Trial Outcomes & Findings for Vorinostat, Carboplatin and Gemcitabine in Women With Recurrent, Platinum-Sensitive Ovarian Cancer (NCT NCT00910000)
NCT ID: NCT00910000
Last Updated: 2018-09-10
Results Overview
The Vorinostat MTD is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
15 participants
Primary outcome timeframe
The DLT observation period in determining the MTD was the 21-day cycle 1 length.
Results posted on
2018-09-10
Participant Flow
15 participants were enrolled and treated between July 2009 and January 2013. One patient excluded from all analyses failed screening after consent because of elevated liver function tests and did not receive treatment.
Participant milestones
| Measure |
Dose Level 1A
Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2A
Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1B
Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1C
Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1D
Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2D
Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
2
|
3
|
1
|
|
Overall Study
COMPLETED
|
3
|
0
|
0
|
0
|
2
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
3
|
2
|
1
|
1
|
Reasons for withdrawal
| Measure |
Dose Level 1A
Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2A
Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1B
Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1C
Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1D
Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2D
Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
3
|
2
|
2
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
1
|
0
|
Baseline Characteristics
Vorinostat, Carboplatin and Gemcitabine in Women With Recurrent, Platinum-Sensitive Ovarian Cancer
Baseline characteristics by cohort
| Measure |
Dose Level 1A
n=3 Participants
Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2A
n=3 Participants
Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1B
n=3 Participants
Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1C
n=2 Participants
Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1D
n=3 Participants
Vorinostat: 300mg, taken orally once a day for days 1 and 2 of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2D
n=1 Participants
Vorinostat: 400mg, taken orally once a day for days 1 and 2 of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Customized
Age
|
59 years
n=5 Participants
|
63 years
n=7 Participants
|
59 years
n=5 Participants
|
54.5 years
n=4 Participants
|
67 years
n=21 Participants
|
63 years
n=10 Participants
|
60 years
n=115 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
15 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
2 participants
n=4 Participants
|
3 participants
n=21 Participants
|
1 participants
n=10 Participants
|
15 participants
n=115 Participants
|
PRIMARY outcome
Timeframe: The DLT observation period in determining the MTD was the 21-day cycle 1 length.Population: Per protocol, MTD evaluable participants received day 1 of treatment, were not taken off study during cycle 1 due to disease progression, showed proof via pill diary that all doses of vorinostat were taken or attempted to be taken and were compliant with study procedures. The final MTD dataset was comprised of all enrolled and treated participants.
The Vorinostat MTD is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached.
Outcome measures
| Measure |
Dose Level 2D
Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1A
n=15 Participants
Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2A
Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1B
Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1C
Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1D
Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|---|---|---|---|---|
|
Vorinostat Maximum Tolerated Dose (MTD) [Phase Ib]
|
—
|
NA mg/day
Protocol was amended to add reduced V. total dose when 2 of 3 participants in DL 2A, 1B \& 1C experienced DLTs. MTD was not reached w/ the study term early due to safety concerns when the first patient in the dose level cohort 2D experienced a DLT.
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: The DLT observation period in determining the MTD was the 21-day cycle 1 length.Population: Per protocol, DLT evaluable participants received day 1 of treatment, were not taken off study during cycle 1 due to disease progression, showed proof via pill diary that all doses of vorinostat were taken or attempted to be taken and were compliant with study procedures. The final DLT dataset was comprised of all enrolled and treated participants.
Dose-limiting toxicity was based on the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) and defined as any of the following: 1. Any CTCAE grade 3 or 4 non-hematologic event except manageable gastrointestinal toxicity and fatigue. 2. Any of the following hematologic events (excluding neutropenia lasting \< 5 days): i) febrile neutropenia defined as grade 3-4 neutropenia with fever ≥ 38.5°C and/or infection. ii) any grade 4 neutropenia lasting 5 days or more. iii) grade 4 thrombocytopenia (plt count \< 25x 109/L) iv) failure of ANC to recover to ≥ 1000/μL or platelets to recover to ≥ 50,000/μL within 14 days of therapy v) grade 4 anemia 3. Any clinically significant abnormal laboratory value that results in dose delay of \>14 days. 4. \<75% of vorinostat dosing taken by the patient during the first cycle due to any toxicity.
