ABI-007 in Treating Patients With Persistent or Recurrent Cervical Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00309959
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 37
• Locations: 26
• Arm: 1
• Patients Per Site: 1.4

Study Details

Study Description

Brief Summary

This phase II trial is studying how well ABI-007 works in treating patients with persistent or recurrent cervical cancer. Drugs used in chemotherapy, such as ABI-007, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma	Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

OBJECTIVES:

1. Estimate the antitumor activity of ABI-007 in patients with persistent or recurrent squamous or nonsquamous cell carcinoma of the cervix who have failed on higher-priority treatment protocols.

2. Determine the nature and degree of toxicity of ABI-007 in this cohort of patients.

3. To determine the expression of the SPARC (secreted protein, acidic and rich in cysteine) protein in the tumor tissue and plasma (exploratory study) of patients treated with this regimen.

OUTLINE: This is an open-label, multicenter study.

Patients receive ABI-007 IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for SPARC protein expression analysis by ELISA. Archived tumor tissue samples are also analyzed.

After completion of study treatment, patients are followed periodically for up to 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Evaluation of ABI-007 in the Treatment of Persistent or Recurrent Squamous or Nonsquamous Cell Carcinoma of the Cervix
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (paclitaxel albumin-stabilized nanoparticle) Patients receive ABI-007 IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation; Given IV; Other Names: ABI 007 ABI-007 Abraxane ; Other: Laboratory Biomarker Analysis; Correlative studies

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; then every 3 months x 2; then every 6 months 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. Frequency and Severity of Observed Adverse Effects Assessed by Common Terminology Criteria for Adverse Events (CTCAE) [Up to 5 yearsAssessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Persistent or recurrent squamous or nonsquamous cell carcinoma of the cervix with documented disease progression

• Histologic confirmation of the original primary tumor

• Measurable disease, defined as at least one target lesion that can be accurately measured in at least one dimension ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT scan, or MRI, or ≥ 10 mm when measured by spiral CT scan

• Tumors within a previously irradiated field will be designated as nontarget lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days after completion of radiotherapy

• Must have received 1 prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent squamous or nonsquamous cell carcinoma of the cervix

• Chemotherapy administered as a radiosensitizer is not a systemic chemotherapy regimen

• Not eligible for a higher priority GOG protocol

• GOG performance status 0, 1, or 2

• No active infection requiring antibiotics

• Platelet count ≥ 100,000/mm^3

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

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

• Bilirubin ≤ 1.5 times ULN

• SGOT and alkaline phosphatase ≤ 2.5 times ULN

• No neuropathy (sensory and motor) > grade 1

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No evidence of any other invasive malignancies within the past 3-5 years, except localized breast cancer, head and neck cancer, cervical cancer, or nonmelanoma skin cancer

• No pre-existing hearing loss/tinnitus > grade 1

• No concurrent amifostine or other protective agents

• Recovered from effects of prior surgery, radiotherapy, or chemotherapy

• Hormonal therapy directed at malignant tumor must be discontinued at least 1 week prior to study entry

• Continuation of hormone replacement therapy permitted

• At least 3 weeks since prior biological therapy and immunotherapy

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

• May have received 1 additional noncytotoxic (biologic or cytostatic) regimen, including monoclonal antibodies, cytokines, or small-molecule inhibitors of signal transduction

• No prior radiotherapy to any portion of the abdominal cavity or pelvis

• Radiotherapy for the treatment of cervical cancer within the past 5 years allowed

• Radiotherapy for localized breast cancer, head and neck or skin allowed provided completion > 3 years prior to study entry and remains free of recurrent or metastatic disease

• No prior chemotherapy for any abdominal or pelvic tumor

• Chemotherapy for the treatment of cervical cancer within the past 5 years allowed

• Prior adjuvant chemotherapy for localized breast cancer provided completion > 3 years prior to study entry and remains free of recurrent or metastatic disease

