Clinical trial NCT00058552: A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer
Official title: A Phase II, Open-label, Multicenter Study to Evaluate the Effect of Tumor-based HER2 Activation on the Efficacy of rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced, Refractory or Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Advanced, refractory, or recurrent ovarian cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2003-04-09
Enrollment: 129
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if the study drug pertuzumab is effective in treating patients with advanced ovarian cancer that is refractory to, or has recurred following, prior chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Willingness to undergo tumor biopsy and disease that is amenable to biopsy (Cohort 1 only)
* Age \>=18 years old
* Advanced, histologically documented carcinoma of the ovary
* Measurable disease with at least one lesion that can be accurately measured per RECIST in at least one dimension (longest dimension recorded). Each lesion must be \>=20 mm when measured by conventional techniques, including palpation, plain X-ray, CT, and MRI, or \>=10 mm when measured by spiral CT.
* Or, clinically or radiologically detectable disease (e.g., ascites, peritoneal deposits, mesenteric thickening or lesions that do not fulfill RECIST for measurable disease). In addition, the subject must have two consecutive pre-treatment CA 125 levels that are both greater than 2× the institutional upper limit of normal (ULN) and \>=40 IU/mL, taken at least 1 week and not more than 3 months apart. The second of the two measurements of CA 125 level should not be drawn within 28 days following the screening biopsy. The later value must be within 2 weeks of starting rhuMAb 2C4 treatment.
* One or more prior platinum-based chemotherapeutic regimens for the management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound
* Life expectancy \>=12 weeks
* ECOG performance status 0 or 1
* Use of an effective means of contraception (for women of childbearing potential)
* Granulocyte count \>=1500/uL, platelet count of \>=75,000/uL, and hemoglobin \>=9 g/dL (hemoglobin may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors; darbopoeitin \[Aranesp\] is permitted)
* Serum bilirubin \<=1.5× the ULN and alkaline phosphatase, AST, and ALT \<=2.5× ULN (ALT, AST, and alkaline phosphatase \<=5× ULN for subjects with liver metastases)
* Serum creatinine \<=1.5× ULN
* International normalized ratio (INR) \<1.5 and activated partial thromboplastin time (aPTT) \<1.5 ULN (except for subjects receiving warfarin)

Exclusion Criteria:

* Prior treatment with experimental anti-cancer agents within 4 weeks prior to Day 1 (the day on which the first rhuMAb 2C4 infusion is administered)
* Prior treatment with HER pathway inhibitors (e.g., Herceptin \[Trastuzumab\], Iressa \[gefitinib\], Tarceva \[erlotinib hydrochloride\], C225, CI1033, and TAK165)
* History or clinical evidence of central nervous system or brain metastases
* Ejection fraction, determined by ECHO, \<50%
* Uncontrolled hypercalcemia (\>11.5 mg/dL)
* Prior exposure to doxorubicin or liposomal doxorubicin \>360 mg/m2 , mitoxantrone \>120 mg/m2 , or idarubicin \>90 mg/m2
* History of other malignancies within 5 years of Day 1 except for adequately treated carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, or basal or squamous cell skin cancer
* History of serious systemic disease, including active infection, uncontrolled hypertension (diastolic blood pressure \>100 mmHg on two consecutive occasions), unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to Day 1, or unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation, paroxysmal supraventricular tachycardia, or controlled hypertension are eligible)
* Ongoing liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* Known human immunodeficiency virus infection
* Pregnancy or lactation
* Major surgery or significant traumatic injury within 3 weeks prior to Day 1 with the exception of tumor biopsy for the purposes of the study
* Inability to comply with study and follow-up procedures
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications

Primary outcomes:
measure: Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes
timeFrame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
Secondary outcomes:
measure: Percentage of Participants With Disease Progression or Death (Progression Free Survival [PFS])
timeFrame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
measure: Median Time of PFS
timeFrame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
measure: Duration of Response
timeFrame: Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab)
measure: Percentage of Participants Who Died
timeFrame: Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years)
measure: Overall Survival
timeFrame: Days 1, 8, and 15 of Cycles 1 and 2, Day 1 of Cycles 3-17, follow-up (30 days after the last dose of pertuzumab) and then every 3 months until death or loss to follow-up (up to 5 years)
measure: Kaplan Meier Estimate of Percentage of Participants Who Were Free of Disease Progression at 3, 6, and 12 Months
timeFrame: 3, 6, and 12 months
Other outcomes:
Locations:
Study officials:
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