Trial Outcomes & Findings for Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma (NCT NCT00506779)

Last Updated: 2020-11-18

Results Overview

Maximum Tolerated Dose (MTD) of Oral Imatinib Mesylate in Combination with Fixed Dose Paclitaxel where MTD of Imatinib Mesylate (mg/m\^2 daily) to be determined with conventional 3+3 design, MTD is highest dose level in which 6 participants treated with at most 2 experiencing dose limiting toxicity (DLT). Study utilizes Common Terminology for Adverse Events Criteria (CTCAE) version 3.0 for adverse event reporting. Following cohorts of 3 at lower dose levels until 1 of 3 patients experiences DLT; if 1 of 3 patients experiences DLT at dose level, enter 3 additional patients at dose level, if only 1 of 6 patients experiences DLT at dose level, proceed to next higher dose level with cohort of 3; If 2 of 3 or 3 of 6 patients experience DLT, MTD has exceeded. Once DLT exceeded, treat another 3 patients at previous dose if there were only 3 patients treated at that dose level. MTD is highest dose level in which treated 6 patients with at most 2 experiencing the DLT.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Evaluated at 3 weeks (one cycle)

Results posted on

2020-11-18

Participant Flow

Recruitment Period: December 29, 2003 to October 27, 2009. Recruitment was done at The University of Texas MD Anderson Cancer Center.

The study was terminated early due to poor enrollment .

Participant milestones

Participant milestones
Measure	Phase I: Imatinib Mesylate 400 mg Cohort One = Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec). Phase I Maximum Tolerated Dose (MTD) to be determined from escalating doses in subsequent cohorts: 400 (this arm, Cohort One), 500 (Cohort Two) or 600 mg (Cohort Three) orally daily.	Phase I: Imatinib Mesylate 500 mg Cohort Two = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily	Phase I: Imatinib Mesylate 600 mg Cohort Three = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily	Phase II: Imatinib Mesylate MTD 500 mg Phase II, Cohort 4 = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally daily
Overall Study STARTED	4	6	2	5
Overall Study COMPLETED	3	5	0	4
Overall Study NOT COMPLETED	1	1	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: Imatinib Mesylate 400 mg Cohort One = Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec). Phase I Maximum Tolerated Dose (MTD) to be determined from escalating doses in subsequent cohorts: 400 (this arm, Cohort One), 500 (Cohort Two) or 600 mg (Cohort Three) orally daily.	Phase I: Imatinib Mesylate 500 mg Cohort Two = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily	Phase I: Imatinib Mesylate 600 mg Cohort Three = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily	Phase II: Imatinib Mesylate MTD 500 mg Phase II, Cohort 4 = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally daily
Overall Study Withdrawal by Subject	1	0	1	0
Overall Study Adverse Event	0	1	1	1

Baseline Characteristics

Gleevec/Taxol for Patients With Uterine Papillary Serous Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Paclitaxel + Imatinib Mesylate n=12 Participants Phase I = Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec) 400, 500 or 600 mg orally daily	Phase II: Paclitaxel + Imatinib Mesylate MTD 500 mg n=5 Participants Phase II = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally daily	Total n=17 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	70 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	4 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	10 Participants n=5 Participants	4 Participants n=7 Participants	14 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	5 participants n=7 Participants	17 participants n=5 Participants

PRIMARY outcome

Timeframe: Evaluated at 3 weeks (one cycle)

Population: One participant of 12 registered withdrew prior to receiving treatment.

Outcome measures

Outcome measures
Measure	Imatinib Mesylate 400 mg n=4 Participants Cohort One = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 400 mg orally daily	Imatinib Mesylate 500 mg n=6 Participants Cohort Two = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily	Imatinib Mesylate 600 mg n=2 Participants Cohort Three = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)	0 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: 6 weeks to 18 weeks; Best response achieved since study entry where measurable disease defined as => 1 lesion accurately measured in at least 1 dimension (longest dimension to be recorded)

Complete Response (CR): Disappearance lesions, no evidence new lesions documented by 2 disease assessments\> 4 weeks apart. Partial Response (PR):\>30% decrease in sum longest dimensions (LD) all target measurable lesions reference baseline sum of LD; No progression non-target lesions \& no new lesions; Documentation by 2 disease assessments \>4 weeks apart; Progressive Disease (PD) (ANY of following): \>20% increase in sum LD of target lesions reference smallest sum LD or appearance of new lesions within 8 weeks of study entry; Unequivocal progression on existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin, within 8 weeks of study entry also considered increasing disease. Death due to disease without prior objective documentation of progression; Global deterioration in health attributable to disease requiring change in therapy without objective evidence of progression. Stable disease: Any condition not meeting above criteria.

