Ixabepilone in Treating Patients With Ovarian Epithelial or Primary Peritoneal Cancer That Has Not Responded to Previous Chemotherapy

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00025155
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 51
• Location: 1
• Arm: 1
• Duration (Months): 92
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of ixabepilone in treating patients who have recurrent or persistent ovarian epithelial or primary peritoneal cancer that has not responded to previous chemotherapy. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die.

Condition or Disease	Intervention/Treatment	Phase
Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer	Drug: ixabepilone	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the antitumor activity of ixabepilone in patients with recurrent or persistent platinum and paclitaxel-refractory ovarian epithelial or primary peritoneal cancer.

2. Determine the nature and degree of toxicity of this drug in these patients.

OUTLINE:

Patients receive ixabepilone IV over 1 hour. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Epothilone-B BMS 247550 (NSC # 710428) in the Treatment of Recurrent or Persistent Platinum and Paclitaxel Refractory Ovarian or Primary Peritoneal Cancer
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ixabepilone) Patients receive ixabepilone IV over 1 hour. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.	Drug: ixabepilone; Given IV; Other Names: BMS-247550 epothilone B lactam Ixempra

Outcome Measures

Primary Outcome Measures

1. Tumor Response [Every other cycle until the completion of study treatment with an average of study treatment time as of 3 months.]

   Percentage of participants with complete and partial tumor response as assessed by the Gynecologic Oncology Group Response Evaluation Criteria in Solid Tumors (GOG RECIST) with one-sided 90% Confidence Interval. Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion, or a 50% decrease in the LD in the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation.

2. Number of People With Adverse Effects [Every cycle until completion of study treatment up to 30 days after stopping study treatment]

Secondary Outcome Measures

1. Progression Free Survival [From study entry to disease progression, death or date of last contact, whichever occurs first. Every other cycle, up to 5 years of follow-up]

   Progression-Free Survival is the period from study entry until disease progression, death or date of last contact, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest dimensions (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or a 50% increase in the LD taking as reference the smallest LD recorded since study entry in the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or death due to disease without prior objective documentation of progression.

2. Overall Survival [From study entry to death or last contact, up to 5 years of follow-up.]

   Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed ovarian epithelial cancer or primary peritoneal cancer

• Recurrent or persistent disease

• Platinum AND taxane-resistant or refractory disease

• Progressed during therapy

• Refractory disease within 6 months of therapy

• Measurable disease

• At least 20 mm by conventional techniques

• At least 10 mm by spiral CT scan

• Tumor lesions located within a previously irradiated field are not considered measurable disease unless there is documented tumor progression in these lesions or biopsy confirmation ≥ 90 days following completion of radiotherapy

• Ineligible for higher priority GOG (Gynecologic Oncology Group) protocol

• No active brain metastases

• Performance status - GOG 0-2

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• SGOT (serum glutamate oxaloacetate transaminase) ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Creatinine ≤ 1.5 times ULN

• No sensory or motor neuropathy > grade 1

• No dementia or altered mental status

• No other serious uncontrolled medical disorder

• No active infection requiring antibiotics

• No prior hypersensitivity reaction to paclitaxel or other therapy containing Cremophor EL

• No other malignancy within the past 5 years except nonmelanoma skin cancer

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• At least 3 weeks since prior biologic therapy

• At least 3 weeks since prior immunotherapy

• Must have received:

• 1 prior combination taxane-based and platinum-based chemotherapy regimen

• 1 prior platinum-based chemotherapy regimen AND 1 prior taxane-based chemotherapy regimen

• Initial treatment may include high-dose therapy, consolidation, or extended therapy

• At least 3 weeks since prior chemotherapy and recovered

• No prior ixabepilone

• No other prior cytotoxic chemotherapy for recurrent or persistent disease, including treatment with initial regimen

• At least 1 week since prior hormonal anticancer therapy

• Concurrent hormone replacement therapy allowed

• At least 3 weeks since prior radiotherapy and recovered

• No prior radiotherapy to site(s) of measurable disease

• No radiotherapy to > 25% of marrow-containing areas

• Recovered from recent surgery

• At least 3 weeks since other anticancer therapy

• No prior anticancer therapy that precludes study participation

• No concurrent food supplements (e.g., St. John's wort)

• No concurrent amifostine or other protective agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gynecologic Oncology Group	Philadelphia	Pennsylvania	United States	19103

