Phase I/II Study of Cediranib and Olaparib in Combination for Treatment of Recurrent Platinum-Sensitive Papillary-Serous Ovarian, Fallopian Tube, or Peritoneal Cancer or for Treatment of Recurrent Triple-Negative Breast Cancer
| City: |
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Boston |
| State: |
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Massachusetts |
| Zip Code: |
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02115 |
| Conditions: |
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Breast Cancer - Fallopian Tube Cancer - Ovarian Cancer - Malignant Tumor of Peritoneum |
| Purpose: |
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RATIONALE: Cediranib maleate and olaparib may stop the growth of tumor cells by blocking
some of the enzymes needed for cell growth. Cediranib maleate may also stop the growth of
tumor cells by blocking blood flow to the tumor. Giving cediranib maleate together with
olaparib may kill more tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects and the best dose of
cediranib maleate when given together with olaparib and to see how well they work compared
to cediranib maleate alone in treating patients with recurrent ovarian epithelial cancer,
fallopian tube cancer, peritoneal cancer, or recurrent triple-negative breast cancer.
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| Study Summary: |
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OBJECTIVES:
Primary
- Assess the maximum-tolerated dose of cediranib maleate in combination with olaparib in
patients with recurrent platinum-sensitive papillary-serous ovarian, fallopian tube, or
peritoneal cancer or metastatic triple-negative breast cancer. (Phase I)
- Assess the efficacy, in terms of progression-free survival (PFS), of cediranib maleate
with versus without olaparib in patients with recurrent grade 2 or 3 platinum-sensitive
papillary-serous ovarian, fallopian tube, or peritoneal cancer. (Phase II)
Secondary
- Assess the toxicity of this regimen in these patients. (Phase I)
- Assess the clinical benefit, PFS, and overall survival of patients treated with this
regimen. (Phase I)
- Assess tumor response, clinical response benefit, and overall survival of patients
treated with these regimens. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a randomized
phase II study.
- Phase I: Patients receive oral cediranib maleate once daily and oral olaparib twice
daily on days 1-28. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.
- Phase II: Patients are stratified according to prior antiangiogenic therapy (yes vs no)
and BRCA mutation status (carrier vs non-carrier vs unknown). Patients are randomized
to 1 of 2 treatment arms.
- Arm I: Patients receive oral cediranib maleate once daily on days 1-28.
- Arm II: Patients receive oral cediranib maleate once daily and oral olaparib twice
daily on days 1-28.
In both arms, treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 3 years.
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| Criteria: |
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DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed diagnosis of 1 of the following:
- Epithelial ovarian cancer
- Primary peritoneal serous cancer
- Fallopian tube cancer
- Triple-negative metastatic breast cancer (phase I only) (male patients allowed)
- Estrogen receptor-negative disease
- Progesterone receptor-negative disease
- HER2/neu-negative disease
- Measurable disease
- Patients with ovarian cancer, primary peritoneal, and fallopian tube cancer may
either have measurable disease OR elevated CA-125 level ≥ twice upper limit of
normal on 2 separate occasions ≥ 1 day and ≤ 3 months apart
- Platinum-sensitive disease
- Ovarian cancer patients must have had prior chemotherapy that included a
first-line platinum-based regimen with or without IV consolidation chemotherapy
(phase I/II)
- Unlimited number of prior platinum-based therapies for recurrent disease allowed
(phase II)
- Platinum-sensitive disease defined as > 6 months since platinum therapy before
recurrence (phase II)
- Must have had response (and no disease progression) while on the
platinum-containing regimen
- Recurrent breast cancer after prior doxorubicin- and taxane-containing regimen AND ≥
1 prior chemotherapy for metastatic breast cancer (phase I)
- No untreated brain metastases, spinal cord compression, symptomatic brain metastases,
or leptomeningeal disease by CT or MRI scans
PATIENT CHARACTERISTICS:
- Menopausal status not specified
- ECOG performance status 0-1 (Karnofsky 60-100%)
- Life expectancy > 6 months
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and/or ALT ≤ 2.5 times ULN
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Proteinuria ≤ 1+ on 2 consecutive dipsticks taken < 1 week apart OR < 1 g of protein
by 24-hour urine collection
- Troponin T or I normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception before, during, and for 3 months
after treatment discontinuation
- No other malignancy within the past 5 years except adequately treated limited-stage
basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast or
cervix, or curatively treated early-stage cancer with no evidence of recurrent
disease and judged by the investigator to be at low risk of recurrence
- Must be able to tolerate oral medication
- No gastrointestinal illness that would preclude absorption of cediranib maleate or
olaparib
- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to cediranib maleate or olaparib
- None of the following:
- Myocardial infarction within the past 6 months
- QTc prolongation > 500 msec or other significant ECG abnormality within the past
14 days
- NYHA classification of grade III-IV cardiac disease
- Condition requiring concurrent use of drugs or biologics with pro-arrhythmic
potential
- No stroke or transient ischemic attack within the past 6 months
- No evidence of pre-existing inadequately controlled hypertension (defined as a
systolic BP of > 140 mmHg or a diastolic BP of > 90 mmHg), and must have a normal
blood pressure (≤ 140/90 mmHg) taken in the clinic setting by a medical professional
within 2 weeks prior to starting study
- Patients with hypertension may be managed with up to a maximum of three
antihypertensive medications
- Patients who are on three antihypertensive medications must be actively followed
by a cardiologist or blood pressure specialist for management of blood pressure
while on protocol
- No prior hypertensive crisis or hypertensive encephalopathy
- No clinically significant peripheral vascular disease or vascular disease (aortic
aneurysm or aortic dissection)
- No unstable angina
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
- No signs and/or symptoms of bowel obstruction
- No dependency on IV hydration or total parenteral nutrition
- No evidence of coagulopathy or bleeding diathesis
- No uncontrolled intercurrent illness including, but not limited to, any of the
following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness and/or social situations that would limit compliance with
study requirements
- No known HIV positivity
- No peripheral neuropathy ≥ grade 2
- No significant traumatic injury in the past 28 days
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Prior hormonal-based therapy for ovarian, primary peritoneal serous, fallopian tube
cancer, or breast cancer allowed
- No prior PARP-inhibitor in recurrent or metastatic setting
- No prior antiangiogenic agent in recurrent or metastatic setting
- One prior non-platinum-based line of therapy for recurrent disease allowed (phase II)
- At least 3 weeks since prior chemotherapy, radiotherapy, or hormonal therapy and
recovered
- At least 6 weeks since prior nitrosoureas or mitomycin C
- At least 4 weeks since prior and no concurrent investigational agents or trials
- No prior treatment affecting the VEGF pathway in the recurrent setting, including any
of the following:
- Thalidomide
- Bevacizumab
- Sunitinib
- Sorafenib
- No prior oregovomab (OvaRex) or any other antibodies that may interfere with CA-125
measurements
- No major surgical procedure or open biopsy within the past 28 days
- No concurrent medications or substances that are inhibitors or inducers of CYP3A4 or
CYP1A2
- No concurrent natural herbal products or other folk remedies
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| NCT ID: |
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NCT01115829 |
| Primary Contact: |
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Principal Investigator
Joyce F. Liu, MD
Dana-Farber Cancer Institute
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| Backup Contact: |
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N/A |
| Location Contact: |
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Boston, Massachusetts 02115
United States
Joyce F. Liu, MD
Phone: 617-632-5269
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 18, 2013 |
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