Study of Gemcitabine and Concurrent Radiation Followed by Adjuvant Hysterectomy in Bulky Stage Ib and IIa Cervical Carcinoma

• Sponsor: University of Southern California (Other)
• Overall Status: Completed
• CT.gov ID: NCT00184093
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arm: 1
• Duration (Months): 119
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is first to establish what is the ideal dose of gemcitabine, a chemotherapy agent, when given in combination with radiation. In addition, the investigators want to determine the side effects and the effectiveness of this combination. The investigators will also study several markers to try to identify markers or tests that will predict which patients will benefit more from this treatment.

Condition or Disease	Intervention/Treatment	Phase
Uterine Cervical Cancer	Drug: Gemcitabine	Phase 1/Phase 2

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: Phase I/II Study of Gemcitabine and Concurrent Radiation Followed by Adjuvant Hysterectomy in Bulky Stage Ib and IIa Cervical Carcinoma: Analysis of Prognostic Factors and Determinants of Response: A Pilot Study
• Study Start Date: Jun 1, 1999
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine weekly x 6 wks with concurrent external radiation Gemcitabine 350 mg/m2 IV weekly x 6 weeks with concurrent external radiation	Drug: Gemcitabine; Gemcitabine weekly x 6 wks with concurrent external radiation

Outcome Measures

Primary Outcome Measures

1. Toxicity (Number of Participants With Serious Adverse Events) [Every 3 weeks from start of study until 30 days after the last dose of treatment]

   Summary of grade 3 or higher toxicities as per Common Toxicity Criteria version 2.0. Phase 1 and 2 Combined (N=35)

Secondary Outcome Measures

1. Best Overall Response of Either a Complete Response (CR) or Partial Response (PR) [Baseline to response (up to 24 months)]

   Participants who complete the 6 weeks of chemotherapy and radiation or who experience dose limiting toxicity or who progress at any time prior to completion of the 6 weeks of chemotherapy and radiation will be evaluable for response. Complete response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No disease related symptoms. No evidence of nonevaluable disease, including normalization of markers and other abnormal lab values. All measurable, evaluable, and nonevaluable lesions and sites must be assessed using the same technique as baseline. Partial response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients with histologically confirmed bulky stage Ib or stage IIa cervical cancer. Bulky stage Ib disease is defined as tumor mass greater than 4 cms in diameter.

• Cervical lesion which is measurable by physical examination.

• No prior therapy for invasive cervical cancer.

• GOG performance status 0-2

• Signed informed consent

• Patients must have adequate:

• Bone marrow function: absolute granulocyte count > or = to 1500, platelet count > 100,000.

• Renal function: creatinine < or = to 1.8 mg/dl

• Hepatic function: bilirubin < or = to 1.5 x normal, SGOT and alkaline phosphatase < or = to 3 x normal

Exclusion Criteria:

• Patients with a history of prior malignancy, except adequately treated basal cell or squamous cell carcinoma of the skin, or other cancer for which the patient has been disease free for at least five years.

• Pregnant or lactating women. Women of reproductive age may not participate unless they have agreed to use an effective method of birth control.

• Patients with uncontrolled infection.

• Patients who are HIV positive

• Patients with psychiatric or social conditions that would interfere with consent or follow-up.

• Patients with any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033

Sponsors and Collaborators

• University of Southern California

Investigators

• Principal Investigator: Lynda Roman, MD, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Southern California
• ClinicalTrials.gov Identifier: NCT00184093
• Other Study ID Numbers: 5C-99-1
• First Posted: Sep 16, 2005
• Last Update Posted: Aug 15, 2017
• Last Verified: Jul 1, 2017

• Keywords provided by University of Southern California: Cervical Carcinoma
• Additional relevant MeSH terms: Carcinoma; Uterine Cervical Neoplasms; Gemcitabine

Study Results

Participant Flow

Recruitment Details	The study began recruiting in July 1999 and recruitment ended in May 2008. All participants were seen and treated at USC Norris Comprehensive Cancer Center and/or at LAC+USC Medical Center.
Pre-assignment Detail	The study had no pre-assignment criteria. This was an open label study and all participants were given the same treatment.

