Clinical trial · Interventional
Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies
Pilot Study of Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies
NCT00856180CI-TRIAL-00034778completedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The goals of this study were to evaluate the efficacy and safety of sequentially blocking the angiogenesis pathway via known antiangiogenic mechanisms, first with bevacizumab and then addition of oral cyclophosphamide upon progression of cancer through bevacizumab. The drugs used in this study were chosen because of their known antiangiogenic properties, tolerability, and anti-ovarian cancer effects.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Fallopian Tube Cancer | Malignant Fallopian Tube Neoplasm | ALIAS | 0.90 |
| Ovarian Cancer | Malignant Ovarian Neoplasm | CURATED_EXACT | 0.92 |
| Peritoneal Cancer | Malignant Peritoneal Neoplasm | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Bevacizumab then Cyclophosphamide with Bevacizumab
- description
- Patients were given a regimen of sequential antiangiogenic blockade and disease assessed serologically and radiologically every 2 cycles/6 weeks. Patients started with bevacizumab 15 mg/kg IV every 3 weeks until they experienced progressive disease (PD) \[RECIST 1.0 or Rustin criteria\] or significant toxicity. If clinically stable as assessed by their treating physician, patients then received cyclophosphamide 50 mg orally (PO) daily continuously with bevacizumab treatment. If second PD occurred, patients discontinued the combination treatment.
- interventionNames
- Drug: Bevacizumab
- Drug: Cyclophosphamide
Primary outcomes (2)
- measure
- Therapy Completion Rate
- timeFrame
- Serologic and radiologic disease assessments occurred every 2 cycles/6 weeks on treatment. Median treatment duration for this study cohort was 7.5 months (range 0.7-20.7).
- description
- The therapy completion rate is defined as the proportion of participants who completed at least 3 months/4 cycles of therapy. Participants were treated until disease progression on the combination regimen or unacceptable toxicity. Clinical response was evaluated based on RECIST 1.0 criteria for measurable disease (MD) participants and Gynecologic Cancer Intergroup (GCIG) CA-125 (Rustin) criteria for non-MD participants. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Serologic PD is rise in CA-125 or previously normal CA125 that rises to \>/=2xULN documented, both requiring 2nd confirmation.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. * Recurrent cancer and have received and failed a previous platinum-based chemotherapy regimen. * Up to 2 prior lines of chemotherapy in the recurrent setting (either platinum-based or non-platinum regimens). Biologic therapies count as a prior line but hormonal therapies do not count. * Platinum-resistant or platinum-sensitive recurrence. * Must be able to take oral medications and have no evidence of bowel obstruction or partial bowel obstruction * Measurable disease by either RECIST or Rustin criteria * No chemotherapy, radiation therapy, nor biologic therapy within the last three weeks prior to initiating therapy * ECOG score of 0 or 1 * Life expectancy of 12 weeks or greater * 18 years of age or older * Laboratory values as outlined in the protocol * Patients 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 curative intent and no evidence of recurrent disease are also eligible. * No evidence of preexisting hypertension. If patient has hypertension, it must be controlled medically (less than 150/90) prior to starting bevacizumab * Normal blood coagulation parameters * No prior treatment with any other antiangiogenic agents or cyclophosphamide * For patients who have received prior doxorubicin or pegylated doxorubicin, LVEF must be 50% or greater. Exclusion Criteria: * Current, recent (within 4 weeks of the first study infusion), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study * Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years * Uncontrolled diarrhea * Prior history of hypertensive crisis or hypertensive encephalopathy * NYHA Grade II or greater congestive heart failure * History of myocardial infarction or unstable angina within 6 months prior to Day 1 * History of stroke or transient ischemic attack within 6 months prior to day 1 * Known CNS disease, except for treated brain metastasis * Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS: Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to day 1 will be excluded. * Significant vascular disease within 6 months prior to day 1 * History of hemoptysis within 1 month prior to day 1 * Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 or anticipation of need for major surgical procedure during the course of the study * Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 * History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 * Serious, non-healing wound, active ulcer, or untreated bone fracture * Proteinuria as demonstrated by a UPC ratio of 1.0 or greater at screening * Known hypersensitivity to any component of bevacizumab * Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
References
Publications (1)
- RESULTMatulonis UA, Pereira L, Liu J, Lee H, Lee J, Whalen C, Campos S, Atkinson T, Hill M, Berlin S. Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer. Gynecol Oncol. 2012 Jul;126(1):41-6. doi: 10.1016/j.ygyno.2012.04.003. Epub 2012 Apr 6. PMID 22487536