Irofulven in Treating Patients With Recurrent or Persistent Ovarian Epithelial or Primary Peritoneal Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00053365
• Collaborator: Gynecologic Oncology Group (Other)
• Enrollment: 61
• Location: 1
• Arm: 1
• Duration (Months): 85
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of irofulven in treating patients who have recurrent or persistent ovarian epithelial cancer or primary peritoneal cancer. Drugs used in chemotherapy use 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: irofulven	Phase 2

Detailed Description

OBJECTIVES:

1. Determine the antitumor activity of irofulven in patients with persistent or recurrent platinum-sensitive ovarian epithelial or primary peritoneal cancer.

2. Determine the toxicity of this drug in these patients.

OUTLINE:

Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.

Patients are followed at approximately 30 days, every 3 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: Approximately 22-60 patients will be accrued for this study within at least 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation Of Irofulven (IND #55804, NSC #683863) In The Treatment Of Recurrent Or Persistent Platinium-Sensitive Ovarian Or Primary Peritoneal Cancer
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (irofulven) Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.	Drug: irofulven; Given IV; Other Names: 6-hydroxymethylacylfulvene HMAF MGI 114 MGI-114

Outcome Measures

Primary Outcome Measures

1. Tumor Response [From entry into study until documented progression or death, assessed up to 5 years.]

   Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria: Complete Response is disappearance of all target and non-target lesions; Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable dimensions; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Response is to be evaluated every 42 days for the first 6 months and every 6 months thereafter while the patient is receiving study treatment, then every 3 months for 2 years and every 6 months for the next 3 years until documented progression or death.

2. Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [Assessed every cycle while on treatment, 30 days after the last cycle of treatment]

Secondary Outcome Measures

1. Progression-free Survival [From entry into study to death or date of last contact, assessed up to 5 years]

   Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria, progression is defined as at least a 20% increase in the sum of longest dimesions(LD) of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed ovarian epithelial or primary peritoneal carcinoma

• Recurrent or persistent disease

• At least 1 unidimensionally measurable target lesion* defined as:

• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

• Must have received 1 prior platinum-based chemotherapeutic regimen containing carboplatin, cisplatin, or another organoplatinum compound for primary disease

• Initial treatment may have included high-dose, consolidation, or extended therapy administered after surgical or non-surgical assessment

• Patients who have not received prior paclitaxel may receive a second regimen containing paclitaxel

• Ineligible for a higher priority GOG protocol (e.g., any active phase III GOG protocol for the same patient population)

• Platinum-sensitive disease

• Platinum-free interval** of more than 6 months, but less than 12 months duration, with no clinical evidence of progressive disease after response to platinum

• Performance status - GOG 0-2 for patients who received 1 prior therapy regimen

• Performance status - GOG 0-1 for patients who received 2 prior therapy regimens

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)

• SGOT no greater than 2.5 times ULN

• Alkaline phosphatase no greater than 2.5 times ULN

• Creatinine normal

• Creatinine clearance at least 60 mL/min

• No prior congestive heart failure requiring medication

• No uncontrolled hypertension within the past 6 months

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

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

• No history of retinopathy and/or macular degeneration

• No neuropathy (sensory and motor) greater than grade 1

• No active infection requiring antibiotics

• No other illness or condition that would preclude study entry

• No prior bone marrow or stem cell transplantation

• At least 3 weeks since prior biologic therapy or immunotherapy for malignant tumor

• One prior non-cytotoxic regimen (e.g., monoclonal antibodies, cytokines, or small-molecule signal transduction inhibitors) allowed

• See Disease Characteristics

• At least 3 weeks since prior chemotherapy and recovered

• No prior irofulven

• No additional prior cytotoxic chemotherapy for recurrent or persistent disease, including retreatment with initial chemotherapy regimens

• At least 1 week since prior hormonal therapy for malignant tumor

• Concurrent hormone replacement therapy allowed

• See Disease Characteristics

• At least 3 weeks since prior radiotherapy and recovered

• No prior radiotherapy to more than 25% of marrow-bearing areas

• Recovered from recent prior surgery

• At least 3 weeks since any other prior therapy for malignant tumor

• No prior anticancer treatment that would preclude study therapy

• One prior noncytotoxic cytostatic regimen for recurrent or persistent disease allowed

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: Russell Schilder, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00053365
• Other Study ID Numbers: NCI-2012-02512; NCI-2012-02512; CDR0000269484; GOG-0146O; GOG-0146O; U10CA027469
• First Posted: Jan 28, 2003
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Carcinoma, Ovarian Epithelial; Recurrence; Irofulven

Study Results

Participant Flow

Recruitment Details	Stage I of the study accrued patients from 6/2/2003 through 10/31/2005. Stage II of the study accrued patients from 1/3/2006 through 4/7/2008.

