Trial Outcomes & Findings for Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Recurrent Advanced Ovarian Epithelial or Peritoneal Cavity Cancer (NCT NCT00093496)

Last Updated: 2014-05-20

Results Overview

Objective response will be measured using the modified RECIST criteria. A confirmed response requires an objective status of complete or partial response on 2 consecutive evaluations occurring 4 or more weeks apart. Complete Response (CR): Disappearance of all target lesions and normalization of tumor biomarkers. Partial Response (PR): At least a 30% decrease in the sum of the target lesions from the baseline.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

Participants were evaluated every 6 weeks on treatment, with median treatment length of 12 weeks (3 week minimum and 42 week maximum).

Results posted on

2014-05-20

Participant Flow

Twenty-nine patients were enrolled between November 15, 2007 and October 29, 2009. Two participants were found to be ineligible and two participants had major protocol violations. Therefore, we summarize baseline characteristics and adverse events using all 29 patients, but report endpoint analyses using 25 participants.

Participants were divided into two groups according to their prior gemcitabine exposure. Cohort 1 participants had no prior exposure to gemcitabine. Cohort 2 was comprised of participants with prior exposure to gemcitabine as a single agent or had experienced disease progression while on gemcitabine therapy.

Participant milestones

Participant milestones
Measure	Cohort 1 (No Prior Gemcitabine Exposure) Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Overall Study STARTED	15	14
Overall Study COMPLETED	14	11
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 (No Prior Gemcitabine Exposure) Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Overall Study Protocol Violation	1	3

Baseline Characteristics

Gemcitabine Hydrochloride and Tanespimycin in Treating Patients With Recurrent Advanced Ovarian Epithelial or Peritoneal Cavity Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (No Prior Gemcitabine Exposure) n=15 Participants Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) n=14 Participants Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Total n=29 Participants Total of all reporting groups
Age, Continuous	64 years n=5 Participants	63.5 years n=7 Participants	64 years n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	14 participants n=7 Participants	29 participants n=5 Participants

PRIMARY outcome

Timeframe: Participants were evaluated every 6 weeks on treatment, with median treatment length of 12 weeks (3 week minimum and 42 week maximum).

Population: In Cohort 1, one patient was found to be ineligible. In Cohort 2, one patient was ineligible and two patients had protocol violations. Therefore, 14 participants in Cohort 1 and eleven participants in Cohort 2 were analyzed for the primary endpoint.

Outcome measures

Outcome measures
Measure	Cohort 1 (No Prior Gemcitabine Exposure) n=14 Participants Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) n=11 Participants Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Proportion of Patients Who Experience a Confirmed Response According to Modified RECIST Criteria. Confirmed Partial Response (PR)	0.071 proportion of participants	0 proportion of participants
Proportion of Patients Who Experience a Confirmed Response According to Modified RECIST Criteria. Confirmed Complete Response (CR)	0 proportion of participants	0 proportion of participants

SECONDARY outcome

Timeframe: Participants were evaluated every 6 weeks on treatment (maximum 42 weeks), and followed up to 5 years from registration.

Population: An interim analysis was done on the first 12 eligible participants in each cohort. Due to drug shortage and lack of clinical activity, the interim analysis for Cohort 2 was conducted on the first 11 participants.

Defined as the time from registration to the date of progression or last follow-up, whichever comes first. Estimated using the method of Kaplan-Meier

Outcome measures

Outcome measures
Measure	Cohort 1 (No Prior Gemcitabine Exposure) n=12 Participants Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) n=11 Participants Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Times to Progression	1.6 months Interval 1.2 to 3.5	2.7 months Interval 1.3 to 5.1

SECONDARY outcome

Timeframe: Every 3 months until disease progression and then every 6 months for up to 5 years.

Population: An interim analysis was done on the first 12 eligible participants in each cohort. Due to drug shortage and lack of clinical acttivity, the interim analysis for Cohort 2 was conducted on the first 11 participants.