Sponsors and Collaborators

• National Cancer Institute (NCI)
• Gynecologic Oncology Group

Investigators

• Principal Investigator: David R. Spriggs, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00025155
• Other Study ID Numbers: NCI-2012-02413; NCI-2012-02413; CDR0000068927; GOG-0126M; GOG-0126M; U10CA027469
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma, Ovarian Epithelial; Epothilones; Epothilone B

Study Results

Participant Flow

Arm/Group Title	Treatment (Ixabepilone)
Arm/Group Description	Patients receive ixabepilone IV over 1 hour on days of 1, 8 and 15 of a 28-day cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.
Period Title: Overall Study
STARTED	51
COMPLETED	49
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Ixabepilone)
Arm/Group Description	Patients receive ixabepilone IV over 1 hour on days of 1, 8 and 15 of a 28-day cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.
Overall Participants	49
Age, Customized (participants) [Number]
20-29 years	1 2%
30-39 years	0 0%
40-49 years	6 12.2%
50-59 years	13 26.5%
60-69 years	15 30.6%
70-79 years	13 26.5%
80-89 years	1 2%
Sex: Female, Male (Count of Participants)
Female	49 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	49 100%
International Federation of Gynecology and Obstetrics (FIGO) Stage - Recurrent/Persistent (participants) [Number]
Number [participants]	49 100%
Histologic Type (participants) [Number]
Adenocarcinoma, unspecified	1 2%
Clear Cell Carcinoma	4 8.2%
Endometrioid Adenocarcinoma	2 4.1%
Mixed Epithelial Carcinoma	3 6.1%
Mucinous Adenocarcinoma	1 2%
Serous Adenocarcinoma	38 77.6%

Outcome Measures

1. Primary Outcome

Title	Tumor Response
Description	Percentage of participants with complete and partial tumor response as assessed by the Gynecologic Oncology Group Response Evaluation Criteria in Solid Tumors (GOG RECIST) with one-sided 90% Confidence Interval. Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), >=30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion, or a 50% decrease in the LD in the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation.
Time Frame	Every other cycle until the completion of study treatment with an average of study treatment time as of 3 months.

Outcome Measure Data

Analysis Population Description

Eligible and treated participants.

Arm/Group Title	Treatment (Ixabepilone)
Arm/Group Description	Patients receive ixabepilone IV over 1 hour on days of 1, 8 and 15 of a 28-day cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.
Measure Participants	49
Number (90% Confidence Interval) [percentage of participants]	14.3 29.2%

2. Primary Outcome

Title	Number of People With Adverse Effects
Time Frame	Every cycle until completion of study treatment up to 30 days after stopping study treatment

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Grade 0	Grade 1	Grade 2	Grade 3	Grade 4
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Toxicity Criteria version 2.0	Number of patients who experienced a grade 2 event using Common Toxicity Criteria version 2.0	Number of patients who experienced a grade 3 event using Common Toxicity Criteria version 2.0	Number of patients who experienced a grade 4 event using Common Toxicity Criteria version 2.0
Measure Participants	49	49	49	49	49
Leukopenia	13 26.5%	9 NaN	20 NaN	6 NaN	1 NaN
Thrombocytopenia	39 79.6%	10 NaN	0 NaN	0 NaN	0 NaN
Neutropenia	17 34.7%	10 NaN	12 NaN	9 NaN	1 NaN
Anemia	9 18.4%	23 NaN	13 NaN	4 NaN	0 NaN
Hematologic	43 87.8%	0 NaN	3 NaN	3 NaN	0 NaN
Allergy	46 93.9%	1 NaN	2 NaN	0 NaN	0 NaN
Cardiovascular	45 91.8%	3 NaN	0 NaN	1 NaN	0 NaN
Coagulation	47 95.9%	0 NaN	0 NaN	2 NaN	0 NaN
Fatigue	11 22.4%	16 NaN	15 NaN	6 NaN	1 NaN
Dermatologic	23 46.9%	13 NaN	13 NaN	0 NaN	0 NaN
Endocrine	48 98%	1 NaN	0 NaN	0 NaN	0 NaN
Gastrointestinal	10 20.4%	15 NaN	14 NaN	9 NaN	1 NaN
Genitourinary/Renal	41 83.7%	6 NaN	1 NaN	1 NaN	0 NaN
Hemorrhage	48 98%	1 NaN	0 NaN	0 NaN	0 NaN
Hepatic	36 73.5%	10 NaN	2 NaN	1 NaN	0 NaN
Infection	43 87.8%	2 NaN	2 NaN	2 NaN	0 NaN
Metabolic	36 73.5%	6 NaN	3 NaN	4 NaN	0 NaN
Neurologic	20 40.8%	12 NaN	14 NaN	3 NaN	0 NaN
Ocular	48 98%	0 NaN	1 NaN	0 NaN	0 NaN
Pain	29 59.2%	10 NaN	8 NaN	1 NaN	1 NaN
Pulmonary	37 75.5%	1 NaN	9 NaN	2 NaN	0 NaN

