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A Phase 2 Study of AZD2171 in Patients With Recurrent Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer

Phase 2
18 Years
Not Enrolling
Fallopian Tube Cancer, Primary Peritoneal Cavity Cancer, Recurrent Ovarian Epithelial Cancer, Stage I Ovarian Epithelial Cancer, Stage II Ovarian Epithelial Cancer

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Trial Information

A Phase 2 Study of AZD2171 in Patients With Recurrent Ovarian, Primary Peritoneal Serous or Fallopian Tube Cancer


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).


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.

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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Time Frame:

Up to 12 months

Safety Issue:


Principal Investigator

Ursula Matulonis

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

October 2005

Completion Date:

January 2011

Related Keywords:

  • Fallopian Tube Cancer
  • Primary Peritoneal Cavity Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Stage I Ovarian Epithelial Cancer
  • Stage II Ovarian Epithelial Cancer
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Ovarian Neoplasms



Dana-Farber Cancer Institute Boston, Massachusetts  02115