Trial Outcomes & Findings for Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer (NCT NCT00616967)
NCT ID: NCT00616967
Last Updated: 2025-02-27
Results Overview
The primary end point was pCR, defined as no viable invasive cancer in breast and axilla. All other cases were defined as non-pCR. The pCR rate was determined in each arm separately by performing an intent-to-treat (ITT) analysis of all randomized patients. Patients with unknown pCR status were considered non-responders. Computation of associated 90% confidence intervals did not account for the sequential design.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
68 participants
Primary outcome timeframe
Time of breast cancer surgery
Results posted on
2025-02-27
Participant Flow
Participant milestones
| Measure |
Run-in Phase (Arm 0)
Phase 0 - To confirm safety and dosing prior to moving to randomized phase 2 portion (Arms 1 and 2).
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV paclitaxel albumin-stabilized nanoparticle formulation: Given IV vorinostat: Given orally
|
Placebo (Arm I)
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Vorinostat (Arm II)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
31
|
31
|
|
Overall Study
COMPLETED
|
6
|
31
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Run-in Phase (Arm 0)
Phase 0 - To confirm safety and dosing prior to moving to randomized phase 2 portion (Arms 1 and 2).
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV paclitaxel albumin-stabilized nanoparticle formulation: Given IV vorinostat: Given orally
|
Placebo (Arm I)
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Vorinostat (Arm II)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer
Baseline characteristics by cohort
| Measure |
Placebo (Arm 1)
n=31 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Vorinostat (Arm 2)
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48 years
n=5 Participants
|
48 years
n=7 Participants
|
48 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
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
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
43 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
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
31 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
|
ECOG Performance Status
ECOG 0
|
30 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
ECOG Performance Status
ECOG 1
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Tumor Size
|
5 centimeters
n=5 Participants
|
4 centimeters
n=7 Participants
|
4 centimeters
n=5 Participants
|
|
Nodal Status
Negative
|
10 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Nodal Status
Positive
|
21 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Tumor Grade
Grade 2
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Tumor Grade
Grade 3
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Receptor Status
ER-/PR-
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Receptor Status
ER+/PR+
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Receptor Status
ER+/PR-
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Receptor Status
ER-/PR+
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time of breast cancer surgeryPopulation: The information for the primary populations for analysis are included (Placebo and Vorinostat arms). Data for this outcome measure was not collected from the initial "run-in phase" of 6 participants.
The primary end point was pCR, defined as no viable invasive cancer in breast and axilla. All other cases were defined as non-pCR. The pCR rate was determined in each arm separately by performing an intent-to-treat (ITT) analysis of all randomized patients. Patients with unknown pCR status were considered non-responders. Computation of associated 90% confidence intervals did not account for the sequential design.
Outcome measures
| Measure |
Arm I
n=31 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Pathological Complete Response (pCR) Rate
|
9 Participants
|
8 Participants
|
—
|
SECONDARY outcome
Timeframe: up to 30 days post-treatmentNumber of participants who experience adverse events as defined by NCI CTCAE version 3.0
Outcome measures
| Measure |
Arm I
n=6 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Safety as Measured by Number of Participants Who Experience Adverse Events
|
6 Participants
|
31 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: 12 weekscCR in the breast on physical is defined as the absence of any palpable abnormality on breast exam Iie: no skin or breast thickening, mass or associated skin or nipple changes)
Outcome measures
| Measure |
Arm I
n=31 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Number of Participants With Clinical Complete Response (cCR)
|
16 Participants
|
15 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline and day 15Population: 16/17 "Responders" (from Outcome 1) had PET data evaluable for analysis; 43/45 "non-responders" (from Outcome 1) had PET data evaluable for analysis. Reasons for PET data not evaluable included technically invalid 18F-FDG PET data (2 participants) and no available Day 15 18F-FDG PET data (1 participant).
Change in standard uptake value (SULmax) as measured by percentage reduction of SULmax. The standard uptake value used for the PET analysis was SULmax, which is the standard uptake value normalized for lean body mass.