3. Secondary Outcome

Title	Progression Free Survival
Description	Progression-Free Survival is the period from study entry until disease progression, death or date of last contact, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest dimensions (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or a 50% increase in the LD taking as reference the smallest LD recorded since study entry in the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or death due to disease without prior objective documentation of progression.
Time Frame	From study entry to disease progression, death or date of last contact, whichever occurs first. Every other cycle, up to 5 years of follow-up

Outcome Measure Data

Analysis Population Description

Eligible and treated participants.

Arm/Group Title	Treatment (Ixabepilone)
Arm/Group Description	Patients receive ixabepilone IV over 1 hour on days of 1, 8 and 15 of a 28-day cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.
Measure Participants	49
Median (95% Confidence Interval) [Months]	4.4

4. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Time Frame	From study entry to death or last contact, up to 5 years of follow-up.

Outcome Measure Data

Analysis Population Description

Eligible and treated participants.

Arm/Group Title	Treatment (Ixabepilone)
Arm/Group Description	Patients receive ixabepilone IV over 1 hour on days of 1, 8 and 15 of a 28-day cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.
Measure Participants	49
Median (95% Confidence Interval) [Months]	14.8

Adverse Events

Time Frame	All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported.
Arm/Group Title	Treatment (Ixabepilone)
Arm/Group Description	Patients receive ixabepilone IV over 1 hour on days of 1, 8 and 15 of a 28-day cycle. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR.
All Cause Mortality
	Treatment (Ixabepilone)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Ixabepilone)
	Affected / at Risk (%)	# Events
Total	16/49 (32.7%)
Blood and lymphatic system disorders
Anemia	1/49 (2%)
Cardiac disorders
Thrombosis Embolism	2/49 (4.1%)
Gastrointestinal disorders
Ascites Non-Malignant	1/49 (2%)
Diarrhea Without Colostomy	1/49 (2%)
Constipation	1/49 (2%)
Dehydration	1/49 (2%)
Nausea	1/49 (2%)
GI Other	1/49 (2%)
General disorders
Rigors Chills	1/49 (2%)
Hepatobiliary disorders
Hypoalbuminemia	1/49 (2%)
Infections and infestations
Infection Without Neutropenia	3/49 (6.1%)
Metabolism and nutrition disorders
Hypokalemia	1/49 (2%)
Renal and urinary disorders
Creatinine	1/49 (2%)
Incontinence	1/49 (2%)
Proteinuria	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Voice Changes/Stridor/Larynx	1/49 (2%)
Hypoxia	1/49 (2%)
Pleural Effusion	1/49 (2%)
Skin and subcutaneous tissue disorders
Nail Changes	1/49 (2%)
Other (Not Including Serious) Adverse Events
	Treatment (Ixabepilone)
	Affected / at Risk (%)	# Events
Total	49/49 (100%)
Blood and lymphatic system disorders
Neutropenia	32/49 (65.3%)
Thrombocytopenia	10/49 (20.4%)
Lymphopenia	3/49 (6.1%)
Leukopenia	36/49 (73.5%)
Transfusion Prbc's	4/49 (8.2%)
Anemia	42/49 (85.7%)
Lymphatics Other	1/49 (2%)
Lymphatics	3/49 (6.1%)
