Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer
Conditions
Keywords
recurrent ovarian epithelial cancer, fallopian tube cancer, peritoneal cavity cancer
Brief summary
RATIONALE: There is emerging data to suggest that the optimal use of angiogenesis inhibitors may be in combination with chemotherapy. The optimal use of atrasentan may be in combination with chemotherapy in women with relapsed and refractory ovarian cancer,fallopian tube cancer, and peritoneal serous papillary adenocarcinoma. Due to its manageable toxicity profile, ease of administration, and activity in both platinum sensitive as well as platinum-resistant patients, Doxil has become the 2nd-line treatment of choice for women with advanced stage ovarian cancer that has progressed following 1st-line platinum/taxane therapy. PURPOSE: To determine if a treatment combination of atrasentan + Doxil is an effective 2nd line treatment in patients with recurrent ovarian cancer, fallopian tube cancer, or peritoneal cancer.
Detailed description
OBJECTIVES: Primary * To determine the median time to tumor progression in patients with recurrent ovarian epithelial cancer, fallopian tube adenocarcinoma, or peritoneal serous papillary adenocarcinoma treated with Doxil and atrasentan hydrochloride. Secondary * To determine the objective response rate and survival of patients treated with this regimen. * To determine the toxicity of this regimen in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to response to prior treatment with platinum-taxane (sensitive vs resistant). Patients will be administered Doxil 50 mg/m2 intravenous every 28 days and take atrasentan 10 mg orally everyday continuously beginning on Day 1. Patients will continue Doxil + atrasentan in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days and every 2 months thereafter.
Interventions
Atrasentan 10 mg orally everyday continuously beginning on Day 1.
DRUGdoxil
50 mg/m2 intravenously every 28 days
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma arising from the ovary, fallopian tubes, or peritoneum (i.e., peritoneal serous papillary adenocarcinoma) * Received prior treatment with either cisplatin or carboplatin in combination with paclitaxel or docetaxel as first-line chemotherapy * Radiographic evidence of progressive disease and/or a doubling of CA-125 levels ≥ 70 IU/mL following first-line chemotherapy * Measurable disease as defined by RECIST criteria * No CNS metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Absolute neutrophil count ≥ 1,500/μL * Hemoglobin ≥ 9.5 g/dL * Platelets \> 100,000/μL * Serum creatinine ≤ 1.5 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN * AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if liver metastases are present) * LVEF ≥ 50% by MUGA * Not pregnant or nursing * Negative pregnancy test * Surgically sterile or must use effective contraception * No known HIV positivity or AIDS * No uncontrolled heart disease, diabetes, or other medical condition that would place the patient at unacceptably high risk for toxicity * No New York Heart Association class I-IV heart failure
Exclusion criteria
Not specified PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from all prior toxicities to ≤ grade 1 by NCI-CTC Version 2 criteria * No other prior systemic therapies for this cancer except cisplatin or carboplatin in combination with paclitaxel or docetaxel as first-line chemotherapy * More than 4 weeks since prior chemotherapy * No concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Tumor Progression | Date on study to the date of measured progressive disease, every 2 cycles (2 months) | Tumor progression is determined by appropriate imaging techniques according to RECIST criteria or by CA-125 serum level \>=2x baseline and \>=70 IU/ml, confirmed by a second determination at least 28 days after the first determination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Objective Response | At month 2 and monthly thereafter to cessation of treatment | Patient response to treatment: Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started, or appearance of \>= 1 new lesions, and/or 2x CA-125 levels to \>=70 IU/ml, confirmed by second measurement after 28 days Complete response (CR): disappearance of all target lesions Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD |
| Overall Survival | Date on study to date of death from any cause | — |
| Number of Patients With Worst Grade Toxicities | Weekly for 2 weeks, then monthly for 5 months | Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria |
Countries
United States
Participant flow
Recruitment details
Recruitment period = 5/28/2003 through 9/15/2006
Pre-assignment details
A total of 16 people signed consent to take part in this study; of those, one withdrew consent before beginning treatment.
Participants by arm
| Arm | Count |
|---|---|
| Altrasentan + Doxil Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Disease progression | 10 |
| Overall Study | Drug manufacturer no longing making drug | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Altrasentan + Doxil |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age Continuous | 66 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 15 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 | 15 / 15 |
| serious Total, serious adverse events | 5 / 15 |
Outcome results
Primary
Median Time to Tumor Progression
Tumor progression is determined by appropriate imaging techniques according to RECIST criteria or by CA-125 serum level \>=2x baseline and \>=70 IU/ml, confirmed by a second determination at least 28 days after the first determination
Time frame: Date on study to the date of measured progressive disease, every 2 cycles (2 months)
Population: Patients available for measurement of tumor response. One patient withdrew after beginning treatment.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Altrasentan + Doxil | Median Time to Tumor Progression | 1 Months | Full Range 2.9 |
Secondary
Number of Patients With Objective Response
Patient response to treatment: Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started, or appearance of \>= 1 new lesions, and/or 2x CA-125 levels to \>=70 IU/ml, confirmed by second measurement after 28 days Complete response (CR): disappearance of all target lesions Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD
Time frame: At month 2 and monthly thereafter to cessation of treatment
Population: Patients who were available for measurement of tumor response.One patient withdrew after beginning treatment and was not available for measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Altrasentan + Doxil | Number of Patients With Objective Response | Complete Response | 0 participants |
| Altrasentan + Doxil | Number of Patients With Objective Response | Progressive Disease | 11 participants |
| Altrasentan + Doxil | Number of Patients With Objective Response | Partial Response | 0 participants |
| Altrasentan + Doxil | Number of Patients With Objective Response | Stable Disease | 3 participants |
Secondary
Number of Patients With Worst Grade Toxicities
Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria
Time frame: Weekly for 2 weeks, then monthly for 5 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Altrasentan + Doxil | Number of Patients With Worst Grade Toxicities | Number of participants with worst grade toxicity 1 | 5 participants |
| Altrasentan + Doxil | Number of Patients With Worst Grade Toxicities | Number of participants with worst grade toxicity 2 | 3 participants |
| Altrasentan + Doxil | Number of Patients With Worst Grade Toxicities | Number of participants with worst grade toxicity 3 | 3 participants |
| Altrasentan + Doxil | Number of Patients With Worst Grade Toxicities | Number of participants with worst grade toxicity 4 | 0 participants |
| Altrasentan + Doxil | Number of Patients With Worst Grade Toxicities | Number of participants with worst grade toxicity 5 | 0 participants |
Secondary
Overall Survival
Time frame: Date on study to date of death from any cause
Population: All patients who received treatment. Two patients alive at last follow-up.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Altrasentan + Doxil | Overall Survival | 10 Months |