Clinical Trial of Docetaxel in Combination With Gemcitabine in Platinum-Resistant Ovarian Cancer and Primary Peritoneal Carcinoma

• Sponsor: University of Southern California (Other)
• Overall Status: Completed
• CT.gov ID: NCT00183794
• Collaborator: Aventis Pharmaceuticals (Industry), Eli Lilly and Company (Industry)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 90
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is for patients with advanced ovarian cancer that has reappeared after treatment with conventional therapy. The purpose of this study is to determine if the combination of docetaxel and gemcitabine will be effective in reducing or eliminating the tumor(s) in patients with ovarian cancer.

Docetaxel is approved by the Food and Drug Administration (FDA) for the treatment of breast and lung cancer; gemcitabine is approved by the FDA for the treatment of pancreatic and lung cancer. Neither docetaxel nor gemcitabine are approved for the treatment of ovarian cancer. Both drugs have been shown to decrease the size of ovarian cancer tumors.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Carcinoma; Peritoneal Neoplasms	Drug: Docetaxel and Gemcitabine	Phase 2

Detailed Description

Primary Objective:

1. To determine the response rate, time to progression and survival (secondary) of the combination of docetaxel and gemcitabine administered on a weekly basis to patients with platinum-resistant ovarian cancer

Secondary Objective:

1. To determine the toxicity of this combination regimen in patients with platinum-resistant ovarian cancer

2. To evaluate the toxicity and safety profile of a short course (one dose) of premedication with steroids to patients receiving weekly gemcitabine and docetaxel

OUTLINE: Patients receive gemcitabine IV over 30 minutes on days 1 and 8, and docetaxel IV over 60 minutes on day 8. Treatment repeats every 21 days until PD, unacceptable toxicity, or patient's withdrawal.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Clinical Trial of Docetaxel in Combination With Gemcitabine in Platinum-Resistant Ovarian Cancer and Primary Peritoneal Carcinoma
• Study Start Date: Nov 1, 2002
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Patients will receive Docetaxel 75mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8. Cycles will be repeated every 3 weeks.	Drug: Docetaxel and Gemcitabine; Docetaxel 75 mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8 of each 3 weeks (21 days) cycle.

Outcome Measures

Primary Outcome Measures

1. Tumor Response Type: CR, PR, SD or PD [6 months after enrollment of last participant]

   Tumor response will be based on the RECIST v1.0 criteria. CR (complete response)= disappearance of all target lesions, PR (partial response)= greater or equal to 30% decrease in sum of longest diameter of target lesions, SD (stable disease)= <30% decrease or <20% increase, PD (progressive disease)= greater or equal to 20% increase in longest diameter of target lesions. For patients with an elevated CA-125 as the only evidence of disease, a PR was defined as a decrease of 50% or more lasting at least 8 weeks (Rustin et al. JCO 14:1545-51, 1996). Disease assessment performed every 2 cycles (1 cycle = 21 days). Responders included CR and PR.

Secondary Outcome Measures

1. Median Time to Progression (Months) [6 months after enrollment of last patient]

   Defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. Progression based on RECIST v1.0 criteria for measurable disease, and on CA-125 for patients with an elevated CA-125 as the only evidence of disease (Rustin et al. JCO 14:1545-51, 1996)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically proven diagnosis of epithelial ovarian ca

• Must have platinum-resistant disease. (Defined as progression during the most recent platinum-based chemotx or relapse < 6 months after the most recent platinum-based chemotx regimen.)

• Measurable or evaluable disease. (Patients whose dz is manifested only as an elevated CA-125 [greater than or equal to 100] are eligible. If an elevated CA-125 is the only manifestation of dz, it must be confirmed on 2 separate times, at least 2 weeks apart. Patients with positive cytology only are not eligible.)

• Greater than or equal to 18 years of age

• GOG performance status less than or equal to 2

• AGC/ANC greater than or equal to 1.5; platelets greater than or equal to 100,000; hemoglobin (Hgb) greater than or equal to 8.0.