• No prior therapy with ABI-007 or any other taxane

• No prior anticancer treatment that would preclude study therapy

• No concurrent ritonavir, saquinavir, indinavir, nelfinavir, or anticonvulsants

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
2	Rush University Medical Center	Chicago	Illinois	United States	60612
3	Carle Clinic-Urbana Main	Urbana	Illinois	United States	61801
4	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
5	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
6	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
7	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
8	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
9	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
10	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
11	Women's Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
12	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
13	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey	United States	08060
14	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey	United States	08043
15	Women's Cancer Care Associates LLC	Albany	New York	United States	12208
16	University of North Carolina	Chapel Hill	North Carolina	United States	27599
17	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
18	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
19	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
20	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
21	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
22	Lyndon Baines Johnson General Hospital	Houston	Texas	United States	77026-1967
23	M D Anderson Cancer Center	Houston	Texas	United States	77030
24	Carilion Clinic Gynecological Oncology	Roanoke	Virginia	United States	24016
25	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
26	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Gynecologic Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Alberts, Gynecologic Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT00309959
• Other Study ID Numbers: GOG-0127V; NCI-2009-00576; GOG-0127V; CDR0000463520; GOG-0127V; GOG-0127V; U10CA027469
• First Posted: Apr 3, 2006
• Last Update Posted: Jan 8, 2019
• Last Verified: Dec 1, 2014

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Small Cell; Small Cell Lung Carcinoma; Carcinoma, Adenosquamous; Recurrence; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	This trial was opened to patient entry on November 6, 2006 and was closed to accrual on February 1, 2011.

Arm/Group Title	ABI-007
Arm/Group Description	ABI-007 125 mg/m2 IV weekly on day 1, 8, and 15 every 28 days (one cycle) until disease progression or adverse effects prohibit further therapy
Period Title: Overall Study
STARTED	37
COMPLETED	35
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	ABI-007
Arm/Group Description	ABI-007 125 mg/m2 IV weekly on day 1, 8, and 15 every 28 days (one cycle) until disease progression or adverse effects prohibit further therapy
Overall Participants	35
Age, Customized (participants) [Number]
<40 years	6 17.1%
40-49 years	15 42.9%
50-59 years	10 28.6%
60-69 years	3 8.6%
>70 yeats	1 2.9%
Sex: Female, Male (Count of Participants)
Female	35 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2.9%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 8.6%
White	30 85.7%
More than one race	0 0%
Unknown or Not Reported	1 2.9%

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; then every 3 months x 2; then every 6 months until disease progression for up to 5 years.

Outcome Measure Data

Analysis Population Description

Eligible and treated patients

Arm/Group Title	ABI-007
Arm/Group Description	ABI-007 125 mg/m2 IV weekly on day 1, 8, and 15 every 28 days (one cycle) until disease progression or adverse effects prohibit further therapy
Measure Participants	35
Partial response	10 28.6%
Complete response	0 0%

2. Primary Outcome

Title	Frequency and Severity of Observed Adverse Effects Assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Time Frame	Up to 5 yearsAssessed 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

[Not Specified]

