Topotecan in Treating Women With Persistent or Recurrent Cervical Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00087126
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 27
• Locations: 27
• Arm: 1
• Patient Per Site: 1

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well topotecan works in treating women with persistent or recurrent cervical cancer.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: topotecan hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

• Determine the antitumor activity of topotecan in patients with persistent or recurrent carcinoma of the cervix that failed higher priority treatment protocols.

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

OUTLINE: This is a multicenter study.

Patients receive topotecan IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 22-60 patients will be accrued for this study within 1-2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of Weekly Topotecan Hydrochloride (Hycamtin®, NSC #609699) in the Treatment of Persistent or Recurrent Carcinoma of the Cervix
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topotecan Topotecan weekly	Drug: topotecan hydrochloride

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0 [CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; every 6 months thereafter until disease progression for up to 5 years.]

   RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.

2. Number of Participants With Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 [Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up]

   All participants assessed by CTCAE v3 (Common Terminology Criteria for Adverse Events version 3.0) including grade 0 (the number of participants not affected by the Adverse Event).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the cervix

• Squamous cell or nonsquamous cell

• Persistent or recurrent disease

• Documented disease progression

• Measurable disease

• At least 1 unidimensionally measurable target lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Tumors within a previously irradiated field are considered non-target lesions unless disease progression is documented or a biopsy is obtained to confirm persistent disease at least 90 days after completion of prior radiotherapy

• Must have received 1 prior systemic chemotherapy regimen for persistent or recurrent squamous cell or nonsquamous cell carcinoma of the cervix

• Chemotherapy administered with primary radiotherapy as a radiosensitizer is not considered a systemic chemotherapy regimen

• Not eligible for a higher priority GOG protocol (i.e., any active phase III GOG protocol for the same patient population)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• GOG 0-2

Life expectancy

• Not specified

Hematopoietic

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

• Platelet count ≥ 100,000/mm^3

Hepatic

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

• SGOT ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Other

• Sensory or motor neuropathy ≤ grade 1

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No active infection requiring antibiotics

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• One prior non-cytotoxic (biologic or cytostatic) regimen for recurrent or persistent disease allowed, including, but not limited to, the following:

• Monoclonal antibodies

• Cytokines

• Small-molecule inhibitors of signal transduction

• At least 3 weeks since prior biologic or immunologic agents for cervical cancer

• No concurrent prophylactic growth factors, including filgrastim (G-CSF), sargramostim (GM-CSF), or pegfilgrastim

• No concurrent prophylactic thrombopoietic agents

Chemotherapy

• See Disease Characteristics

• Recovered from prior chemotherapy

• No more than 1 prior cytotoxic chemotherapy regimen (either with single or combination cytotoxic drug therapy)

• No prior topotecan

Endocrine therapy

• At least 1 week since prior hormonal therapy for cervical cancer

• Concurrent hormone replacement therapy allowed

Radiotherapy

• See Disease Characteristics

• Recovered from prior radiotherapy

Surgery

• Recovered from prior surgery

Other

• At least 3 weeks since other prior therapy for cervical cancer

• No prior cancer therapy that would preclude study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama	United States	35294
2	Kaiser Permanente Medical Center - Los Angeles	Los Angeles	California	United States	90027
3	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
4	Olive View - UCLA Medical Center Foundation	Sylmar	California	United States	91342
5	Helen and Harry Gray Cancer Center at Hartford Hospital	Hartford	Connecticut	United States	06102-5037
6	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut	United States	06050
7	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
8	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
9	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
10	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
11	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
12	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
13	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
14	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
15	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216
16	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
17	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
18	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
19	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
20	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
21	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210-1240
22	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
23	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
24	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
25	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
26	Cancer Care Associates - Midtown Tulsa	Tulsa	Oklahoma	United States	74104
27	Women and Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: James V. Fiorica, MD, Sarasota Memorial Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00087126
• Other Study ID Numbers: GOG-0127U; GOG-0127U; CDR0000372930
• First Posted: Jul 12, 2004
• Last Update Posted: Jan 8, 2019
• Last Verified: May 1, 2015

• Keywords provided by Gynecologic Oncology Group: recurrent cervical cancer; cervical squamous cell carcinoma
• Additional relevant MeSH terms: Uterine Cervical Neoplasms; Topotecan

Study Results

Participant Flow

Recruitment Details	This trial was opened to patient entry on January 3, 2005 and was closed to accrual on October 29, 2007.

Arm/Group Title	Topotecan Hydrochloride
Arm/Group Description	Topotecan hydrochloride 3.0 mg/m² IV over 30 minutes every 7 days for 21 days; 7 days off (cycle = 28 days)
Period Title: Overall Study
STARTED	27
COMPLETED	25
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Topotecan Hydrochloride
Arm/Group Description	Topotecan hydrochloride 3.0 mg/m² IV over 30 minutes every 7 days for 21 days; 7 days off (cycle = 28 days)
Overall Participants	25
Age, Customized (participants) [Number]
<40 years	4 16%
40-49 years	10 40%
50-59 years	8 32%
60-69 years	3 12%
Sex: Female, Male (Count of Participants)
Female	25 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 20%
White	18 72%
More than one race	0 0%
Unknown or Not Reported	1 4%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Objective Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) Using RECIST Version 1.0
Description	RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
Time Frame	CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; every 6 months thereafter until disease progression for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients with sufficient follow-up assessments to evaluate response

