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Phase I Patients 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 n=25 Participants Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
Progression-Free Survival at 6 Months for Patients	—	38 percent of patients Interval 22.0 to 54.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase I Patients 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 n=25 Participants Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
One Year Survival for Patients	—	44 percent of patients Interval 24.0 to 62.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Phase I Patients 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 n=25 Participants Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
Time to Tumor Progression for Patients	—	5.5 months Interval 2.8 to 10.8

Adverse Events

Phase I

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Phase II

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Tanios Bekaii-Saab, MD

The Ohio State University Comprehensive Cancer Center

Phone: 614-293-9863

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I n=29 participants at risk 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 n=25 participants at risk Phase II trial combination at the recommended doses from the Phase I portion in patients with adenocarcinoma of unknown primary site.
Blood and lymphatic system disorders Anemia	82.8% 24/29 • Number of events 24 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	88.0% 22/25 • Number of events 22 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Blood and lymphatic system disorders Leukopenia	96.6% 28/29 • Number of events 28 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	40.0% 10/25 • Number of events 10 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Blood and lymphatic system disorders Lymphopenia	65.5% 19/29 • Number of events 19 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	48.0% 12/25 • Number of events 12 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Blood and lymphatic system disorders Neutropenia	86.2% 25/29 • Number of events 25 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	72.0% 18/25 • Number of events 18 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Blood and lymphatic system disorders Thrombocytopenia	72.4% 21/29 • Number of events 21 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	72.0% 18/25 • Number of events 18 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Gastrointestinal disorders Anorexia	34.5% 10/29 • Number of events 10 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	28.0% 7/25 • Number of events 7 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Gastrointestinal disorders Diarrhea	62.1% 18/29 • Number of events 18 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	72.0% 18/25 • Number of events 18 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
General disorders Fatigue	75.9% 22/29 • Number of events 22 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	84.0% 21/25 • Number of events 21 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
General disorders Fever without Neutropenia	27.6% 8/29 • Number of events 8 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	12.0% 3/25 • Number of events 3 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Skin and subcutaneous tissue disorders Hand Foot Syndrome	44.8% 13/29 • Number of events 13 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	20.0% 5/25 • Number of events 5 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Gastrointestinal disorders Mucositis	27.6% 8/29 • Number of events 8 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	44.0% 11/25 • Number of events 11 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Gastrointestinal disorders Nausea	79.3% 23/29 • Number of events 23 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	72.0% 18/25 • Number of events 18 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Gastrointestinal disorders Vomiting	37.9% 11/29 • Number of events 11 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	56.0% 14/25 • Number of events 14 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Nervous system disorders Neuropathy	62.1% 18/29 • Number of events 18 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	60.0% 15/25 • Number of events 15 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.
Skin and subcutaneous tissue disorders Rash	20.7% 6/29 • Number of events 6 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.	24.0% 6/25 • Number of events 6 Adverse Events were graded using the National Cancer Institute Common Toxicity Criteria version 3.0.