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

• Sponsor: Vanderbilt-Ingram Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00653328
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 15
• Locations: 6
• Arm: 1
• Duration (Months): 70
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cavity Cancer	Drug: atrasentan hydrochloride; Drug: doxil	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: May 1, 2003
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Therapeutic Intervention	Drug: atrasentan hydrochloride; Atrasentan 10 mg orally everyday continuously beginning on Day 1.; Other Names: ABT-627 Xinlay ; Drug: doxil; 50 mg/m2 intravenously every 28 days; Other Names: pegylated liposomal doxorubicin hydrochloride (Doxil)

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. Overall Survival [Date on study to date of death from any cause]

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Georgia Hematology Oncology Associates, P.C.	Macon	Georgia	United States	31201
2	Kentuckiana Cancer Institute	Louisville	Kentucky	United States	40202
3	The Jones Clinic	Germantown	Tennessee	United States	38138
4	Jackson-Madison County Hospital	Jackson	Tennessee	United States	383013956
5	St. Thomas Health Services	Nashville	Tennessee	United States	37205
6	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt-Ingram Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marta Crispens, MD, Vanderbilt-Ingram Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marta Crispens, MD, Associate Professor; Gynecological Oncologist, Vanderbilt-Ingram Cancer Center
• ClinicalTrials.gov Identifier: NCT00653328
• Other Study ID Numbers: VICC GYN 0288; VU-VICC-GYN-0288; VU-VICC-020947
• First Posted: Apr 4, 2008
• Last Update Posted: May 23, 2012
• Last Verified: May 1, 2012

• Keywords provided by Marta Crispens, MD, Associate Professor; Gynecological Oncologist, Vanderbilt-Ingram Cancer Center: recurrent ovarian epithelial cancer; fallopian tube cancer; peritoneal cavity cancer
• Additional relevant MeSH terms: Adenocarcinoma; Fallopian Tube Neoplasms; Adenocarcinoma, Papillary; Doxorubicin; Liposomal doxorubicin; Atrasentan

Study Results

Participant Flow

Recruitment Details	Recruitment period = 5/28/2003 through 9/15/2006
Pre-assignment Detail	A total of 16 people signed consent to take part in this study; of those, one withdrew consent before beginning treatment.

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
Period Title: Overall Study
STARTED	15
COMPLETED	0
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 46.7%
>=65 years	8 53.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (1)
Sex: Female, Male (Count of Participants)
Female	15 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Median Time to Tumor Progression
Description	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)

Outcome Measure Data

Analysis Population Description

Patients available for measurement of tumor response. One patient withdrew after beginning treatment.

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
Measure Participants	14
Median (Full Range) [Months]	1 (2.9)

2. Secondary Outcome

Title	Number of Patients With Objective Response
Description	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

Outcome Measure Data

Analysis Population Description

Patients who were available for measurement of tumor response.One patient withdrew after beginning treatment and was not available for measurement.

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
Measure Participants	14
Complete Response	0 0%
Partial Response	0 0%
Stable Disease	3 20%
Progressive Disease	11 73.3%

3. Secondary Outcome

Title	Overall Survival
Time Frame	Date on study to date of death from any cause

Outcome Measure Data

Analysis Population Description

All patients who received treatment. Two patients alive at last follow-up.

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
Measure Participants	13
Median (Full Range) [Months]	10

4. Secondary Outcome

Title	Number of Patients With Worst Grade Toxicities
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
Measure Participants	15
Number of participants with worst grade toxicity 1	5 33.3%
Number of participants with worst grade toxicity 2	3 20%
Number of participants with worst grade toxicity 3	3 20%
Number of participants with worst grade toxicity 4	0 0%
Number of participants with worst grade toxicity 5	0 0%

