Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Adenocarcinoma

Recurrence

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Atrasentan

Endothelin A Receptor Antagonists

Endothelin Receptor Antagonists

atrasentan hydrochloride

Gary Gordon, MD, PhD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase III trial to determine the effectiveness of atrasentan in treating patients who have prostate cancer that has not responded to hormone therapy.

OBJECTIVES:

* Determine the safety of atrasentan in patients with hormone-refractory prostate cancer.
* Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral atrasentan once daily for 3 years in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month and then every 3 months for 2 years.

PROJECTED ACCRUAL: Approximately 1,400 patients will be accrued for this study.

Atrasentan in Treating Patients With Prostate Cancer

A Phase III Extension Study to Evaluate the Safety of 10 mg Atrasentan in Men With Hormone-Refractory Prostate Cancer

Abbott

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Michael A. Carducci, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well atrasentan works in treating patients with locally recurrent or metastatic kidney cancer.

OBJECTIVES:

* Determine the 6-month progression-free survival rate, in terms of proportion of those with measurable disease or bone metastases only, of patients with locally recurrent or metastatic renal cell carcinoma treated with atrasentan (measurable disease stratum closed to accrual as of 7/16/04).
* Determine the toxicity of this drug in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prior immunotherapy/biologic therapy (yes vs no) and characteristic of disease (measurable vs bone metastases only) (measurable disease stratum closed to accrual as of 7/16/04).

Patients receive oral atrasentan once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 180 patients (90 per stratum \[with or without prior therapy\]) will be accrued for this study within 6 months (based on prior accrual, the bone metastases only group \[specifically patients who have received 1 prior therapy\] is the only stratum open for accrual).

Atrasentan in Treating Patients With Locally Recurrent or Metastatic Kidney Cancer

A Phase II Trial Evaluating Atrasentan In Patients With Advanced Renal Cell Carcinoma

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Group Chair

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Adenocarcinoma, Papillary

Fallopian Tube Neoplasms

Adnexal Diseases

Genital Diseases, Female

Genital Neoplasms, Female

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Taxane

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Atrasentan 10 mg orally everyday continuously beginning on Day 1.

doxil

Marta Crispens, MD

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.

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.

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

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

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

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

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

Vanderbilt-Ingram Cancer Center

Associate Professor; Gynecological Oncologist

Atrasentan, 10 mg orally everyday continuously beginning on Day 1. Doxil. 50 mg/m2 intravenously every 28 days

Altrasentan + Doxil

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Marta Crispens, M.D.

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

Median Time to Tumor Progression

Complete Response

Partial Response

Stable Disease

Progressive Disease

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

Number of Patients With Objective Response

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

Overall Survival

Number of participants with worst grade toxicity 1

Number of participants with worst grade toxicity 2

Number of participants with worst grade toxicity 3

Number of participants with worst grade toxicity 4

Number of participants with worst grade toxicity 5

Number of Patients With Worst Grade Toxicities

Overall Study

Neoplasm Metastasis

Anti-Inflammatory Agents

Docetaxel

Prednisone

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

Docetaxel given IV and prednisone given orally

docetaxel

prednisone

placebo

David I. Quinn, MD

Maha Hadi A. Hussain, MD

Primo N. Lara, MD

Mark Garzotto, MD

RATIONALE: Drugs used in chemotherapy, such as docetaxel, prednisone, and atrasentan work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether docetaxel, prednisone, and atrasentan are more effective than docetaxel and prednisone in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying docetaxel, prednisone, and atrasentan to see how well they work compared to docetaxel and prednisone in treating patients with stage IV prostate cancer and bone metastases that did not respond to previous hormone therapy.

OBJECTIVES:

Primary

* Compare the survival and progression-free survival of patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo.