Defined as the time from registration to date of last follow-up or death due to any cause. Estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Cohort 1 (No Prior Gemcitabine Exposure) n=12 Participants Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) n=11 Participants Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Overall Survival	18.3 months Interval 6.2 to There was not a sufficient number of events to estimate the upper 95% confidency level.	11.5 months Interval 4.0 to 13.7

SECONDARY outcome

Timeframe: Participants were evaluated every 6 weeks on treatment (maximum 42 weeks)

Defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 as an adverse event classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Outcome measures

Outcome measures
Measure	Cohort 1 (No Prior Gemcitabine Exposure) n=14 Participants Patients with no prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.	Cohort 2 (Prior Gemcitabine Exposure) n=11 Participants Patients with prior gemcitabine exposure receive tanespimycin IV over 2 hours on days 1 and 8 during course 1 and days 2 and 9 during subsequent courses and gemcitabine hydrochloride IV over 30 minutes on day 7 during course 1 and days 1 and 8 during subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression and then every 6 months for up to 5 years.
Toxicity Grade 3	9 events	7 events
Toxicity Grade 4 or Higher	0 events	0 events

Adverse Events

All Patients Receiving Gemcitabine

Serious events: 10 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Patients Receiving Gemcitabine n=29 participants at risk All patients receiving gemcitabine were combined to analyze toxicity.
Blood and lymphatic system disorders Hemoglobin decreased	3.4% 1/29 • Number of events 1
Gastrointestinal disorders Abdominal pain	3.4% 1/29 • Number of events 1
Gastrointestinal disorders Nausea	6.9% 2/29 • Number of events 5
Gastrointestinal disorders Small intestinal obstruction	3.4% 1/29 • Number of events 2
Gastrointestinal disorders Vomiting	6.9% 2/29 • Number of events 2
General disorders Edema limbs	3.4% 1/29 • Number of events 1
Infections and infestations Urinary tract infection	6.9% 2/29 • Number of events 2
Investigations Alkaline phosphatase increased	3.4% 1/29 • Number of events 1
Investigations Aspartate aminotransferase increased	3.4% 1/29 • Number of events 1
Investigations Creatinine increased	3.4% 1/29 • Number of events 1
Investigations Leukocyte count decreased	3.4% 1/29 • Number of events 1
Investigations Neutrophil count decreased	10.3% 3/29 • Number of events 5
Nervous system disorders Headache	3.4% 1/29 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	3.4% 1/29 • Number of events 1
Skin and subcutaneous tissue disorders Rash desquamating	3.4% 1/29 • Number of events 1

Other adverse events

Other adverse events
Measure	All Patients Receiving Gemcitabine n=29 participants at risk All patients receiving gemcitabine were combined to analyze toxicity.
Blood and lymphatic system disorders Hemoglobin decreased	82.8% 24/29 • Number of events 79
Gastrointestinal disorders Abdominal pain	10.3% 3/29 • Number of events 6
Gastrointestinal disorders Constipation	10.3% 3/29 • Number of events 8
Gastrointestinal disorders Diarrhea	31.0% 9/29 • Number of events 15
Gastrointestinal disorders Flatulence	3.4% 1/29 • Number of events 1
Gastrointestinal disorders Gastric ulcer	3.4% 1/29 • Number of events 1
Gastrointestinal disorders Nausea	55.2% 16/29 • Number of events 26
Gastrointestinal disorders Stomach pain	3.4% 1/29 • Number of events 3
Gastrointestinal disorders Vomiting	34.5% 10/29 • Number of events 13
General disorders Edema limbs	3.4% 1/29 • Number of events 3
General disorders Fatigue	24.1% 7/29 • Number of events 19
Injury, poisoning and procedural complications Dermatitis radiation	3.4% 1/29 • Number of events 1
Investigations Alkaline phosphatase increased	20.7% 6/29 • Number of events 9
Investigations Aspartate aminotransferase increased	27.6% 8/29 • Number of events 12
Investigations Leukocyte count decreased	48.3% 14/29 • Number of events 29
Investigations Neutrophil count decreased	58.6% 17/29 • Number of events 33
Investigations Platelet count decreased	31.0% 9/29 • Number of events 22
Metabolism and nutrition disorders Anorexia	13.8% 4/29 • Number of events 9
Nervous system disorders Dizziness	6.9% 2/29 • Number of events 2
Nervous system disorders Peripheral motor neuropathy	3.4% 1/29 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	10.3% 3/29 • Number of events 3
Respiratory, thoracic and mediastinal disorders Cough	27.6% 8/29 • Number of events 15
Respiratory, thoracic and mediastinal disorders Dyspnea	13.8% 4/29 • Number of events 7
Skin and subcutaneous tissue disorders Alopecia	17.2% 5/29 • Number of events 10
Skin and subcutaneous tissue disorders Nail disorder	3.4% 1/29 • Number of events 3
Skin and subcutaneous tissue disorders Rash desquamating	3.4% 1/29 • Number of events 2

Additional Information

Charles Erlichman, M.D.

Mayo Clinic Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60