Outcome measures
| Measure |
Arm I
n=16 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=43 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Change in Standard Uptake Value (SULmax) From Baseline to Day 15 on FDG-PET
|
63 percentage reduction in SULmax
Interval 4.4 to 85.3
|
32.9 percentage reduction in SULmax
Interval -84.2 to 77.1
|
—
|
SECONDARY outcome
Timeframe: Change from baseline to Cycle 1-Day 15Population: Only 8/17 and 36/45 specimens were evaluable for Ki-67 at both baseline and Day 15. Nonevaluable samples had no tumor cells present or Ki-67 unavailable at either or both time points.
Outcome measures
| Measure |
Arm I
n=8 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=36 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Absolute Change From Baseline in Ki-67
|
7.0 percent change in Ki-67
Standard Deviation 15.8
|
12.0 percent change in Ki-67
Standard Deviation 22.7
|
—
|
SECONDARY outcome
Timeframe: Change from baseline to Day 15Population: Methylation data was only evaluable in participants with both baseline and D15 tissue (48/62) and serum (58/62) specimens.
Change of CMI from baseline to Day 15 (D15), defined as log(D15 CMI + 1/baseline CMI + 1). The CMI was calculated as a sum of all gene-specific methylation indexes within a panel of 10 genes which included: HIST1H3C, AKR1B1, GPX7, HOXB4, TMEFF2, RASGRF2, COL6A2, ARHGEF7, TM6SF1, and RASSF1A.
Outcome measures
| Measure |
Arm I
n=62 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Change in Cumulative Methylation Index (CMI)
Tissue CMI change from baseline
|
14 CMI
Interval -310.0 to 69.0
|
—
|
—
|
|
Change in Cumulative Methylation Index (CMI)
Serum CMI change from baseline
|
0 CMI
Interval -120.0 to 29.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 15Population: Methylation data was only evaluable in 11/17 and 39/45 participants.
Outcome measures
| Measure |
Arm I
n=11 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=39 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Cumulative Methylation Index (CMI) at Day 15
|
10 CMI
Interval 1.0 to 40.0
|
44 CMI
Interval 0.0 to 163.0
|
—
|
SECONDARY outcome
Timeframe: Up to 12 weeksOutcome measures
| Measure |
Arm I
n=6 Participants
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
Vorinostat (Arm 2)
n=31 Participants
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Number of Participants Who Experience Death During Treatment
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to death of last participant (duration unknown)Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to death of last participant (duration unknown)Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to death of last participant (duration unknown)Outcome measures
Outcome data not reported
POST_HOC outcome
Timeframe: Time of breast cancer surgeryOutcome measures
Outcome data not reported
Adverse Events
Run-in Phase (Arm 0)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Arm I
Serious events: 3 serious events
Other events: 31 other events
Deaths: 0 deaths
Arm II
Serious events: 1 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Run-in Phase (Arm 0)
n=6 participants at risk
Phase 0 - To confirm safety and dosing prior to moving to randomized phase 2 portion (Arms 1 and 2).
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
Events summarized in this arm are those that met 5% reporting threshold in Arms I and II.
|
Arm I
n=31 participants at risk
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=31 participants at risk
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
0.00%
0/31 • 30 days following the 12 weeks of treatment
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
6.5%
2/31 • Number of events 2 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
Other adverse events
| Measure |
Run-in Phase (Arm 0)
n=6 participants at risk
Phase 0 - To confirm safety and dosing prior to moving to randomized phase 2 portion (Arms 1 and 2).