Adverse Events

Arm/Group Title	Altrasentan + Doxil
Arm/Group Description	Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days
All Cause Mortality
	Altrasentan + Doxil
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Altrasentan + Doxil
	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)
Cardiac disorders
Pericardial effusion	1/15 (6.7%)	1
Gastrointestinal disorders
Nausea	2/15 (13.3%)	2
Vomiting	2/15 (13.3%)	2
abdominal cramping	1/15 (6.7%)	1
General disorders
Fatigue	3/15 (20%)	5
Death	1/15 (6.7%)	1
edema	1/15 (6.7%)	2
fever	2/15 (13.3%)	2
fatigue	2/15 (13.3%)	3
Investigations
hemoglobin	2/15 (13.3%)	2
Metabolism and nutrition disorders
Dehydration	1/15 (6.7%)	1
Hypoalbuminemia	1/15 (6.7%)	1
Hyponatremia	1/15 (6.7%)	2
Renal and urinary disorders
urinary frequency	1/15 (6.7%)	1
Reproductive system and breast disorders
pelvic pain	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/15 (13.3%)	2
Hypoxia	1/15 (6.7%)	2
Pleural effusion	2/15 (13.3%)	2
Vascular disorders
Thromboembolism	1/15 (6.7%)	1
hot flashes	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Altrasentan + Doxil
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Hemoglobin	7/15 (46.7%)	50
Leukocytes	4/15 (26.7%)	29
Cardiac disorders
arrhythmias	1/15 (6.7%)	1
chest pain	1/15 (6.7%)	1
Endocrine disorders
endrocrine	1/15 (6.7%)	1
Eye disorders
dry eye	2/15 (13.3%)	3
tearing	1/15 (6.7%)	2
Gastrointestinal disorders
Nausea	5/15 (33.3%)	8
Vomiting	4/15 (26.7%)	5
Abdominal Pain	4/15 (26.7%)	4
constipation	6/15 (40%)	8
dehydration	1/15 (6.7%)	1
diarrhea	2/15 (13.3%)	2
dysphagia	2/15 (13.3%)	2
GI other	7/15 (46.7%)	12
mouth dryness	1/15 (6.7%)	1
General disorders
fatigue	10/15 (66.7%)	34
edema	8/15 (53.3%)	13
fever	2/15 (13.3%)	2
rigors, chills	1/15 (6.7%)	1
hemorrhage	1/15 (6.7%)	1
constitutional symptoms	1/15 (6.7%)	1
Hepatobiliary disorders
SGOT	2/15 (13.3%)	5
SGPT	2/15 (13.3%)	3
Infections and infestations
infectious wound	1/15 (6.7%)	2
infection without neutropenia	2/15 (13.3%)	2
Injury, poisoning and procedural complications
bruising	1/15 (6.7%)	1
Investigations
neutrophils, granulocytes	2/15 (13.3%)	25
platelets	1/15 (6.7%)	14
weight gain	4/15 (26.7%)	4
alkaline phosphatase	2/15 (13.3%)	2
creatinine	2/15 (13.3%)	2
Metabolism and nutrition disorders
Hyponatremia	1/15 (6.7%)	2
hyperglycemia	5/15 (33.3%)	11
hypocalcemia	1/15 (6.7%)	1
hypokalemia	1/15 (6.7%)	2
metabolic, other	3/15 (20%)	5
Musculoskeletal and connective tissue disorders
arthritis	1/15 (6.7%)	1
arthralgia	1/15 (6.7%)	2
neck pain	1/15 (6.7%)	12
pain	2/15 (13.3%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hypoalbuminemia	1/15 (6.7%)	1
tumor pain	1/15 (6.7%)	1
Nervous system disorders
dizziness	1/15 (6.7%)	1
neuropathy	7/15 (46.7%)	12
headache	4/15 (26.7%)	7
Psychiatric disorders
anorexia	2/15 (13.3%)	3
insomnia	3/15 (20%)	7
mood alteration	4/15 (26.7%)	6
Renal and urinary disorders
Urinary urgency	1/15 (6.7%)	2
dysuria	2/15 (13.3%)	2
Renal, other	2/15 (13.3%)	2
Reproductive system and breast disorders
pelvic pain	2/15 (13.3%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/15 (53.3%)	11
Allergic Rhinitis	3/15 (20%)	5
pleuritic pain	1/15 (6.7%)	1
cough	4/15 (26.7%)	4
hypoxia	1/15 (6.7%)	1
pulmonary, other	2/15 (13.3%)	2
Skin and subcutaneous tissue disorders
alopecia	4/15 (26.7%)	11
rash	3/15 (20%)	8
Vascular disorders
Hot flashes	2/15 (13.3%)	2
hypotension	2/15 (13.3%)	2
sweating	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.