Arm/Group Title	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
Arm/Group Description	Gemcitabine 350 mg/m2 IV weekly x 6 weeks with concurrent external radiation Gemcitabine: Gemcitabine weekly x 6 wks with concurrent external radiation
Period Title: Overall Study
STARTED	35
COMPLETED	26
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
Arm/Group Description	Gemcitabine 350 mg/m2 IV weekly x 6 weeks with concurrent external radiation Gemcitabine: Gemcitabine weekly x 6 wks with concurrent external radiation
Overall Participants	35
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	35 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	35 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	33 94.3%
Not Hispanic or Latino	2 5.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 5.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	33 94.3%
Region of Enrollment (participants) [Number]
United States	35 100%

Outcome Measures

1. Primary Outcome

Title	Toxicity (Number of Participants With Serious Adverse Events)
Description	Summary of grade 3 or higher toxicities as per Common Toxicity Criteria version 2.0. Phase 1 and 2 Combined (N=35)
Time Frame	Every 3 weeks from start of study until 30 days after the last dose of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
Arm/Group Description	Gemcitabine 350 mg/m2 IV weekly x 6 weeks with concurrent external radiation Gemcitabine: Gemcitabine weekly x 6 wks with concurrent external radiation
Measure Participants	35
Count of Participants [Participants]	10 28.6%

2. Secondary Outcome

Title	Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)
Description	Participants who complete the 6 weeks of chemotherapy and radiation or who experience dose limiting toxicity or who progress at any time prior to completion of the 6 weeks of chemotherapy and radiation will be evaluable for response. Complete response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No disease related symptoms. No evidence of nonevaluable disease, including normalization of markers and other abnormal lab values. All measurable, evaluable, and nonevaluable lesions and sites must be assessed using the same technique as baseline. Partial response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline.
Time Frame	Baseline to response (up to 24 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
Arm/Group Description	Gemcitabine 350 mg/m2 IV weekly x 6 weeks with concurrent external radiation Gemcitabine: Gemcitabine weekly x 6 wks with concurrent external radiation
Measure Participants	35
Count of Participants [Participants]	32 91.4%