Arm/Group Title	Treatment (Irofulven)
Arm/Group Description	Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
Period Title: Overall Study
STARTED	61
COMPLETED	55
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Treatment (Irofulven)
Arm/Group Description	Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
Overall Participants	55
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (9.7)
Age, Customized (participants) [Number]
30-39 years	1 1.8%
40-49 years	10 18.2%
50-59 years	17 30.9%
60-69 years	21 38.2%
70-79 years	4 7.3%
80-89 years	2 3.6%
Sex: Female, Male (Count of Participants)
Female	55 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	55 100%
Recurrent/Persistent Disease (participants) [Number]
Number [participants]	55 100%
Cell Type (participants) [Number]
Endometrioid Adenocarcinoma	2 3.6%
Mixed Epithelial Carcinoma	3 5.5%
Serous Adenocarcinoma	47 85.5%
Undifferentiated Carcinoma	3 5.5%

Outcome Measures

1. Primary Outcome

Title	Tumor Response
Description	Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria: Complete Response is disappearance of all target and non-target lesions; Partial Response is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable dimensions; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Response is to be evaluated every 42 days for the first 6 months and every 6 months thereafter while the patient is receiving study treatment, then every 3 months for 2 years and every 6 months for the next 3 years until documented progression or death.
Time Frame	From entry into study until documented progression or death, assessed up to 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Irofulven)
Arm/Group Description	Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
Measure Participants	55
Partial Response	7 12.7%
Stable Disease	30 54.5%
Increase Disease	12 21.8%
Indeterminate	6 10.9%

2. Primary Outcome

Title	Frequency and Severity of Observed Adverse Events, Grade 3 or Higher According to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment

Outcome Measure Data

Analysis Population Description

Eligible and evaluable patients

Arm/Group Title	Grade 3 (CTCAE v 2.0)	Grade 4 (CTCAE v 2.0)
Arm/Group Description	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	55	55
Leukopenia	11 20%	0 NaN
Thrombocytopenia	11 20%	2 NaN
Neutropenia	16 29.1%	6 NaN
Other hematologic	6 10.9%	0 NaN
Constitutional	4 7.3%	0 NaN
Gastrointestinal	8 14.5%	1 NaN
Infection	4 7.3%	0 NaN
Musculoskeletal	2 3.6%	0 NaN
Metabolic	2 3.6%	1 NaN
Neuropathy (sensory)	1 1.8%	0 NaN
Other neurologic	2 3.6%	0 NaN
Ocular	4 7.3%	0 NaN
Pain	1 1.8%	0 NaN

3. Secondary Outcome

Title	Progression-free Survival
Description	Per Gynecologic Oncology Group(GOG) Response Evaluation Criteria in Solid Tumors(RECIST) Criteria, progression is defined as at least a 20% increase in the sum of longest dimesions(LD) of target lesions taking as reference the smallest sum LD or the appearance of new lesions within 8 weeks of study entry.
Time Frame	From entry into study to death or date of last contact, assessed up to 5 years

Outcome Measure Data

Analysis Population Description

Eligible and evaluable

Arm/Group Title	Treatment (Irofulven)
Arm/Group Description	Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
Measure Participants	55
Median Overall Survival	24.1
Median Progression-free Survival	6.7

