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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00653328
• Other study ID #: VICC GYN 0288
• Secondary ID: VU-VICC-GYN-0288
• Status: Terminated
• Phase: Phase 2
• First received: April 3, 2008
• Last updated: May 16, 2012
• Start date: May 2003
• Est. completion date: March 2009

Study information

• Verified date: May 2012
• Source: Vanderbilt-Ingram Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma, Papillary
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Peritoneal Cavity Cancer
• Peritoneal Neoplasms

Intervention

Drug:
• atrasentan hydrochloride
Atrasentan 10 mg orally everyday continuously beginning on Day 1.
• doxil
50 mg/m2 intravenously every 28 days

Locations

Country	Name	City	State
United States	The Jones Clinic	Germantown	Tennessee
United States	Jackson-Madison County Hospital	Jackson	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	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt-Ingram Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Date on study to the date of measured progressive disease, every 2 cycles (2 months)	No
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	At month 2 and monthly thereafter to cessation of treatment	No
Secondary	Overall Survival		Date on study to date of death from any cause	No
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	Weekly for 2 weeks, then monthly for 5 months	Yes