Trial Outcomes & Findings for GTI-2040 and Capecitabine in Treating Patients With Metastatic Breast Cancer (NCT NCT00068588)

Last Updated: 2014-10-31

Results Overview

1st 3 pts will be treated on arm 2. If 0/3 DLTs observed, the dose will be escalated to arm 3. If 1/3 DLTs onserved on arm 2, 3 more pts will be treated on arm 2. If no additional DLTs are observed on arm 2, the dose will be escalated to arm 3. If at most 1/6 DLTs observed on arm 3, arm 3 will be considered the MTD. If more than 1/6 DLTs observed on arm 3, the dose will be de-escalated to arm 2. If at most 1/6 DLTs observed on arm 2, arm 2 will be considered the MTD. If more than 1/6 pts on arm 2 experience a DLT, the dose will be de-escalated to arm 1. The remaining pts will be treated on arm 1 as the MTD, unless more than 1/6 DLTs, in which case the study will stop. DLT is defined as any grade III or IV non-hematologic toxicity (incl. diarrhea w\\ adequate antidiarrheal treatment \& hydration \& nausea/vomiting w\\ maximal antiemetic prophylaxis, as per protocol) or grade IV hematologic toxicity. DLT will be based on the 1st course of treatment according to the revised NCI CTC v 2.0

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

21 days

Results posted on

2014-10-31

Participant Flow

1st 3 pts treated on arm 2. If 0/3 DLTs, escalate to arm 3. If 1/3 DLTs on arm 2, 3 more pts on arm 2. If 1/6 DLTs on arm 2, escalate to arm 3.If at most 1/6 DLTs on arm 3, MTD declared. If more than 1/6 DLTs on arm 3, then de-escalated to arm 2. If at most 1/6 DLTs on arm 2, MTD declared. If more than 1/6 DLTs on arm 2, then de-escalate to arm 1.

Participant milestones

Participant milestones
Measure	Arm 2 Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 3 Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Overall Study STARTED	3	21
Overall Study COMPLETED	3	17
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1 Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 2 Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 3 Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Overall Study Adverse Event	0	0	2
Overall Study Withdrawal by Subject	0	0	1
Overall Study Poor KPS	0	0	1

Baseline Characteristics

GTI-2040 and Capecitabine in Treating Patients With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1 Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 2 n=3 Participants Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 3 n=21 Participants Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Total n=24 Participants Total of all reporting groups
Age, Continuous	—	63 years n=4 Participants	52 years n=27 Participants	53 years n=483 Participants
Gender Female	—	3 participants n=4 Participants	21 participants n=27 Participants	24 participants n=483 Participants
Gender Male	—	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants
Region of Enrollment United States	—	3 participants n=4 Participants	21 participants n=27 Participants	24 participants n=483 Participants

PRIMARY outcome

Timeframe: 21 days

Outcome measures

Outcome measures
Measure	Arm 1 Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 2 n=3 Participants Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 3 n=6 Participants Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Maximum Tolerated Dose Determined by Dose-limiting Toxicities	—	0 Patients experiencing DLT	0 Patients experiencing DLT

PRIMARY outcome

Timeframe: Up to 6 years

Population: Response Rate was only assessed at the determined MTD. Additional patients were accrued to determine treatment efficacy at the MTD.

Following the dose escalation step, additional patients will be accrued at the MTD and evaluated for disease response using RECIST v1.0 criteria. Patients with confirmed complete or partial response are considered to have responded favorably to treatment.The sample size and early stopping for futility was governed by a two stage Optimum design suggested by Simon. It was assumed that a true response rate less than 25% would not warrant further study of this agent. It was also assumed that a response rate of 45% would be considered promising. In the first stage (following the dose escalation step), 15 evaluable patients were treated. Four or fewer observed responses, would stop accrual, while 5 or more observed would continue accrual for an additional 12 patients during the second stage of the study. Ten or more responses out of 27 patients will be considered evidence warranting further study of the regimen providing toxicity and survival also appear favorable.

Outcome measures

Outcome measures
Measure	Arm 1 Capecitabine 800 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 2 Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 3 n=15 Participants Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Response Rate of a Combination of GTI-2040 and Capecitabine	—	—	20 percentage of patients responding

Adverse Events

Arm 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Arm 3

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

DCC Project Administrator

California Cancer Consortium

Phone: 626-256-4673

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm 2 n=3 participants at risk Capecitabine 1000 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,	Arm 3 n=21 participants at risk Capecitabine 1250 mg/m2 BID for 14 days on days 2-15 of each 21 day cycle +GTI-2040 civ infusion 185 mg/m2/day on days 1-15 of cycle 1 and days 1-14 of each subsequent cycle,
Gastrointestinal disorders Diarrhea	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	9.5% 2/21 • Number of events 2 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Catheter related infection	33.3% 1/3 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/21 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Infection NOS	33.3% 1/3 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	9.5% 2/21 • Number of events 2 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypophosphatemia	33.3% 1/3 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	9.5% 2/21 • Number of events 2 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Depressed level of consciousness	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 2 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Peripheral sensory neuropathy	33.3% 1/3 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/21 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urogenital disorder	0.00% 0/3 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	4.8% 1/21 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Skin disorder	33.3% 1/3 • Number of events 1 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/21 • Adverse event data was collected over a 5.5 year period in which patients were actively treated. There was one death six days after treatment stopped possibly related to treatment described as "somnolence/depressed level of consciousness". "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.