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
Events summarized in this arm are those that met 5% reporting threshold in Arms I and II.
|
Arm I
n=31 participants at risk
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
placebo: Given orally
|
Arm II
n=31 participants at risk
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
carboplatin: Given IV
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
vorinostat: Given orally
|
|---|---|---|---|
|
Immune system disorders
Allergic reaction
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
32.3%
10/31 • Number of events 10 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
|
Blood and lymphatic system disorders
Amemia (hemoglobin)
|
50.0%
3/6 • Number of events 3 • 30 days following the 12 weeks of treatment
|
29.0%
9/31 • Number of events 9 • 30 days following the 12 weeks of treatment
|
64.5%
20/31 • Number of events 20 • 30 days following the 12 weeks of treatment
|
|
Blood and lymphatic system disorders
Neutropenia (neutrophils)
|
100.0%
6/6 • Number of events 6 • 30 days following the 12 weeks of treatment
|
90.3%
28/31 • Number of events 28 • 30 days following the 12 weeks of treatment
|
93.5%
29/31 • Number of events 29 • 30 days following the 12 weeks of treatment
|
|
Blood and lymphatic system disorders
Thrombocytopenia (platelets)
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
32.3%
10/31 • Number of events 10 • 30 days following the 12 weeks of treatment
|
48.4%
15/31 • Number of events 15 • 30 days following the 12 weeks of treatment
|
|
Investigations
ALT (elevated)
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
12.9%
4/31 • Number of events 4 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
|
General disorders
Chills
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
12.9%
4/31 • Number of events 4 • 30 days following the 12 weeks of treatment
|
16.1%
5/31 • Number of events 5 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Fatigue
|
100.0%
6/6 • Number of events 6 • 30 days following the 12 weeks of treatment
|
100.0%
31/31 • Number of events 31 • 30 days following the 12 weeks of treatment
|
87.1%
27/31 • Number of events 27 • 30 days following the 12 weeks of treatment
|
|
Psychiatric disorders
Insomnia
|
33.3%
2/6 • Number of events 2 • 30 days following the 12 weeks of treatment
|
19.4%
6/31 • Number of events 6 • 30 days following the 12 weeks of treatment
|
16.1%
5/31 • Number of events 5 • 30 days following the 12 weeks of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
100.0%
6/6 • Number of events 6 • 30 days following the 12 weeks of treatment
|
100.0%
31/31 • Number of events 31 • 30 days following the 12 weeks of treatment
|
93.5%
29/31 • Number of events 29 • 30 days following the 12 weeks of treatment
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
25.8%
8/31 • Number of events 8 • 30 days following the 12 weeks of treatment
|
9.7%
3/31 • Number of events 3 • 30 days following the 12 weeks of treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
9.7%
3/31 • Number of events 3 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
3/6 • Number of events 3 • 30 days following the 12 weeks of treatment
|
29.0%
9/31 • Number of events 9 • 30 days following the 12 weeks of treatment
|
29.0%
9/31 • Number of events 9 • 30 days following the 12 weeks of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
83.3%
5/6 • Number of events 5 • 30 days following the 12 weeks of treatment
|
54.8%
17/31 • Number of events 17 • 30 days following the 12 weeks of treatment
|
61.3%
19/31 • Number of events 19 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • Number of events 2 • 30 days following the 12 weeks of treatment
|
45.2%
14/31 • Number of events 14 • 30 days following the 12 weeks of treatment
|
58.1%
18/31 • Number of events 18 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Diarrhea
|
100.0%
6/6 • Number of events 6 • 30 days following the 12 weeks of treatment
|
58.1%
18/31 • Number of events 18 • 30 days following the 12 weeks of treatment
|
58.1%
18/31 • Number of events 18 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Dry mouth
|
66.7%
4/6 • Number of events 4 • 30 days following the 12 weeks of treatment
|
6.5%
2/31 • Number of events 2 • 30 days following the 12 weeks of treatment
|
19.4%
6/31 • Number of events 6 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Flatulence
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
22.6%