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	35	35	35	35	35
Leukopenia	11 31.4%	10 NaN	12 NaN	3 NaN	0 NaN
Thrombocytopenia	30 85.7%	4 NaN	0 NaN	1 NaN	0 NaN
Neutropenia	20 57.1%	6 NaN	6 NaN	1 NaN	2 NaN
Anemia	3 8.6%	6 NaN	22 NaN	4 NaN	0 NaN
Nausea/Vomiting	15 42.9%	11 NaN	9 NaN	0 NaN	0 NaN
Other gastrointestinal	13 37.1%	10 NaN	10 NaN	2 NaN	0 NaN
Genitourinary	34 97.1%	1 NaN	0 NaN	0 NaN	0 NaN
Neurotoxicity	15 42.9%	11 NaN	8 NaN	1 NaN	0 NaN
Pain	20 57.1%	9 NaN	4 NaN	2 NaN	0 NaN
Pulmonary	31 88.6%	1 NaN	2 NaN	2 NaN	0 NaN
Cardiovascular	34 97.1%	0 NaN	1 NaN	0 NaN	0 NaN
Fatigue	8 22.9%	7 NaN	15 NaN	5 NaN	0 NaN
Metabolic	24 68.6%	5 NaN	2 NaN	4 NaN	0 NaN
Dermatologic	30 85.7%	1 NaN	3 NaN	1 NaN	0 NaN
Alopecia	17 48.6%	3 NaN	15 NaN	0 NaN	0 NaN
Musculoskeletal	32 91.4%	2 NaN	1 NaN	0 NaN	0 NaN
Auditory	34 97.1%	0 NaN	1 NaN	0 NaN	0 NaN
Infection	27 77.1%	0 NaN	4 NaN	4 NaN	0 NaN
SGOT	34 97.1%	1 NaN	0 NaN	0 NaN	0 NaN
Alkaline phosphatase	34 97.1%	1 NaN	0 NaN	0 NaN	0 NaN
Lymphatics	31 88.6%	2 NaN	2 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	ABI-007
Arm/Group Description	ABI-007 125 mg/m2 IV weekly on day 1, 8, and 15 every 28 days (one cycle) until disease progression or adverse effects prohibit further therapy
All Cause Mortality
	ABI-007
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	ABI-007
	Affected / at Risk (%)	# Events
Total	17/35 (48.6%)
Blood and lymphatic system disorders
Edema: Limb	1/35 (2.9%)
Gastrointestinal disorders
Mucositis (Clinical Exam) - Oral Cavity	1/35 (2.9%)
Dehydration	1/35 (2.9%)
Prolapse Of Stoma, Gi	1/35 (2.9%)
General disorders
Fever	1/35 (2.9%)
Death No Ctcae Term - Death Nos	1/35 (2.9%)
Pain: Extremity-Limb	1/35 (2.9%)
Pain: Back	1/35 (2.9%)
Infections and infestations
Infection with Normal Or Grade 1 Or 2 Absolute Neutrophil Count: Blood	1/35 (2.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Wound	1/35 (2.9%)
Inf W/Nml Or Gr 1 Or 2 Anc: Urinary Tract Nos	1/35 (2.9%)
Metabolism and nutrition disorders
Creatinine	2/35 (5.7%)
Musculoskeletal and connective tissue disorders
Gait/Walking	1/35 (2.9%)
Nervous system disorders
Neurology - Other	1/35 (2.9%)
Renal and urinary disorders
Cystitis	1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/35 (5.7%)
Vascular disorders
Hemorrhage, Gi - Rectum	1/35 (2.9%)
Other (Not Including Serious) Adverse Events
	ABI-007
	Affected / at Risk (%)	# Events
Total	34/35 (97.1%)
Blood and lymphatic system disorders
Leukopenia	25/35 (71.4%)
Thrombocytopenia	5/35 (14.3%)
Neutropenia	15/35 (42.9%)
Anemia	32/35 (91.4%)
Lymphatics	4/35 (11.4%)
Cardiac disorders
Cardiovascular	1/35 (2.9%)
Ear and labyrinth disorders
Auditory	1/35 (2.9%)
Gastrointestinal disorders
Nausea/vomiting	20/35 (57.1%)
Other gastrointestinal	22/35 (62.9%)
General disorders
Pain	15/35 (42.9%)
Constitutional (Fatigue)	27/35 (77.1%)
Infections and infestations
Infection	8/35 (22.9%)
Investigations
SGOT	1/35 (2.9%)
Alkaline phosphatase	1/35 (2.9%)
Metabolism and nutrition disorders
Metabolic	11/35 (31.4%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	3/35 (8.6%)
Nervous system disorders
Neurotoxicity	20/35 (57.1%)
Renal and urinary disorders
GU	1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Pulmonary	5/35 (14.3%)
Skin and subcutaneous tissue disorders
Dermatologic	5/35 (14.3%)
Alopecia	18/35 (51.4%)

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.