Trial Outcomes & Findings for Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer (NCT NCT00702962)

Last Updated: 2018-10-22

Results Overview

To estimate the maximum tolerated dose of vorinostat using a traditional dose escalation schedule ("3 + 3 design). MTD is determined by assessing for specific predefined dose limiting toxicities. A starting dose of vorinostat 200mg was combined with carboplatin and etoposide. Dose escalation went in increments of 100mg (i.e. 300mg, 400mg).

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

2 years, not analyzed

Results posted on

2018-10-22

Participant Flow

Open to accrual 09/2008 as Phase I study. Three participants treated with dose level 1. Similar NCI-CTEP Phase I trial (NCI 8703) established the maximum tolerated dose (MTD) for the study drug. This study was amended to Phase II using the NCI established dose. One participant treated on Phase II. Closed to accrual 01/2012 due to low enrollment.

Eight patients total were consented (i.e. "enrolled"). Three of the 8 were determined to be ineligible upon screening. One of the 8 was eligible but subsequently declined participation soon after signing consent. Four (4) of 8 enrolled went to active treatment ("started"). Of these 4, 3 participated in Phase I and 1 participated in Phase II.

Participant milestones

Participant milestones
Measure	Phase II Portion - Vorinostat 300mg Phase 2 is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with vorinostat.Vorinostat, Carboplatin, Etoposide, SAHA SAHA: Once the recommended phase II dose has been established and additional 15 patients will be enrolled. Days 1-4 Vorinostat recommended phase II dose po QD;Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. An additional 35 patients on the phase II portion of the trial will be required to achieve the outlined objectives.	Phase I Portion - Vorinostat 200mg Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 Vorinostat, Carboplatin, Etoposide, SAHA. Vorinostat, Carboplatin, Etoposide: Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. Phase I was prematurely closed as an NCI study established the MTD. This study proceeded to Phase II soon after the first participant was enrolled at Dose Level 2 (300mg).
Overall Study STARTED	1	3
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase II Portion - Vorinostat 300mg Phase 2 is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with vorinostat.Vorinostat, Carboplatin, Etoposide, SAHA SAHA: Once the recommended phase II dose has been established and additional 15 patients will be enrolled. Days 1-4 Vorinostat recommended phase II dose po QD;Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. An additional 35 patients on the phase II portion of the trial will be required to achieve the outlined objectives.	Phase I Portion - Vorinostat 200mg Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3 Vorinostat, Carboplatin, Etoposide, SAHA. Vorinostat, Carboplatin, Etoposide: Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. Phase I was prematurely closed as an NCI study established the MTD. This study proceeded to Phase II soon after the first participant was enrolled at Dose Level 2 (300mg).
Overall Study Progressive disease	0	1
Overall Study Hospitalized for other health disorder	1	0

Baseline Characteristics

Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PHASE I: Vorinostat 200mg Carbo 6 (AUC) n=3 Participants Phase I portion: To determine MTD of Vorinostat when used in combination with other chemotherapy. Start at Vorinostat 200 mg PO QD D1-14; Carbo 6 (AUC) D3; Etoposide 100 mg/m2 D1,2,3; Vorinostat, Carboplatin, Etoposide, SAHA Vorinostat, Carboplatin, Etoposide: Sequential cohorts of 3-6 patients will be entered to the following dose levels: Level 1 - Days 1-14: Vorinostat 200 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Level 2 - Days 1-14: Vorinostat 300 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2; Level 3: Days 1-14: Vorinostat 400 mg po QD; Day 3: Carboplatin 6 AUC; Days 1,2,3: Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient.	PHASE II: Vorinostat 300mg Carbo 6 (AUC) n=1 Participants Phase II portion: To determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide with fixed dose Vorinostat. (Vorinostat, Carboplatin, Etoposide, SAHA) SAHA: Once the recommended phase II dose has been established and additional 15 patients will be enrolled. Days 1-4 Vorinostat recommended phase II dose po QD;Day 3 Carboplatin 6 AUC; Days 1,2,3 Etoposide 100 mg/m2. Treatment cycles will be repeated every 3 weeks. A maximum of 4 cycles will be administered to each patient. An additional 35 patients on the phase II portion of the trial will be required to achieve the outlined objectives.	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	64.3 years STANDARD_DEVIATION 10.8 • n=5 Participants	70 years STANDARD_DEVIATION 0 • n=7 Participants	65.8 years STANDARD_DEVIATION 9.7 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years, not analyzed

Population: The first three participants enrolled were treated at dose level 1 (vorinostat 200 mg). Phase I protocol closed prematurely with no additional subjects enrolled. No analysis due to premature closure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years, not analyzed

Population: One participant enrolled on Phase II. Off treatment and off study prematurely due to concurrent health disorders.

For the purpose of this study, overall survival is defined as the percentage of participants who are alive at two years post initiation of study treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years, not analyzed

Population: One participant enrolled and treated in the Phase II portion. Participant rendered off treatment and off study prior to completion due to concurrent health disorders. The clinical trial closed prematurely due to low accrual. For this reason, an analysis of this secondary objective would not be meaningful. No analysis done.

Eligibility limits the study population to those who have measurable disease pre-treatment. This secondary outcome measure was intended to objectively evaluate disease response and survival rate in recipients of the investigational medication regimen. Disease response was performed using standard diagnostic imaging. Tumor markers and cytology may be used to support the imaging results. Objective response rate was defined as progression-free survival (PFS) among treatment recipients. PFS, is defined as time (in months) from entry to clinical evidence of disease progression or death without progression. The clinical trial closed prematurely due to low accrual. For this reason, an analysis of this secondary objective would not be meaningful. No analysis done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years, not analyzed

Population: One participant enrolled in the Phase II portion and discontinued treatment prematurely due to concurrent health issues and hospitalization. No unanticipated adverse events occurred while on study. The study closed prematurely due to low accrual. No analysis conducted.