7/31 • Number of events 7 • 30 days following the 12 weeks of treatment
|
9.7%
3/31 • Number of events 3 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
50.0%
3/6 • Number of events 3 • 30 days following the 12 weeks of treatment
|
29.0%
9/31 • Number of events 9 • 30 days following the 12 weeks of treatment
|
22.6%
7/31 • Number of events 7 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Mucositis
|
50.0%
3/6 • Number of events 3 • 30 days following the 12 weeks of treatment
|
32.3%
10/31 • Number of events 10 • 30 days following the 12 weeks of treatment
|
19.4%
6/31 • Number of events 6 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Nausea
|
83.3%
5/6 • Number of events 5 • 30 days following the 12 weeks of treatment
|
80.6%
25/31 • Number of events 25 • 30 days following the 12 weeks of treatment
|
93.5%
29/31 • Number of events 29 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Taste alteration
|
83.3%
5/6 • Number of events 5 • 30 days following the 12 weeks of treatment
|
41.9%
13/31 • Number of events 13 • 30 days following the 12 weeks of treatment
|
54.8%
17/31 • Number of events 17 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6 • Number of events 2 • 30 days following the 12 weeks of treatment
|
32.3%
10/31 • Number of events 10 • 30 days following the 12 weeks of treatment
|
61.3%
19/31 • Number of events 19 • 30 days following the 12 weeks of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
45.2%
14/31 • Number of events 14 • 30 days following the 12 weeks of treatment
|
16.1%
5/31 • Number of events 5 • 30 days following the 12 weeks of treatment
|
|
Vascular disorders
Hot flashes
|
50.0%
3/6 • Number of events 3 • 30 days following the 12 weeks of treatment
|
25.8%
8/31 • Number of events 8 • 30 days following the 12 weeks of treatment
|
22.6%
7/31 • Number of events 7 • 30 days following the 12 weeks of treatment
|
|
Infections and infestations
Upper respiratory infection
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
32.3%
10/31 • Number of events 10 • 30 days following the 12 weeks of treatment
|
22.6%
7/31 • Number of events 7 • 30 days following the 12 weeks of treatment
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6 • Number of events 2 • 30 days following the 12 weeks of treatment
|
12.9%
4/31 • Number of events 4 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
100.0%
6/6 • Number of events 6 • 30 days following the 12 weeks of treatment
|
80.6%
25/31 • Number of events 25 • 30 days following the 12 weeks of treatment
|
64.5%
20/31 • Number of events 20 • 30 days following the 12 weeks of treatment
|
|
Eye disorders
Vision changes
|
0.00%
0/6 • 30 days following the 12 weeks of treatment
|
12.9%
4/31 • Number of events 4 • 30 days following the 12 weeks of treatment
|
16.1%
5/31 • Number of events 5 • 30 days following the 12 weeks of treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
12.9%
4/31 • Number of events 4 • 30 days following the 12 weeks of treatment
|
19.4%
6/31 • Number of events 6 • 30 days following the 12 weeks of treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
66.7%
4/6 • Number of events 4 • 30 days following the 12 weeks of treatment
|
41.9%
13/31 • Number of events 13 • 30 days following the 12 weeks of treatment
|
48.4%
15/31 • Number of events 15 • 30 days following the 12 weeks of treatment
|
|
Nervous system disorders
Headache
|
50.0%
3/6 • Number of events 3 • 30 days following the 12 weeks of treatment
|
25.8%
8/31 • Number of events 8 • 30 days following the 12 weeks of treatment
|
16.1%
5/31 • Number of events 5 • 30 days following the 12 weeks of treatment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
35.5%
11/31 • Number of events 11 • 30 days following the 12 weeks of treatment
|
41.9%
13/31 • Number of events 13 • 30 days following the 12 weeks of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
9.7%
3/31 • Number of events 3 • 30 days following the 12 weeks of treatment
|
3.2%
1/31 • Number of events 1 • 30 days following the 12 weeks of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
16.7%
1/6 • Number of events 1 • 30 days following the 12 weeks of treatment
|
22.6%
7/31 • Number of events 7 • 30 days following the 12 weeks of treatment
|
0.00%
0/31 • 30 days following the 12 weeks of treatment
|
Additional Information
Dr. Vered Stearns
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phone: 443-287-6489
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place