Oxaliplatin and Paclitaxel in Treating Patients With Locally Recurrent or Metastatic Cervical Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00057863
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Duration (Months): 85.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of combining oxaliplatin with paclitaxel in treating patients who have locally recurrent or metastatic cervical cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer	Drug: Paclitaxel; Drug: Oxaliplatin	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the objective response rates for the combination of paclitaxel and oxaliplatin in patients with metastatic or locally recurrent cervical cancer.

2. To determine the toxicities and recovery from toxicities of patients with cervical cancer receiving paclitaxel and oxaliplatin.

OUTLINE:

Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed ever 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Oxaliplatin in Combination With Paclitaxel in Patients With Locally Recurrent or Metastatic Cervical Cancer
• Study Start Date: Jan 1, 2003
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (paclitaxel, oxaliplatin) Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Paclitaxel; Given IV; Other Names: Anzatax TAX ; Drug: Oxaliplatin; Given IV

Outcome Measures

Primary Outcome Measures

1. Overall Objective Response Rate (CR+PR) [Up to 7 years]

   95% confidence interval will be estimated via binomial proportions.

Secondary Outcome Measures

1. Progression-free Survival [From first treatment day until objective or symptomatic progression or death, assessed up to 7 years]

   Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

2. Overall Survival [From first treatment day until death, assessed up to 7 years]

   Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.

3. Toxicities, Assessed and Graded According to CTCAE Version 3.0 [Up to 7 years]

   Exact 95% confidence intervals will be calculated. The 95% confidence interval was not calculated for the toxicities

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed squamous cell, adenosquamous cell or adenocarcinoma of the uterine cervix

• Lesions must be metastatic to organs or lymph nodes outside the pelvis or must be locally recurrent in the pelvis after definitive therapy (surgery or radiation therapy) with at least 50% increase in size on sequential imaging studies

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

• Patients may have received chemotherapy in conjunction with radiation therapy for primary, definitive therapy; patients may not have received treatment with cytotoxic agents for advanced or recurrent disease

• Patients who have had chemotherapy, radiation therapy or surgery must allow four weeks for recovery of bone marrow or recovery from surgery/radiation

• Life expectancy of greater than 2 months

• ECOG performance status =< 2 (Karnofsky >= 60%)

• Leukocytes >= 3,000/uL

• Absolute neutrophil count >= 1,500/uL

• Platelets >= 100,000/uL

• Total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

• Creatinine within normal institutional limits

• The effects of oxaliplatin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Patients may not be receiving any other investigational agents

• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, cisplatin or carboplatin or paclitaxel or docetaxel

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study because oxaliplatin is a platinating agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin and paclitaxel, breastfeeding should be discontinued if the mother is treated with oxaliplatin

• Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with oxaliplatin or other agents administered during the study; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dennis Kuo, Montefiore Medical Center - Moses Campus

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00057863
• Other Study ID Numbers: NCI-2012-03004; NCI-2012-03004; NCI-5840; 0902-492; 5840; N01CM62204; P30CA013330
• First Posted: Apr 9, 2003
• Last Update Posted: Nov 17, 2015
• Last Verified: Dec 1, 2012

• Additional relevant MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Carcinoma, Adenosquamous; Recurrence; Paclitaxel; Oxaliplatin

Study Results

Participant Flow

Recruitment Details	A total of 35 patients were enrolled in the study from April 2003 until August 2008.

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
Period Title: Overall Study
STARTED	35
COMPLETED	32
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
Overall Participants	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	32 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
White	12 37.5%
Hispanic	9 28.1%
Black	8 25%
Asian	3 9.4%

Outcome Measures

1. Primary Outcome

Title	Overall Objective Response Rate (CR+PR)
Description	95% confidence interval will be estimated via binomial proportions.
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
Measure Participants	32
Complete Response	2 6.3%
Partial Respone	5 15.6%
Stable disease	8 25%

2. Secondary Outcome

Title	Progression-free Survival
Description	Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
Time Frame	From first treatment day until objective or symptomatic progression or death, assessed up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
Measure Participants	32
Mean (95% Confidence Interval) [weeks]	21

3. Secondary Outcome

Title	Overall Survival
Description	Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formulae.
Time Frame	From first treatment day until death, assessed up to 7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
Measure Participants	32
Mean (95% Confidence Interval) [weeks]	52

4. Secondary Outcome

Title	Toxicities, Assessed and Graded According to CTCAE Version 3.0
Description	Exact 95% confidence intervals will be calculated. The 95% confidence interval was not calculated for the toxicities
Time Frame	Up to 7 years

Outcome Measure Data

Analysis Population Description

There were 135 cycles administered.

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
Measure Participants	32
grade 3/4 hematologic toxicities	20.1
grade 3/4 non-hematologic toxicities	34.1

Adverse Events

Arm/Group Title	Treatment (Paclitaxel, Oxaliplatin)
Arm/Group Description	Patients receive paclitaxel IV over 3 hours and oxaliplatin IV over 2 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Paclitaxel: Given IV Oxaliplatin: Given IV
All Cause Mortality
	Treatment (Paclitaxel, Oxaliplatin)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Paclitaxel, Oxaliplatin)
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Blood and lymphatic system disorders
Neutropenia	8/32 (25%)	8
Febrile neutropenia	1/32 (3.1%)	1
Anemia	12/32 (37.5%)	12
Thrombocytopenia	4/32 (12.5%)	4
Gastrointestinal disorders
Nausea	1/32 (3.1%)	1
Vomiting	1/32 (3.1%)	1
Diarrhea	1/32 (3.1%)	1
Constipation	1/32 (3.1%)	1
Colitis	1/32 (3.1%)	1
Bowel perforation fistula	3/32 (9.4%)	3
Dehydration	1/32 (3.1%)	1
General disorders
Pain	8/32 (25%)	8
Weakness	5/32 (15.6%)	5
Death NOS	2/32 (6.3%)	2
Infections and infestations
Infection	2/32 (6.3%)	2
Investigations
Coagulopathy	1/32 (3.1%)	1
Metabolism and nutrition disorders
Electrolytes imbalance	14/32 (43.8%)	14
Nervous system disorders
Neuropathy	5/32 (15.6%)	5
Psychiatric disorders
Psychological	1/32 (3.1%)	1
Reproductive system and breast disorders
Severe vaginal hemorrhage	1/32 (3.1%)	1
Skin and subcutaneous tissue disorders
Hypersensitivity reaction	1/32 (3.1%)	1
Vascular disorders
Thrombosis	2/32 (6.3%)	2
Other (Not Including Serious) Adverse Events
	Treatment (Paclitaxel, Oxaliplatin)
	Affected / at Risk (%)	# Events
Total	32/32 (100%)
Gastrointestinal disorders
Pain: Abdomen	2/32 (6.3%)	2
General disorders
Fatigue	9/32 (28.1%)	9
Edema:limb	3/32 (9.4%)	3
Fever	3/32 (9.4%)	3
Investigations
Leukocytes	5/32 (15.6%)	5
Metabolism and nutrition disorders
Aspartate aminotransferase increased	2/32 (6.3%)	2
Alkaline phosphatase	2/32 (6.3%)	2
Musculoskeletal and connective tissue disorders
Pain: Muscle	4/32 (12.5%)	4
Pain: back	2/32 (6.3%)	2
Pain: Bone	2/32 (6.3%)	2
Pain: Joint	2/32 (6.3%)	2
Nervous system disorders
Ataxia	2/32 (6.3%)	2
Psychiatric disorders
Insomnia	2/32 (6.3%)	2
Skin and subcutaneous tissue disorders
Alopecia	8/32 (25%)	8

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.