Trial Outcomes & Findings for Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer (NCT NCT00477386)

Last Updated: 2014-09-25

Results Overview

The definition of MTD will follow the standard definition of the phase I 3+3 trial concept. Dose Limiting Toxicities (DLTs) will be scored in the first cycle. Patients will be monitored for 28 days (a cycle) to determine whether a DLT is experienced for the specific dose level.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

28 participants

Primary outcome timeframe

28 days

Results posted on

2014-09-25

Participant Flow

Eleven patients were enrolled in the dosing finding Phase I part of the study. The Phase II dose treatment phase had 17 patients enrolled. This was in line with what had been planned.

Participant milestones

Participant milestones
Measure	Phase I Dose Finding Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.	Phase II Decitabine at 10 mg/m2 will be given by IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Overall Study STARTED	11	17
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	11	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I Dose Finding Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.	Phase II Decitabine at 10 mg/m2 will be given by IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Overall Study Adverse Event	4	8
Overall Study Disease progression, relapse	3	4
Overall Study Disease progression, refractory	1	3
Overall Study Other	1	2
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 28 days

Population: All patients assigned to Phase I of the study

Outcome measures

Outcome measures
Measure	Phase I Dose Finding n=11 Participants Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Phase I: Maximum Tolerated Dose (MTD) for Use in Phase II	10 mg/m2 IV QD x 5 days 0 • Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: screening until end of study (approx 12-18 months)

Population: All Patients in Phase II of the study

The percent of patients having an objective response (Complete Response or Partial Response) will be estimated with a 95% exact binomial confidence interval for the percent of patients receiving drug.

Outcome measures

Outcome measures
Measure	Phase I Dose Finding n=17 Participants Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Phase II: Percent of Patients With Objective Response	35.3 percent of participants Interval 14.2 to 61.7

SECONDARY outcome

Timeframe: screening until end of study (approx 12-18 months)

Population: All Patients in Phase II of the study

The percent of patients having an objective response (Complete Response or Partial Response) or CA125 response (Complete Response or Partial Response) or stable disease \> 3 months will be estimated with a 95% exact binomial confidence interval for the percent of patients receiving drug.

Outcome measures

Outcome measures
Measure	Phase I Dose Finding n=17 Participants Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Phase II: Percent of Patients With Objective Response, CA125 Response or Stable Disease > 3 Months	70.6 percent of patients 95% Confidence Interval 0 • Interval 44.0 to 89.7

SECONDARY outcome

Timeframe: Baseline until disease progression or last visit

Population: All Patients in Phase II of the study

Progression free survival times will be estimated using the Kaplan-Meier method. If a patient progresses or dies, the time till that event will be used. If a patient does not progress or die on the study, the patient will be censored at the last available visit. Confidence intervals on the median will be constructed.

Outcome measures

Outcome measures
Measure	Phase I Dose Finding n=17 Participants Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Phase II: Progression Free Survival	10.2 Months 95% Confidence Interval 0 • Interval 1.8 to 14.8

Adverse Events

Phase I Dosing Finding

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Phase II

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Daniela Matai, MD

IndianaU

Phone: 317-944-0920

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase I Dose Finding n=11 Participants Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.	Phase II n=17 Participants Decitabine at 10 mg/m2 will be given by IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.	Total n=28 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	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Age, Continuous	60.8 Years STANDARD_DEVIATION 7.8 • n=5 Participants	61.4 Years STANDARD_DEVIATION 10.9 • n=7 Participants	61.2 Years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

Measure	Phase I Dosing Finding n=11 participants at risk Decitabine at escalating dose levels will be given IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.	Phase II n=17 participants at risk Decitabine at 10 mg/m2 will be given by IV for 1 hour x 5 days followed by Carboplatin given IV for 30 minutes on Day 8 at a dose corresponding to an AUC of 5.
Gastrointestinal disorders CONSTIPATION	0.00% 0/11 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.
Gastrointestinal disorders OBSTRUCTION, GI - SMALL BOWEL NOS	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
General disorders EDEMA: LIMB	0.00% 0/11 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.
General disorders FEBRILE NEUTROPENIA (FEVER OF UNKNOWN ORIGIN WITHOUT CLINICALLY OR MICROBIOLOGICALLY DOCUMENTED INFE	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.
General disorders FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L)	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
General disorders PAIN - HEAD/HEADACHE	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
General disorders PAIN - STOMACH	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
Infections and infestations INFECTION WITH UNKNOWN ANC - SKIN (CELLULITIS)	0.00% 0/11 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.
Investigations NEUTROPHILS/GRANULOCYTES (ANC/AGC)	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.
Respiratory, thoracic and mediastinal disorders PULMONARY/UPPER RESPIRATORY - OTHER (SPECIFY, __)	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
Gastrointestinal disorders HEMORRHAGE, GI - ABDOMEN NOS	0.00% 0/11 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.
Gastrointestinal disorders LEAK (INCLUDING ANASTOMOTIC), GI - SMALL BOWEL	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
Gastrointestinal disorders OBSTRUCTION, GI - DUODENUM	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION (NON-MALIGNANT)	9.1% 1/11 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.	0.00% 0/17 • The AEs were collected from beginning of treatment until the end of study.
Vascular disorders THROMBOSIS/THROMBUS/EMBOLISM	0.00% 0/11 • The AEs were collected from beginning of treatment until the end of study.	5.9% 1/17 • Number of events 1 • The AEs were collected from beginning of treatment until the end of study.