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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study of Atrasentan (ABT-627) Plus DOXIL in Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Serous Papillary Adenocarcinoma Following Platinum + Taxane Therapy

Conditions
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Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer

Intervention / Treatment
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* Drug: atrasentan hydrochloride
* Drug: doxil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Intervention<br> | Drug: atrasentan hydrochloride<br>* Atrasentan 10 mg orally everyday continuously beginning on Day 1.<br>* Other names: Xinlay;Drug: doxil<br>* 50 mg/m2 intravenously every 28 days<br>* Other names: pegylated liposomal doxorubicin hydrochloride (Doxil);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Date on study to the date of measured progressive disease, every 2 cycles (2 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At month 2 and monthly thereafter to cessation of treatment | 
| Overall Survival |  | Date on study to date of death from any cause | 
| 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 | Weekly for 2 weeks, then monthly for 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian epithelial cancer, fallopian tube cancer, peritoneal cavity cancer