Arm/Group Title	Topotecan Hydrochloride
Arm/Group Description	Topotecan hydrochloride 3.0 mg/m² IV over 30 minutes every 7 days for 21 days; 7 days off (cycle = 28 days)
Measure Participants	22
Partial response	0 0%
Complete response	0 0%

2. Primary Outcome

Title	Number of Participants With Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Description	All participants assessed by CTCAE v3 (Common Terminology Criteria for Adverse Events version 3.0) including grade 0 (the number of participants not affected by the Adverse Event).
Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	Grade 0	Grade 1 (CTCAE v 3.0)	Grade 2 (CTCAE v 3.0)	Grade 3 (CTCAE v 3.0)	Grade 4 (CTCAE v 3.0)
Arm/Group Description	Number of patients who did not experience the specified AE.	Number of patients who experienced a grade 1 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).	Number of patients who experienced a grade 2 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).	Number of patients who experienced a grade 3 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).	Number of patients who experienced a grade 4 event using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).
Measure Participants	25	25	25	25	25
Leukopenia	6 24%	4 NaN	9 NaN	5 NaN	1 NaN
Thrombocytopenia	16 64%	4 NaN	3 NaN	0 NaN	2 NaN
Neutropenia	9 36%	8 NaN	4 NaN	2 NaN	2 NaN
Transfusions	24 96%	0 NaN	0 NaN	1 NaN	0 NaN
Anemia	1 4%	4 NaN	12 NaN	7 NaN	1 NaN
Hemorrhage	24 96%	1 NaN	0 NaN	0 NaN	0 NaN
Nausea/Vomiting	13 52%	7 NaN	4 NaN	1 NaN	0 NaN
Other gastrointestinal	12 48%	4 NaN	6 NaN	3 NaN	0 NaN
Genito urinary	22 88%	2 NaN	1 NaN	0 NaN	0 NaN
Neurotoxicity	19 76%	3 NaN	2 NaN	0 NaN	1 NaN
Pain	19 76%	4 NaN	1 NaN	0 NaN	1 NaN
Pulmonary	24 96%	0 NaN	0 NaN	1 NaN	0 NaN
Infection	22 88%	0 NaN	0 NaN	3 NaN	0 NaN
Constitutional	8 32%	5 NaN	7 NaN	3 NaN	2 NaN
Metabolic	22 88%	2 NaN	1 NaN	0 NaN	0 NaN
Dermatologic	22 88%	3 NaN	0 NaN	0 NaN	0 NaN
Alopecia	17 68%	7 NaN	1 NaN	0 NaN	0 NaN
Renal	21 84%	3 NaN	1 NaN	0 NaN	0 NaN
Alkaline Phosphatase	23 92%	2 NaN	0 NaN	0 NaN	0 NaN
Vascular	24 96%	0 NaN	0 NaN	1 NaN	0 NaN
Lymphatics	24 96%	0 NaN	0 NaN	1 NaN	0 NaN
Lymphopenia	24 96%	0 NaN	1 NaN	0 NaN	0 NaN

Adverse Events

Time Frame	Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
Arm/Group Title	Topotecan Hydrochloride
Arm/Group Description	Topotecan hydrochloride 3.0 mg/m² IV over 30 minutes every 7 days for 21 days; 7 days off (cycle = 28 days)
All Cause Mortality
	Topotecan Hydrochloride
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Topotecan Hydrochloride
	Affected / at Risk (%)	# Events
Total	9/25 (36%)
Eye disorders
Diplopia	1/25 (4%)
General disorders
Fatigue	1/25 (4%)
Death No Ctcae Term - Death Nos (Not Otherwise Specified)	1/25 (4%)
Pain: Extremity-Limb	1/25 (4%)
Pain: Back	1/25 (4%)
Infections and infestations
Infection with Normal Or Grade 1 Or 2 Absolute Neutrophil Count: Lung (Pneumonia)	1/25 (4%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/25 (4%)
Nervous system disorders
Central nervous system ischemia	1/25 (4%)
Renal and urinary disorders
Stricture, Anastomotic, Genitourinary - Ureter	1/25 (4%)
Vascular disorders
Thrombosis/Thrombus/Embolism	2/25 (8%)
Other (Not Including Serious) Adverse Events
	Topotecan Hydrochloride
	Affected / at Risk (%)	# Events
Total	25/25 (100%)
Blood and lymphatic system disorders
Leukopenia	19/25 (76%)
Thrombocytopenia	9/25 (36%)
Neutropenia	16/25 (64%)
Transfusions	1/25 (4%)
Anemia	24/25 (96%)
Lymphatics	1/25 (4%)
Lymphopenia	1/25 (4%)
Gastrointestinal disorders
Nausea/Vomiting	12/25 (48%)
Other gastrointestinal	13/25 (52%)
General disorders
Pain	6/25 (24%)
Constitutional	17/25 (68%)
Infections and infestations
Infection	3/25 (12%)
Investigations
Alkaline phosphatase	2/25 (8%)
Metabolism and nutrition disorders
Metabolic	3/25 (12%)
Nervous system disorders
Neurotoxicity	6/25 (24%)
Renal and urinary disorders
Genito urinary	3/25 (12%)
Renal	4/25 (16%)
Respiratory, thoracic and mediastinal disorders
Pulmonary	1/25 (4%)
Skin and subcutaneous tissue disorders
Dermatologic	3/25 (12%)
Alopecia	8/25 (32%)
Vascular disorders
Hemorrhage	1/25 (4%)
Vascular	1/25 (4%)

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.