• Creatinine less than or equal to 2.0

• Total bilirubin less than or equal to upper limit of normal (uln)

• SGOT and/or SGPT less than or equal to 2.5 x uln if alkaline phosphatase less than or equal to uln, or alkaline phosphatase less than or equal to 4 x uln if transaminases are less than or equal to uln. (If both SGOT/SGPT >1.5 x uln and alkaline phosphatase

2.5 x uln, patient is not eligible.)

• Fully recovered from acute toxicities secondary to prior treatment (tx)

• Signed informed consent

Exclusion Criteria:

• Prior treatment with gemcitabine or docetaxel

• Underlying medical, psychiatric, or social conditions that would preclude patient from receiving treatment

• Peripheral neuropathy greater than or equal to Grade 2

• No prior tx with cisplatin or carboplatin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033

Sponsors and Collaborators

• University of Southern California
• Aventis Pharmaceuticals
• Eli Lilly and Company

Investigators

• Principal Investigator: Agustin Garcia, MD, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Southern California
• ClinicalTrials.gov Identifier: NCT00183794
• Other Study ID Numbers: 5GYN-02-2
• First Posted: Sep 16, 2005
• Last Update Posted: May 22, 2014
• Last Verified: Dec 1, 2012

• Keywords provided by University of Southern California: Primary Peritoneal
• Additional relevant MeSH terms: Carcinoma; Peritoneal Neoplasms; Gemcitabine; Docetaxel

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the USC+LAC Women's Hospital and the USC/Norris Cancer Hospital between December 2002 and April 2008.

Arm/Group Title	Gemcitabine and Docetaxel
Arm/Group Description	Patients will receive Docetaxel 75mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8. Cycles will be repeated every 3 weeks.
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Gemcitabine and Docetaxel
Arm/Group Description	Patients will receive Docetaxel 75mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8. Cycles will be repeated every 3 weeks.
Overall Participants	20
Age (years) [Median (Full Range) ]
Between 43 and 75 years	59
Sex: Female, Male (Count of Participants)
Female	20 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 65%
Not Hispanic or Latino	7 35%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 20%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 20%
More than one race	0 0%
Unknown or Not Reported	12 60%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Tumor Response Type: CR, PR, SD or PD
Description	Tumor response will be based on the RECIST v1.0 criteria. CR (complete response)= disappearance of all target lesions, PR (partial response)= greater or equal to 30% decrease in sum of longest diameter of target lesions, SD (stable disease)= <30% decrease or <20% increase, PD (progressive disease)= greater or equal to 20% increase in longest diameter of target lesions. For patients with an elevated CA-125 as the only evidence of disease, a PR was defined as a decrease of 50% or more lasting at least 8 weeks (Rustin et al. JCO 14:1545-51, 1996). Disease assessment performed every 2 cycles (1 cycle = 21 days). Responders included CR and PR.
Time Frame	6 months after enrollment of last participant

Outcome Measure Data

Analysis Population Description

Participants with evaluable or measurable tumor, who complete 2 courses of treatment will be included in analysis of tumor response.

Arm/Group Title	Gemcitabine and Docetaxel
Arm/Group Description	Patients will receive Docetaxel 75mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8. Cycles will be repeated every 3 weeks.
Measure Participants	20
CR	1 5%
PR	4 20%
SD	9 45%
PD	6 30%

2. Secondary Outcome

Title	Median Time to Progression (Months)
Description	Defined as the time from first day of treatment to the first observation of disease progression or death due to any cause. If a patient has not progressed or died, progression-free survival is censored at the time of last follow-up. Progression based on RECIST v1.0 criteria for measurable disease, and on CA-125 for patients with an elevated CA-125 as the only evidence of disease (Rustin et al. JCO 14:1545-51, 1996)
Time Frame	6 months after enrollment of last patient

Outcome Measure Data

Analysis Population Description

All participants who receive the first course of treatment are included in the summary of PFS.