Evaluation of resultant adverse events that occurred with participants with extensive disease SCLC after initiating treatment using a fixed dose of vorinostat in combination with carboplatin and etoposide.

Outcome measures

Outcome data not reported

Adverse Events

Phase II: Vorinostat 300mg With Carboplatin and Etoposide

Serious events: 0 serious events

Other events: 1 other events

Deaths: 1 deaths

Phase I: Determine MTD Vorinostat (200mg-400mg)

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Phase II: Vorinostat 300mg With Carboplatin and Etoposide n=1 participants at risk Phase 2 objective is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide using an established dose of Vorinostat. Participants in Phase II received a "cycle" consisting of the NCI recommended Vorinostat dose with Carboplatin 6 AUC and Etoposide 100 mg/m2. Treatment cycles were repeated every 3 weeks. A maximum of 4 cycles were administered. A total of 35 participants were required for Phase II analysis. The Phase II study closed prematurely due to low accrual. Analysis of the primary and secondary objectives was not possible due to inadequate sample size.	Phase I: Determine MTD Vorinostat (200mg-400mg) n=3 participants at risk The original purpose of the Phase I portion was to establish the MTD of Vorinostat when provided with other chemotherapy (Carboplatin and Etoposide). Initial dose at 200mg, then 300, to a max of 400 mg. The first cohort at 200 mg did well with no dose limiting toxicities. After the enrollment of the 1st participant into cohort 2, the Phase I study was prematurely closed as concurrent NCI publications had established appropriate dose levels. The phase I portion was closed after the first 3 participants. Analysis of the objectives is not applicable due to premature closing.
Vascular disorders Thrombophlebitis	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions

Other adverse events

Additional Information

Dr. C. Belani

MSHERSHEY MC

Phone: 717-531-1078

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase II: Vorinostat 300mg With Carboplatin and Etoposide n=1 participants at risk Phase 2 objective is to determine progression free survival among patients with extensive disease SCLC receiving carboplatin plus etoposide using an established dose of Vorinostat. Participants in Phase II received a "cycle" consisting of the NCI recommended Vorinostat dose with Carboplatin 6 AUC and Etoposide 100 mg/m2. Treatment cycles were repeated every 3 weeks. A maximum of 4 cycles were administered. A total of 35 participants were required for Phase II analysis. The Phase II study closed prematurely due to low accrual. Analysis of the primary and secondary objectives was not possible due to inadequate sample size.	Phase I: Determine MTD Vorinostat (200mg-400mg) n=3 participants at risk The original purpose of the Phase I portion was to establish the MTD of Vorinostat when provided with other chemotherapy (Carboplatin and Etoposide). Initial dose at 200mg, then 300, to a max of 400 mg. The first cohort at 200 mg did well with no dose limiting toxicities. After the enrollment of the 1st participant into cohort 2, the Phase I study was prematurely closed as concurrent NCI publications had established appropriate dose levels. The phase I portion was closed after the first 3 participants. Analysis of the objectives is not applicable due to premature closing.
Blood and lymphatic system disorders Leukopenia	100.0% 1/1 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	100.0% 3/3 • Number of events 10 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Blood and lymphatic system disorders Neutropenia	100.0% 1/1 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	100.0% 3/3 • Number of events 11 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Blood and lymphatic system disorders Thrombocytopenia	100.0% 1/1 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	66.7% 2/3 • Number of events 10 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Gastrointestinal disorders Nausea	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	100.0% 3/3 • Number of events 5 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
General disorders Fatigue	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	100.0% 3/3 • Number of events 9 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Blood and lymphatic system disorders Anemia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	100.0% 3/3 • Number of events 4 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 3 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
General disorders Facial flushing	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 3 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Alkaline phosphatase, elevated	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	100.0% 3/3 • Number of events 3 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
General disorders Insomnia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	66.7% 2/3 • Number of events 4 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Infections and infestations Vaginal Candidiasis	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 3 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Alanine aminotransferase (ALT) elevation	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Gastrointestinal disorders Anorexia	100.0% 1/1 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	0.00% 0/3 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Hepatobiliary disorders Hyperbilirubinemia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Skin and subcutaneous tissue disorders Erythema, skin	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	66.7% 2/3 • Number of events 2 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Dizziness	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	66.7% 2/3 • Number of events 2 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Gastrointestinal disorders Dry mouth	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
General disorders Fever without neutropenia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Respiratory, thoracic and mediastinal disorders Hiccoughs	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 2 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Skin and subcutaneous tissue disorders Cellulitis	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Hypermagnesemia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Restlessness with irritibility	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Anxiety	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Abnormal dreams	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Back pain	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 2 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Pain, extremity/limb	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Nervous system disorders Headache	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Gastrointestinal disorders Pain - Throat/pharynx/larynx	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 2 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Hypokalemia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Metabolism and nutrition disorders Hyponatremia	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 3 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions
Skin and subcutaneous tissue disorders Ulceration, vaginal	0.00% 0/1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions	33.3% 1/3 • Number of events 1 • The time period for adverse event collection is from the time of consent to 30 days after last treatment cycle. Per clinicaltrials.gov standard definitions