Cervical Squamous Cell Carcinoma, Recurrent Cervical Carcinoma
Conditions
Brief summary
This phase II trial is studying cetuximab to see how well it works in treating patients with persistent or recurrent cervical cancer. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
Detailed description
PRIMARY OBJECTIVES: I. To assess the activity of cetuximab for patients with persistent or recurrent carcinoma of the cervix. II. To determine the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response. SECONDARY OBJECTIVES: I. To characterize the distribution of progression-free survival and overall survival. II. To determine the effect of cetuximab on the duration of objective response in persistent or recurrent carcinoma of the cervix. III. To determine the nature and degree of toxicity of cetuximab as assessed by CTCAE v3.0 in this cohort of patients. OUTLINE: Patients receive cetuximab IV over 120 minutes on day 1. Courses repeat once weekly in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed (with physical exams and histories) every three months for the first two years and then every six months for the next three years.
Interventions
BIOLOGICALCetuximab
Given IV
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria: * Patients must have persistent or recurrent squamous or non-squamous cell carcinoma of the cervix with documented disease progression (disease not amenable to curative therapy) * Histologic documentation of the original primary tumor is required via the pathology report * All patients must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded) * Each lesion must be ≥ 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT scan, and MRI, OR ≥ 10 mm when measured by spiral CT scan * Patients must have at least one target lesion to be used to assess response on this protocol * 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 following completion of radiation therapy * Patients must have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent carcinoma of the cervix * Chemotherapy administered in conjunction with primary radiation as a radiosensitizer is not counted as a systemic chemotherapy regimen * Patients must not be eligible for a higher priority GOG protocol, if one exists * In general, this would refer to any active GOG phase III protocol for the same patient population *
Exclusion criteria
* Patients with craniospinal metastases * Inclusion criteria: * Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2 or patients who have received two prior regimens must have a GOG performance status of 0 or 1 * Patients should be free of active infection requiring antibiotics * Platelet count ≥ 100,000/μl * ANC ≥ 1,500/μl * Creatinine ≤ 1.5 x institutional upper limit normal (ULN) * Bilirubin ≤ 1.5 x ULN * SGOT and alkaline phosphatase ≤ 2.5 x ULN * Neuropathy (sensory and motor) ≤ CTCAE v3.0 grade 1 * Calcium \< 11.0 mg/dL * Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiating protocol therapy and be practicing an effective form of contraception during protocol therapy and for at least two months following completion of protocol therapy *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Greater Than 6 Months | At 6 months | — |
| Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | every other cycle for the first 6 months; then every 3 months x 2; then every 6 months | Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0): Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response (PR) is 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. Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease. |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Progression-free Survival | From study entry until disease progression, death or date of last contact, up to 5 years |
| Duration of Objective Response Rate | Up to 5 years |
| Frequency and Severity of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 | Up to 5 years |
| Duration of Overall Survival | From study entry to death or the date of last contact, up to 5 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Cetuximab) Day 1: 400 mg/m2 loading dose of cetuximab IV over 120 minutes; Day 8 and weekly thereafter: 250 mg/m2 cetuximab IV over 60 minutes (one cycle = four weeks) until disease progression or adverse effects prohibit further therapy | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Improper pre-protocol treatment | 1 |
| Overall Study | Never treated | 1 |
| Overall Study | Required test not done | 1 |
Baseline characteristics
| Characteristic | Treatment (Cetuximab) |
|---|---|
| Age, Customized 30-39 years | 3 participants |
| Age, Customized 40-49 years | 16 participants |
| Age, Customized 50-59 years | 10 participants |
| Age, Customized 60-69 years | 6 participants |
| Age, Customized | 49.7 years STANDARD_DEVIATION 9.3 |
| Cell Type Adenocarcinoma, Unspecified | 4 participants |
| Cell Type Adenosquamous | 6 participants |
| Cell Type Mixed Epithelial Carcinoma | 1 participants |
| Cell Type Squamous Cell Carcinoma | 24 participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 35 |
| serious Total, serious adverse events | 15 / 35 |
Outcome results
Primary
Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0): Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response (PR) is 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. Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease.
Time frame: every other cycle for the first 6 months; then every 3 months x 2; then every 6 months
Population: Total number of eligible and evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Cetuximab) | Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Stable disease | 11 participants |
| Treatment (Cetuximab) | Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Disease progression | 23 participants |
| Treatment (Cetuximab) | Objective Tumor Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) | Indeterminate | 1 participants |
Primary
Progression-free Survival Greater Than 6 Months
Time frame: At 6 months
Population: Total number of eligible and evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Cetuximab) | Progression-free Survival Greater Than 6 Months | Yes | 5 participants |
| Treatment (Cetuximab) | Progression-free Survival Greater Than 6 Months | No | 30 participants |
Secondary
Duration of Objective Response Rate
Time frame: Up to 5 years
Secondary
Duration of Overall Survival
Time frame: From study entry to death or the date of last contact, up to 5 years
Secondary
Duration of Progression-free Survival
Time frame: From study entry until disease progression, death or date of last contact, up to 5 years
Secondary
Frequency and Severity of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Time frame: Up to 5 years