Cardiac disorders
Hypotension	1/49 (2%)
Sinus Tachycardia	1/49 (2%)
Edema	4/49 (8.2%)
Thrombosis Embolism	1/49 (2%)
Hypertension	4/49 (8.2%)
Ear and labyrinth disorders
Inner Ear/Hearing	1/49 (2%)
Endocrine disorders
Hot Flashes/Flushes	2/49 (4.1%)
Eye disorders
Vision Blurred	1/49 (2%)
Gastrointestinal disorders
Sense Of Smell	1/49 (2%)
Anorexia	13/49 (26.5%)
Flatulence	3/49 (6.1%)
Mouth Dryness	1/49 (2%)
Gastritis	1/49 (2%)
Colitis	1/49 (2%)
Dyspepsia/Heartburn	5/49 (10.2%)
Taste Disturbance	7/49 (14.3%)
Dysphagia Esophagitis Odynophagia	1/49 (2%)
Diarrhea Without Colostomy	21/49 (42.9%)
Constipation	16/49 (32.7%)
Mucositis Rt	1/49 (2%)
Stomatitis/Pharyngitis	3/49 (6.1%)
Dehydration	6/49 (12.2%)
Vomitting	12/49 (24.5%)
Nausea	22/49 (44.9%)
Gi Other	4/49 (8.2%)
General disorders
Fever(No Neutropenia)	3/49 (6.1%)
Weight Loss	5/49 (10.2%)
Rigors Chills	1/49 (2%)
Weight Gain(No Vod)	1/49 (2%)
Constitutional Symptoms Other	1/49 (2%)
Fatigue	39/49 (79.6%)
Abdominal Pain	14/49 (28.6%)
Pain Other	5/49 (10.2%)
Pain Tumor	2/49 (4.1%)
Neuropathic Pain	1/49 (2%)
Headache	6/49 (12.2%)
Pelvic Pain	2/49 (4.1%)
Chest Pain	2/49 (4.1%)
Bone Pain	1/49 (2%)
Arthralgia	7/49 (14.3%)
Myalgia	7/49 (14.3%)
Pain Rectal/Perirectal	1/49 (2%)
Syndromes Other	1/49 (2%)
Hepatobiliary disorders
Ggt(Gamma-Glutamyltranspeptidase)	2/49 (4.1%)
Hepatic Other	1/49 (2%)
Hypoalbuminemia	4/49 (8.2%)
Sgot(Alt)	4/49 (8.2%)
Sgot(Ast)	8/49 (16.3%)
Alkaline Phosphatase	7/49 (14.3%)
Bilirubin	1/49 (2%)
Immune system disorders
Allergic Rhinitis	1/49 (2%)
Allergic Reaction	3/49 (6.1%)
Infections and infestations
Infection Without Neutropenia	10/49 (20.4%)
Febrile With Neutropenia	1/49 (2%)
Metabolism and nutrition disorders
Hypophosphatemia	3/49 (6.1%)
Metabolic Other	3/49 (6.1%)
Hyponatremia	7/49 (14.3%)
Hypocalcemia	3/49 (6.1%)
Hypermagnesemia	1/49 (2%)
Hyperkalemia	1/49 (2%)
Hyperglycemia	10/49 (20.4%)
Hypokalemia	5/49 (10.2%)
Hypercalcemia	2/49 (4.1%)
Hypomagnesmia	11/49 (22.4%)
Nervous system disorders
Extrapyramidal	1/49 (2%)
Confusion	3/49 (6.1%)
Mood Alteration Anxiety/Agitation	5/49 (10.2%)
Memory Loss	1/49 (2%)
Insomnia	5/49 (10.2%)
Dizziness	3/49 (6.1%)
Mood Alteration Depression	5/49 (10.2%)
Neuropathy Cranial	1/49 (2%)
Neuropathy Sensor	29/49 (59.2%)
Neuropathy Motor	2/49 (4.1%)
Renal and urinary disorders
Urinary Frequency/Urgency	2/49 (4.1%)
Dysuria	1/49 (2%)
Creatinine	3/49 (6.1%)
Renal/Gu Other	1/49 (2%)
Incontinence	1/49 (2%)
Proteinuria	1/49 (2%)
Respiratory, thoracic and mediastinal disorders
Voice Changes/Stridor/Larynx	3/49 (6.1%)
Hypoxia	1/49 (2%)
Pulmonary Other	3/49 (6.1%)
Cough	3/49 (6.1%)
Pneumonitis/Pulmonary Infiltrates	1/49 (2%)
Pleural Effusion	2/49 (4.1%)
Dyspnea	12/49 (24.5%)
Skin and subcutaneous tissue disorders
Alopecia	20/49 (40.8%)
Rash Desquamation	6/49 (12.2%)
Skin Other	1/49 (2%)
Nail Changes	6/49 (12.2%)
Flushing	1/49 (2%)
Bruising	1/49 (2%)
Dry Skin	3/49 (6.1%)
Vascular disorders
Prothrombin Time	2/49 (4.1%)
Partial Thromboplastin Time	2/49 (4.1%)
Rectal Bleeding/Hematochezia	1/49 (2%)
Hematuria No Vaginal Bleeding	2/49 (4.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.