Secondary

* Compare pain progression of patients treated with these regimens.
* Compare the qualitative and quantitative toxicity of these regimens in these patients.
* Compare the quality of life, in terms of palliation of metastatic bone pain and improvement in functional status, of patients treated with these regimens.
* Compare prostate-specific antigen (PSA) response rates in patients treated with these regimens.
* Compare objective response in patients with measurable disease treated with these regimens.
* Determine whether a 30% reduction in PSA and the slope of PSA from baseline to 3 months is a surrogate marker for survival in patients treated with these regimens.
* Correlate PSA progression with clinical progression and death in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease progression (measurable or non-measurable disease progression vs prostate-specific antigen progression only), use of bisphosphonates at study entry (yes vs no), worst pain, measured by the Brief Pain Inventory "pain" scale (\< grade 4 vs ≥ grade 4), and extraskeletal metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks in the absence of disease progression\* or unacceptable toxicity.
* Arm II: Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks in the absence of disease progression\* or unacceptable toxicity.

NOTE: \*Patients with PSA progression alone will be allowed to continue treatment

Quality of life is assessed at baseline, before courses 4, 7, and 10, and then after completion of study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 3 years from study entry.

PROJECTED ACCRUAL: A total of 930 patients will be accrued for this study within 4 years.

S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy

Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer

http://swog.org/Visitors/Download/Policies/Policy43.pdf

Pain palliation is the proportion of patients showing a two-point reduction in the Worst Pain score (WPS) maintained for two consecutive assessments with no increase in analgesic use. Increase in analgesic use is defined as an increase in Analgesic code Level to 2 (weak opioid) or 3 (strong opioid). Patients will be classified as pain palliated or not palliated. Patients with a WPS of "0" will be defined as "stable" if their WPS remains "0" for Weeks 7 and 10 with no increase in analgesic use, but they will not be categorized as responders. Pain palliation response is measured by BPI short form that has the following: yes/no question about pain today; 4 pain rating questions (worst pain, least pain, average pain, and current pain); pain medications and pain relief; 7 items addressing effect of pain on functioning. For patients who continue to receive treatment beyond 12 treatment cycles, the Worst Pain item is measured by Pain Medication Log and Pain Assessment

Functional status will be measured with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index. The FACT-P also addresses four general domains of QOL (physical, functional, emotional, and social well-being subscales) as well as symptom concerns associated with prostate cancer and its treatment.

Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact.

Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients without progression are censored at date of last contact. Disease progression is defined by confirmed bone disease progression, soft tissue or pain progression.

Pain progression is defined as patients reporting an increase of at least two Worst Pain points, maintained for at least two consecutive assessments, increase to Level 3 (strong opioid) on the Pain Medication Log Analgesic Code for patients receiving Level 2 (weak opioid) analgesics at randomization, or an increase to Level 2 or 3 analgesics for patients receiving Level 0 or 1 analgesics at randomization.

Only adverse events that are possibly, probably or definitely related to study drug are reported.

PSA Partial Response: Greater than or equal to 50% reduction in baseline PSA. There must be no evidence of soft tissue progression, or confirmed none disease progression, or pain progression.

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. PSA ≤ .2 ng/ml. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.

SWOG Cancer Research Network

Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.

Arm I: Placebo

Arm II: Atrasentan

Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

placebo: Given orally

Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.

atrasentan hydrochloride: Given orally

docetaxel: Docetaxel given IV and prednisone given orally

prednisone: Docetaxel given IV and prednisone given orally

Total

Age, Continuous

Ethnicity (NIH/OMB)

White

Black

Asian

Unknown

Race/Ethnicity, Customized

Serum PSA

Type of Progression at study entry

Bisphosphonate use at study entry

score \>=4 vs \<4 in the Brief Pain Inventory scale for worst pain

Brief Pain Inventory, worst pain

Metastases

Previous prostatectomy

SWOG Performance status:

0 = Fully active, able to carry on all pre-disease performance without restriction.

1. = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
2. = Ambulatory and capable of self-care but unable to carry out any work activities; up and about more than 50% of waking hours.
3. = Capable of limited self-care, confined to bed or chair more than 50% of waking hours.

Performance status

Pathologists grade prostate cancers using numbers from 1 to 5 based on how much the cells in the cancerous tissue look like normal tissue. This is called the Gleason system.

If the cancerous tissue looks like normal tissue, a grade of 1 is assigned. If the cancer cells look very abnormal, a grade of 5 is assigned. Grades 2-4 have features in between these extremes.

