Ph II Atrasentan + DOXIL in Recurrent Ovarian/Fallopian/Peritoneal Serous Papillary Adenocarcinoma

Phase 2

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Therapeutic Intervention	atrasentan hydrochloride	-
Therapeutic Intervention	doxil	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Locations (6): The Jones Clinic
🇺🇸
Germantown, Tennessee, United States
Vanderbilt-Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Kentuckiana Cancer Institute
🇺🇸
Louisville, Kentucky, United States
Central Georgia Hematology Oncology Associates, P.C.
🇺🇸
Macon, Georgia, United States
St. Thomas Health Services
🇺🇸
Nashville, Tennessee, United States
Jackson-Madison County Hospital
🇺🇸
Jackson, Tennessee, United States