Adverse Events

Time Frame	Adverse Events(AEs) considered to be due to study treatment are to be reported up until 5 years after initiating treatment.
Adverse Event Reporting Description	A patient's AEs are reported following each cycle of study treatment and include AEs occurring within 30 days of each cycle.
Arm/Group Title	Treatment (Irofulven)
Arm/Group Description	Patients receive irofulven IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression.
All Cause Mortality
	Treatment (Irofulven)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Irofulven)
	Affected / at Risk (%)	# Events
Total	18/55 (32.7%)
Cardiac disorders
Cardiovascular Other	1/55 (1.8%)
Thrombosis Embolism	1/55 (1.8%)
Eye disorders
Ocular Other	1/55 (1.8%)
Vision Photophobia	2/55 (3.6%)
Vision Blurres	1/55 (1.8%)
Gastrointestinal disorders
Anorexia	2/55 (3.6%)
Ileus	1/55 (1.8%)
Constipation	1/55 (1.8%)
Dehydration	2/55 (3.6%)
Vomitting	3/55 (5.5%)
Gi Other	2/55 (3.6%)
Infections and infestations
Infection Without Neutropenia	2/55 (3.6%)
Metabolism and nutrition disorders
Hypomagnesmia	1/55 (1.8%)
Musculoskeletal and connective tissue disorders
Muscle Weakness	1/55 (1.8%)
Nervous system disorders
Ataxia(Incoordination)	3/55 (5.5%)
Neuropathy Sensor	1/55 (1.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/55 (1.8%)
Other (Not Including Serious) Adverse Events
	Treatment (Irofulven)
	Affected / at Risk (%)	# Events
Total	55/55 (100%)
Blood and lymphatic system disorders
Neutropenia	38/55 (69.1%)
Thrombocytopenia	41/55 (74.5%)
Lymphopenia	4/55 (7.3%)
Leukopenia	39/55 (70.9%)
Transfusion Prbc's	5/55 (9.1%)
Anemia	45/55 (81.8%)
Cardiac disorders
Sinus Tachycardia	3/55 (5.5%)
Edema	5/55 (9.1%)
Endocrine disorders
Hot Flashes/Flushes	7/55 (12.7%)
Eye disorders
Ocular Other	5/55 (9.1%)
Dry Eye	3/55 (5.5%)
Vision Photophobia	5/55 (9.1%)
Vision Flashing Lights/Floaters	9/55 (16.4%)
Vision Blurres	8/55 (14.5%)
Gastrointestinal disorders
Anorexia	12/55 (21.8%)
Flatulence	6/55 (10.9%)
Dyspepsia/Heartburn	10/55 (18.2%)
Dysphagia Esophagitis Odynophagia	4/55 (7.3%)
Diarrhea Without Colostomy	17/55 (30.9%)
Constipation	22/55 (40%)
Stomatitis/Pharyngitis	7/55 (12.7%)
Vomitting	22/55 (40%)
Nausea	38/55 (69.1%)
General disorders
Fever(No Neutropenia)	4/55 (7.3%)
Sweating	3/55 (5.5%)
Fatigue	41/55 (74.5%)
Abdominal Pain	18/55 (32.7%)
Pain Other	7/55 (12.7%)
Headache	17/55 (30.9%)
Arthralgia	3/55 (5.5%)
Myalgia	8/55 (14.5%)
Hepatobiliary disorders
Hypoalbuminemia	5/55 (9.1%)
Sgot(Alt)	7/55 (12.7%)
Sgot(Ast)	5/55 (9.1%)
Alkaline Phosphatase	6/55 (10.9%)
Infections and infestations
Infection Without Neutropenia	9/55 (16.4%)
Metabolism and nutrition disorders
Hyponatremia	3/55 (5.5%)
Hypocalcemia	5/55 (9.1%)
Hyperglycemia	8/55 (14.5%)
Hypokalemia	8/55 (14.5%)
Hypomagnesmia	10/55 (18.2%)
Musculoskeletal and connective tissue disorders
Muscle Weakness	3/55 (5.5%)
Nervous system disorders
Ataxia(Incoordination)	3/55 (5.5%)
Insomnia	6/55 (10.9%)
Dizziness	7/55 (12.7%)
Mood Alteration Depression	4/55 (7.3%)
Neuropathy Sensor	19/55 (34.5%)
Renal and urinary disorders
Urinary Retention	3/55 (5.5%)
Proteinuria	3/55 (5.5%)
Respiratory, thoracic and mediastinal disorders
Voice Changes/Stridor/Larynx	3/55 (5.5%)
Cough	4/55 (7.3%)
Dyspnea	7/55 (12.7%)
Skin and subcutaneous tissue disorders
Pruritis	3/55 (5.5%)
Alopecia	10/55 (18.2%)
Rash Desquamation	5/55 (9.1%)
Bruising	3/55 (5.5%)
Vascular disorders
Hematuria No Vaginal Bleeding	3/55 (5.5%)

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.