Arm/Group Title	Gemcitabine and Docetaxel
Arm/Group Description	Patients will receive Docetaxel 75mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8. Cycles will be repeated every 3 weeks.
Measure Participants	20
Median (Full Range) [Months]	3

Adverse Events

Arm/Group Title	Gemcitabine and Docetaxel
Arm/Group Description	Patients will receive Docetaxel 75mg/m2 IV over 15-30 minutes on day 1 followed by Gemcitabine 800 mg/m2 IV over 30 minutes on Days 1 and 8. Cycles will be repeated every 3 weeks.
All Cause Mortality
	Gemcitabine and Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine and Docetaxel
	Affected / at Risk (%)	# Events
Total	12/20 (60%)
Blood and lymphatic system disorders
Anemia	1/20 (5%)	2
Febrile Neutropenia	2/20 (10%)	2
Gastrointestinal disorders
Vomiting	1/20 (5%)	1
General disorders
Fatigue	1/20 (5%)	1
Infections and infestations
Wound Infection	1/20 (5%)	1
Investigations
Alkaline Phosphatase Increased	1/20 (5%)	1
Neutrophil Count Decreased	11/20 (55%)	29
Platelet Count Decreased	1/20 (5%)	2
White Blood Cell Decreased	5/20 (25%)	12
Metabolism and nutrition disorders
Hyperglycemia	1/20 (5%)	2
Hypoalbuminemia	1/20 (5%)	1
Hypophosphatemia	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine and Docetaxel
	Affected / at Risk (%)	# Events
Total	13/20 (65%)
Blood and lymphatic system disorders
Anemia	1/20 (5%)	13
Cardiac disorders
Palpitations	1/20 (5%)	1
Eye disorders
Watering Eyes	1/20 (5%)	1
Gastrointestinal disorders
Nausea	4/20 (20%)	4
Vomiting	2/20 (10%)	2
Ascites	1/20 (5%)	2
Diarrhea	3/20 (15%)	3
Constipation	3/20 (15%)	4
Abdominal Pain	2/20 (10%)	3
Mucosits Oral	2/20 (10%)	4
General disorders
Fatigue	7/20 (35%)	12
Pin	1/20 (5%)	1
Localized Edema	4/20 (20%)	6
Fever	3/20 (15%)	5
Chills	3/20 (15%)	4
Injury, poisoning and procedural complications
Bruising	2/20 (10%)	2
Investigations
Creatinine Increased	1/20 (5%)	1
Neutrophil Count Decreased	1/20 (5%)	12
White Blood Cell Decreased	10/20 (50%)	14
Platelet Count Decreased	7/20 (35%)	13
Blood Bilirubin Increased	1/20 (5%)	1
Alkaline Phosphatase	3/20 (15%)	3
Weight Gain	1/20 (5%)	2
Aspartate Aminotrasferase Increased	3/20 (15%)	5
Alanine Aminotransferase Increased	3/20 (15%)	5
Metabolism and nutrition disorders
Hypocalcemia	1/20 (5%)	1
Hypernatremia	1/20 (5%)	1
Hyperglycemia	3/20 (15%)	5
Hypophosphatemia	1/20 (5%)	1
Hypoalbuminemia	1/20 (5%)	2
Hyponatremia	2/20 (10%)	2
Anorexia	2/20 (10%)	3
Musculoskeletal and connective tissue disorders
Back Pain	1/20 (5%)	2
Nervous system disorders
Peripheral Motor Neuropathy	2/20 (10%)	2
Peripheral Sensory Neuropathy	6/20 (30%)	9
Dizziness	3/20 (15%)	4
Renal and urinary disorders
Urinary Tract Pain	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/20 (15%)	5
Cough	2/20 (10%)	3
Epistaxis	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Alopecia	5/20 (25%)	5
Rash/Acneiform	4/20 (20%)	7
Skin Disorder - Other (specify: skin tear)	1/20 (5%)	1
Nail Discoloration	3/20 (15%)	3
Purpura	1/20 (5%)	1
Vascular disorders
Hot Flashes	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.