Adverse Events

Time Frame	Adverse events were collected beginning cycle 1 and continued throughout the study until 30 days after the last dose.
Arm/Group Title	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
Arm/Group Description	Gemcitabine 350 mg/m2 IV weekly x 6 weeks with concurrent external radiation Gemcitabine: Gemcitabine weekly x 6 wks with concurrent external radiation
All Cause Mortality
	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
	Affected / at Risk (%)	# Events
Total	0/35 (0%)
Serious Adverse Events
	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
	Affected / at Risk (%)	# Events
Total	10/35 (28.6%)
Blood and lymphatic system disorders
Hemoglobin	2/35 (5.7%)	2
Leukocytes (total WBC)	6/35 (17.1%)	6
Lymphopenia	2/35 (5.7%)	2
Neutrophils/granulocytes (ANC/AGC)	5/35 (14.3%)	5
Gastrointestinal disorders
Anorexia	1/35 (2.9%)	1
Dehydration	1/35 (2.9%)	1
Diarrhea patients without colostomy	10/35 (28.6%)	14
Nausea	2/35 (5.7%)	2
Proctitis	2/35 (5.7%)	2
Rectal bleeding/hematochezia	1/35 (2.9%)	1
Vomiting	4/35 (11.4%)	4
General disorders
Rectal or perirectal pain (proctalgia)	1/35 (2.9%)	1
Hepatobiliary disorders
Alkaline phosphatase	1/35 (2.9%)	1
SGOT (AST) (serum glutamic oxaloacetic transaminase)	2/35 (5.7%)	2
SGPT (ALT) (serum glutamic pyruvic transaminase)	5/35 (14.3%)	6
Metabolism and nutrition disorders
Hyperglycemia	1/35 (2.9%)	3
Reproductive system and breast disorders
Vaginal bleeding	2/35 (5.7%)	2
Other (Not Including Serious) Adverse Events
	Gemcitabine Weekly x 6 Wks With Concurrent External Radiation
	Affected / at Risk (%)	# Events
Total	33/35 (94.3%)
Blood and lymphatic system disorders
Hemoglobin	24/35 (68.6%)	50
Leukocytes (total WBC)	22/35 (62.9%)	39
Lymphopenia	2/35 (5.7%)	5
Neutrophils/granulocytes (ANC/AGC)	23/35 (65.7%)	38
Platelets	11/35 (31.4%)	13
Cardiac disorders
Hypotension	1/35 (2.9%)	1
Sinus tachycardia	2/35 (5.7%)	2
Ear and labyrinth disorders
Auditory/Hearing-Other (not specified)	5/35 (14.3%)	5
Inner ear/hearing	5/35 (14.3%)	11
Middle ear/hearing	1/35 (2.9%)	1
Endocrine disorders
Hot flashes/flushes	3/35 (8.6%)	4
Gastrointestinal disorders
Abdominal pain or cramping	17/35 (48.6%)	25
Anorexia	27/35 (77.1%)	44
Constipation	24/35 (68.6%)	35
Diarrhea patients without colostomy	33/35 (94.3%)	67
Melena/GI bleeding	1/35 (2.9%)	1
Proctitis	11/35 (31.4%)	12
Rectal bleeding/hematochezia	11/35 (31.4%)	12
Stomatitis/pharyngitis (ora/pharyngeal mucositis)	5/35 (14.3%)	6
Vomiting	21/35 (60%)	41
General disorders
Constitutional Symptoms-Other (not specified)	7/35 (20%)	8
Edema	6/35 (17.1%)	9
Fatigue (lethargy, malaise, asthenia)	23/35 (65.7%)	51
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	5/35 (14.3%)	6
Nausea	31/35 (88.6%)	70
Pain	10/35 (28.6%)	12
Pain-Other (specify, pelvic)	9/35 (25.7%)	11
Rectal or perirectal pain (proctalgia)	6/35 (17.1%)	9
Rigors, chills	27/35 (77.1%)	46
Hepatobiliary disorders
Alkaline phosphatase	12/35 (34.3%)	16
Hypoalbuminemia	2/35 (5.7%)	2
SGOT (AST) (serum glutamic oxaloacetic transaminase)	17/35 (48.6%)	25
SGPT (ALT) (serum glutamic pyruvic transaminase)	21/35 (60%)	34
Infections and infestations
Infection without neutropenia	10/35 (28.6%)	10
Injury, poisoning and procedural complications
Radiation Dermatitis	6/35 (17.1%)	8
Metabolism and nutrition disorders
Hyperglycemia	7/35 (20%)	8
Hypocalcemia	1/35 (2.9%)	1
Hyponatremia	1/35 (2.9%)	1
Musculoskeletal and connective tissue disorders
Arthralgia (joint pain)	4/35 (11.4%)	5
Myalgia	1/35 (2.9%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain (onset or exacerbation of tumor pain due to treatment)	1/35 (2.9%)	2
Nervous system disorders
Dizziness/lightheadedness	15/35 (42.9%)	23
Headache	22/35 (62.9%)	36
Neuropathy-sensory	10/35 (28.6%)	11
Psychiatric disorders
Insomnia	2/35 (5.7%)	2
Mood alteration-anxiety, agitation	9/35 (25.7%)	12
Renal and urinary disorders
Creatinine	1/35 (2.9%)	1
Dysuria (painful urination)	28/35 (80%)	44
Hematuria (in the absence of vaginal bleeding)	1/35 (2.9%)	1
Reproductive system and breast disorders
Vaginal bleeding	20/35 (57.1%)	34
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1/35 (2.9%)	1
Cough	7/35 (20%)	12
Dyspnea (shortness of breath)	4/35 (11.4%)	4
Skin and subcutaneous tissue disorders
Alopecia	8/35 (22.9%)	8
Pigmentation changes (e.g., vitiligo)	3/35 (8.6%)	3
Pruritus	4/35 (11.4%)	4
Rash/desquamation	10/35 (28.6%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.