Since prostate cancers often have areas with different grades, a grade is assigned to the 2 areas that make up most of the cancer. These 2 grades are added to yield the Gleason score. The highest a Gleason score can be is 10.

Gleason score

A total of 1038 patients were randomized to this study, 42 of which were ineligible. Baseline analysis population includes 994 patients (excluding the 42 ineligible patients and 2 additional patients who withdrew all consent prior to receiving protocol treatment).

Dr. David I Quinn

The primary analysis was by intention to treat and the Hochberg procedure was used for multiple testing of co-primary endpoints. Assuming a 4 year accrual, 2.5 years of follow-up, and 930 eligible patients, the study was designed to have 87% power to detect a 25% increase from 18.0 months to 22.5 months in median overall survival with a one-sided log rank with alpha of 0.0125.

Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.

The primary analysis was by intention to treat and the Hochberg procedure was used for multiple testing of co-primary endpoints. Assuming a 4 year accrual, 2.5 years of follow-up, and 930 eligible patients, the study was designed to have 87% power to detect a 25% increase from 6.0 months to 7.5 months in median overall survival with a one-sided log rank with alpha of 0.0125.

Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.

Only those patients who progressed on study were included in this analysis. The proportion of patients with pain progression is calculated using number of patients with pain progression as the numerator and the total number of patients who progressed on study as the denominator.

Compare Pain Progression Between the Two Study Arms.

ALT, SGPT (serum glutamic pyruvic transaminase)

AST, SGOT

Adult respiratory distress syndrome (ARDS)

Albumin, serum-low (hypoalbuminemia)

Alkaline phosphatase

Allergic reaction/hypersensitivity

Allergy/Immunology-Other (Specify)

Amylase

Anorexia

Arthritis (non-septic)

Aspiration

Auditory/Ear-Other (Specify)

Bilirubin (hyperbilirubinemia)

Blood/Bone Marrow-Other (Specify)

CNS cerebrovascular ischemia

CPK (creatine phosphokinase)

Calcium, serum-low (hypocalcemia)

Cardiac Arrhythmia-Other (Specify)

Cardiac General-Other (Specify)

Cardiac troponin I (cTnI)

Cardiac troponin T (cTnT)

Cardiac-ischemia/infarction

Conduction abnormality NOS

Confusion

Constipation

Cough

Creatinine

Dehydration

Diarrhea

Dizziness

Dry mouth/salivary gland (xerostomia)

patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo

Compare Qualitative and Quantitative Toxicity Between the Two Study Arms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Atrasentan in Treating Patients With Prostate Cancer	NCT00046943	Prostate Cancer	atrasentan hydr...	19 Years -	National Cancer Institute (NCI)
Atrasentan in Treating Patients With Locally Recurrent or Metastatic Kidney Cancer	NCT00039429	Kidney Cancer	atrasentan hydr...	18 Years - 120 Years	Eastern Cooperative Oncology Group
Ph II Atrasentan + DOXIL in Recurrent Ovarian/Fallopian/Peritoneal Serous Papillary Adenocarcinoma	NCT00653328	Fallopian Tube ... Ovarian Cancer Peritoneal Cavi...	atrasentan hydr... doxil	18 Years -	Vanderbilt-Ingram Cancer Center
Atrasentan in Treating Patients With Locally Recurrent or Metastatic Kidney Cancer	NCT00039429	Kidney Cancer	atrasentan hydr...	18 Years - 120 Years	Eastern Cooperative Oncology Group
S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy	NCT00134056	Metastatic Canc... Prostate Cancer	atrasentan hydr... docetaxel prednisone placebo	18 Years -	SWOG Cancer Research Network
Atrasentan in Treating Patients With Locally Recurrent or Metastatic Kidney Cancer	NCT00039429	Kidney Cancer	atrasentan hydr...	18 Years - 120 Years	Eastern Cooperative Oncology Group
Atrasentan in Treating Patients With Prostate Cancer	NCT00046943	Prostate Cancer	atrasentan hydr...	19 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for atrasentan hydrochloride