Outcome measures

Outcome measures
Measure	Imatinib Mesylate 400 mg n=8 Participants Cohort One = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 400 mg orally daily	Imatinib Mesylate 500 mg n=8 Participants Cohort Two = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily	Imatinib Mesylate 600 mg Cohort Three = Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily
Number of Participants With Complete Response	1 participants	7 participants	—

SECONDARY outcome

Timeframe: Evaluation at at 6 weeks, tumor restaging continued up to 6 cycles (18 weeks) or until disease progression, whichever comes first

Population: Due to poor enrollment, the study was terminated early and no data collected for the Time to tumor progression outcome measure.

Efficacy of Gleevec and Taxol in Participants defined by tumor progression for participants with measurable disease or recurrent non-measurable disease. Time to tumor progression defined as the time from date of initial treatment to first objective documentation of disease progression. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). After two cycles (6 weeks), participants will undergo clinical and radiographic (participants with measurable disease) tumor restaging or confirmation recurrent non-measurable disease. Evaluation of tumor response (for participants who already have the disease) determined by CT scan or MRI and chest x-ray (participants with chest disease).

Outcome measures

Outcome data not reported

Adverse Events

Phase I: Imatinib Mesylate 400mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Phase II: Imatinib Mesylate 500 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase 1: Imatinib Mesylate 600 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Phase II: Imatinib Mesylate MTD 500 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

David Gershenson, MD

University of Texas (UT) MD Anderson Cancer Center

Phone: 713-745-2565

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I: Imatinib Mesylate 400mg n=4 participants at risk Cohort One = Paclitaxel (Taxol) 175 mg/m\^2 intravenous (IV) every 21 days + Imatinib Mesylate (Gleevec). Phase I Maximum Tolerated Dose (MTD) to be determined from escalating doses in subsequent cohorts: 400 (this arm, Cohort One), 500 (Cohort Two) or 600 mg (Cohort Three) orally daily.	Phase II: Imatinib Mesylate 500 mg n=6 participants at risk Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 500 mg orally daily	Phase 1: Imatinib Mesylate 600 mg n=2 participants at risk Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate 600 mg orally daily	Phase II: Imatinib Mesylate MTD 500 mg n=5 participants at risk Paclitaxel 175 mg/m\^2 IV every 21 days + Imatinib Mesylate at MTD 500 mg orally
Blood and lymphatic system disorders Fever w/o Neutropenia	50.0% 2/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
General disorders Fatigue	100.0% 4/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 6/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 2/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	60.0% 3/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Nervous system disorders Neuropathy	75.0% 3/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 3/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 2/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	60.0% 3/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Metabolism and nutrition disorders Hypokalemia	50.0% 2/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Musculoskeletal and connective tissue disorders Pain - back	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Nervous system disorders Headache	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	33.3% 2/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	40.0% 2/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Musculoskeletal and connective tissue disorders Pain - Joint	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 2/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	40.0% 2/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Musculoskeletal and connective tissue disorders Pain - Muscle	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	40.0% 2/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Blood and lymphatic system disorders Neutrophils	100.0% 4/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 6/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	80.0% 4/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Blood and lymphatic system disorders Hemoglobin	50.0% 2/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 6/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	80.0% 4/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Blood and lymphatic system disorders Platelets	0.00% 0/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Skin and subcutaneous tissue disorders Alopecia	75.0% 3/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 6/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Gastrointestinal disorders Nausea	100.0% 4/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	83.3% 5/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	100.0% 2/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	60.0% 3/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Gastrointestinal disorders Vomiting	100.0% 4/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	66.7% 4/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Metabolism and nutrition disorders Anorexia	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Gastrointestinal disorders Pain - abdomen	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Musculoskeletal and connective tissue disorders Pain - bone	0.00% 0/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Skin and subcutaneous tissue disorders Rash - desquamation	0.00% 0/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 3/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Nervous system disorders Mood alteration - anxiety	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Eye disorders Tinnitus	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Skin and subcutaneous tissue disorders Edema - facial	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Skin and subcutaneous tissue disorders Flushing	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
General disorders Pain - pleura	25.0% 1/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	50.0% 1/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Gastrointestinal disorders Heartburn	0.00% 0/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Metabolism and nutrition disorders SGOT - elevated	0.00% 0/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).
Metabolism and nutrition disorders SGPT - elevated	0.00% 0/4 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	16.7% 1/6 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	0.00% 0/2 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).	20.0% 1/5 • Adverse Event collection with each 3 week cycle, up to 6 cycles (18 weeks).