Outcome measures
| Measure |
Dose Level 2D
n=1 Participants
Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1A
n=3 Participants
Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2A
n=3 Participants
Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1B
n=3 Participants
Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1C
n=2 Participants
Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1D
n=3 Participants
Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|---|---|---|---|---|
|
Dose Limiting Toxicity (DLT) [Phase Ib]
|
1 participants with DLT
|
0 participants with DLT
|
2 participants with DLT
|
2 participants with DLT
|
2 participants with DLT
|
0 participants with DLT
|
SECONDARY outcome
Timeframe: Disease was assessed radiographically (CT or MRI scan) every 2 cycles on treatment; Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).Response was based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD from the smallest LD recorded on treatment. Stable disease (SD) is neither sufficient increase to qualify as PD nor sufficient shrinkage to qualify for PR. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed 4 weeks +/- 2 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Participants who received therapy but did not have their disease re-evaluated were considered unevaluable.
Outcome measures
| Measure |
Dose Level 2D
n=1 Participants
Vorinostat: 400mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1A
n=3 Participants
Vorinostat: 200 mg taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 100 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 2A
n=3 Participants
Vorinostat: 300mg, taken orally once a day for the first two weeks of each three-week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1B
n=3 Participants
Vorinostat: 200mg, taken orally twice a day for days 1-3 and days 8-10 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 1 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 1 and day 8 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1C
n=2 Participants
Vorinostat: 200mg, taken orally twice a day for days 1, 2, 8 and 9 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
Dose Level 1D
n=3 Participants
Vorinostat: 300mg, taken orally once a day for days 1 and 2 of every three week cycle
Carboplatin: AUC 4, given intravenously on day 2 of every three week cycle
Gemcitabine: 1000 mg/m2, given intravenously on day 2 and day 9 of every three week cycle
Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|---|---|---|---|---|
|
Response
Complete Response
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Response
Partial Response
|
0 participants
|
3 participants
|
0 participants
|
0 participants
|
1 participants
|
2 participants
|
|
Response
Stable Disease
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Response
Progressive Disease
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Response
Unevaluable
|
1 participants
|
0 participants
|
2 participants
|
3 participants
|
1 participants
|
1 participants
|
Adverse Events
All Phase Ib Participants
Serious events: 9 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Phase Ib Participants
n=15 participants at risk
All Phase Ib participants received Vorinostat according to the established dose escalation schedule during a 3-week cycle in combination with IV carboplatin AUC 4 (day 2) and IV gemcitabine 1000 mg/m2 (days 2 and 9). Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|
|
General disorders
Fatigue
|
13.3%
2/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Blood and lymphatic system disorders
Neutrophils
|
60.0%
9/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Blood and lymphatic system disorders
Platelets
|
53.3%
8/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Blood and lymphatic system disorders
Leukocyte
|
13.3%
2/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Immune system disorders
Allergic Reactions
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Vascular disorders
Pulmonary Embolism
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Metabolism and nutrition disorders
Anorexia
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
Other adverse events
| Measure |
All Phase Ib Participants
n=15 participants at risk
All Phase Ib participants received Vorinostat according to the established dose escalation schedule during a 3-week cycle in combination with IV carboplatin AUC 4 (day 2) and IV gemcitabine 1000 mg/m2 (days 2 and 9). Participants received up to 8 cycles of therapy without the occurrence of disease progression, unacceptable adverse events, patient withdrawal, or discontinuation per MD decision.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
20.0%
3/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
General disorders
Fatigue
|
80.0%
12/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Gastrointestinal disorders
Nausea
|
86.7%
13/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Blood and lymphatic system disorders
Platelets
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Gastrointestinal disorders
Diarrhea
|
53.3%
8/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Gastrointestinal disorders
Constipation
|
33.3%
5/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Investigations
Hypomagnesemia
|
33.3%
5/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Blood and lymphatic system disorders
Leukocyte
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Blood and lymphatic system disorders
Anemia
|
20.0%
3/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
General disorders
Alopecia
|
20.0%
3/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Immune system disorders
Allergic Reactions
|
6.7%
1/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Skin and subcutaneous tissue disorders
Bruising
|
13.3%
2/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Gastrointestinal disorders
Vomiting
|
13.3%
2/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
Nervous system disorders
Neuropathy
|
13.3%
2/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
|
General disorders
Phlebitis
|
13.3%
2/15 • Adverse events were assessed every cycle on treatment. Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60