AZD2171 in Treating Patients With Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00275028
First received: January 10, 2006
Last updated: February 1, 2013
Last verified: January 2013
  Purpose

This phase II trial is studying how well AZD2171 works in treating patients with recurrent ovarian, peritoneal, or fallopian tube cancer. AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor


Condition Intervention Phase
Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Recurrent Ovarian Epithelial Cancer
Stage I Ovarian Epithelial Cancer
Stage II Ovarian Epithelial Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD2171 in Patients With Recurrent Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Clinical response benefit (modified Gynecologic Cancer InterGroup [GCIG] cancer antigen [CA]-125 response or stable disease) based on the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Modified GCIG CA-125 response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Duration of modified GCIG CA-125 response [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Correlation of clinical outcomes with an angiogenic profile derived from serial assessments of soluble VEGFR2, circulating endothelial cell levels, and VEGFR phosphorylation in circulating endothelial cells [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Pharmacogenetic differences in kdr/flk-1, HIF1alpha, p53, and eNOS in PBMCs [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Determine whether oncogenic mutations predict response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: October 2005
Study Completion Date: January 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate)
Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy of AZD2171 in platinum sensitive and platinum insensitive disease, based on either RECIST criteria (for patients with measurable cancer radiographically) or clinical response benefit (modified Gynecologic Cancer Intergroup [GCIG] CA-125 response or stable disease for at least 16 weeks).

SECONDARY OBJECTIVES:

I. To assess progression-free survival. II. To assess modified GCIG CA-125 response rate. III. To assess duration of modified GCIG CA-125 response. IV. To assess the safety of the recommended phase 2 dose of AZD2171 in this asymptomatic patient population.

V. To explore the pharmacodynamic effects of AZD2171 by correlating clinical outcomes with an angiogenic profile derived from serial assessments of soluble VEGFR2, circulating endothelial cell levels, and VEGFR phosphorylation in circulating endothelial cells.

VI. To explore pharmacogenetic differences in kdr/flk-1, HIF1alpha, p53, and endothelial nitric oxide synthase (eNOS) in PBMCs from subjects who consent separately for pharmacogenetic studies.

VII. To determine whether oncogenic mutations predict response to AZD2171.

OUTLINE: This is a multicenter study. Patients are stratified according to disease sensitivity (platinum-sensitive disease vs platinum-insensitive disease).

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have histologically or cytologically confirmed epithelial ovarian cancer, primary peritoneal serous cancer, or fallopian tube cancer
  • Patients must have either measurable cancer by RECIST criteria or an elevated CA125 level at least twice the upper limit of normal on two separate occasions at least 1 day but not more than 3 months apart; at least one of the samples should be within 1 week of starting treatment); patients with both an elevated CA125 and measurable cancer will be followed by RECIST criteria
  • Subjects must be asymptomatic or minimally symptomatic
  • Prior therapy:

    • Prior chemotherapy must have included a first-line platinum-based regimen only with or without intravenous consolidation chemotherapy
    • Prior hormonal-based therapy for ovarian, primary peritoneal serous or fallopian tube cancer is acceptable
    • Up to two prior lines of chemotherapy in the recurrent setting are allowed
    • Patients with an initial treatment-free interval of greater than 12 months who have measurable disease are only eligible if they have progressed following re-treatment with a platinum-based regimen as second-line therapy
    • Toxic side effects related to prior chemotherapy or hormonal therapy must have resolved to less than or equal to grade 1 or to baseline (excluding alopecia), or for peripheral neuropathy to less than or equal to grade 2 (Common Toxicity Criteria version 3.0)
    • Subjects may begin AZD2171 at least 3 weeks after their last dose of chemotherapy or hormonal therapy, assuming they are otherwise eligible
  • Life expectancy of greater than 6 months
  • ECOG performance status 0-1 (Karnofsky >= 70%)
  • Absolute neutrophil count at least 1,500/mcL
  • Platelets at least 100,000/mcL
  • Hemoglobin at least 8 g/dL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 × institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional limit of normal
  • Less than or equal to 1+ proteinuria on two consecutive dipsticks taken no less than 1 week apart
  • Troponin T or I within normal institutional limits
  • At present, the potential of AZD2171 for clinically significant drug interactions involving the CYP isozymes is unknown; however, studies of the agent in rats indicated possible suppression of CYP1A that may be of biological significance; eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of AZD2171 will be determined following review of their case by the Principal Investigator
  • Subjects with treated limited stage basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the breast or cervix are eligible; subjects with stage I or II cancer treated with a curative intent are also eligible with no evidence of recurrent disease
  • No evidence of preexisting uncontrolled hypertension; if patient has hypertension, it must be medically controlled (less than 150/90) prior to starting AZD2171
  • AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; it is anticipated that all subjects enrolled in this trial will have undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy as part of their initial cancer treatment, so the likelihood of enrolling a woman of child-bearing potential is low
  • Ability to understand and the willingness to sign a written informed consent document
  • No therapeutic anticoagulation; the use of low dose warfarin (1 mg/day), intermittent doses of tPA (2 mg x 1), or heparin flushes to prophylax against central venous catheter-associated clots is permitted
  • Measurable or non-measurable disease on CT scan or MRI
  • Consider patients who have the following risk factors to be at increased risk; these patients should have increased monitoring:

    • Prior treatment with anthracyclines
    • Prior treatment with trastuzumab
    • A New York Heart Association classification of II controlled with treatment
    • Prior central thoracic radiation therapy (RT), including RT to the heart
    • History of myocardial infarction within 12 months

Exclusion Criteria:

  • Patients who have had chemotherapy, radiotherapy, or major surgery within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier
  • Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 3 weeks; subjects may not have received prior treatment affecting the VEGF pathway, including thalidomide; subjects may not have received prior treatment with oregovomab (OvaRex) or any other antibodies that may interfere with CA-125 measurements; subjects may not have received intraperitoneal therapy within the 4 weeks prior to starting AZD2171 and/or the treating physician must confirm the patient has recurrent disease as opposed to a non-malignant, artificially elevated CA-125 secondary to intraperitoneal administered chemotherapy; confirmation of recurrence may be done by CT scan, magnetic resonance imaging or surgery
  • Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine)
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
  • Mean QTc > 500 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome
  • Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
  • Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; inability to take and absorb orally administered medication
  • Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171
  • Major surgical procedure or medical interference with the peritoneum or pleura within 4 weeks of baseline CA-125 assessments
  • Subjects with a history of an active malignancy during the last 3 years except non-melanomatous skin cancer , in situ breast or cervical cancer or stage I or II cancer treated with a curative intent and no active cancer recurrence
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171
  • No therapeutic anti-coagulation; the use of low dose warfarin (1 mg/day), intermittent doses of tPA (2 mg x 1), or heparin flushes to prophylax against central venous catheter-associated clots is permitted
  • A New York Heart Association classification of III or IV
  • Conditions requiring concurrent use of drugs or biologics with proarrhythmic potentiate; these drugs are prohibited during studies with AZD2171
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275028

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Investigators
Principal Investigator: Ursula Matulonis Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00275028     History of Changes
Other Study ID Numbers: NCI-2013-00036, 05-170, U01CA062490
Study First Received: January 10, 2006
Last Updated: February 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Cediranib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014