Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies

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• Neoplasms 9,365
• Fallopian Tube Neoplasms 720

Keywords

• avastin
• bevacizumab
• cyclophosphamide
• cytoxan
• mullerian malignancies

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 20 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Study arms

• Experimental
  Bevacizumab then Cyclophosphamide with Bevacizumab

  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.

  Drug: Bevacizumab · Drug: Cyclophosphamide

Interventions

• DrugBevacizumab

  Also known as: Avastin

• DrugCyclophosphamide

  Also known as: cytoxan

Primary outcomes

1. Therapy Completion Rate

   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.

   Time frame: 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).

2. Grade 3-5 Gastrointestinal Perforation

   All grade 3-5 gastrointestinal perforation events based on CTCAEv3 as reported on case report forms.

   Time frame: Assessed each cycle/3 weeks throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort was 7.5 months (range 0.7-20.7).

Secondary outcomes

1. Clinical Benefit Response Rate

   Clinical benefit response rate is defined as the proportion of participants who achieve confirmed stable disease (SD) or better on treatment based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (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. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

   Time frame: 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).

2. Progression-Free Survival (PFS)

   PFS estimated using Kaplan-Meier methods is defined as the duration of time from the start of bevacizumab alone to documented disease progression (PD) requiring removal from the study or death. If participant ultimately received both bevacizumab and cyclophosphamide then it was the time until PD on both agents. 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 CA-125 that rises to \>/=2xULN documented, both requiring 2nd confirmation. Participants who were event-free were censored at the date of their last disease evaluation.

   Time frame: Radiologic disease assessments occurred every 2 cycles/6 weeks on treatment and every 3 months in follow-up until PD, death or lost to follow-up. Median treatment duration was 7.5 months (range 0.7-20.7) and survival follow-up 23 months..

3. Overall Survival (OS)

   OS estimated using Kaplan-Meier methods is defined as the time from study entry to death or date last known alive.

   Time frame: Participants were followed long-term for survival every 3 months from the end of treatment until death or lost to follow-up. Median follow-up was 23 months in this study cohort.

Baseline characteristics

Publications

• Matulonis 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. PubMed 22487536 ↗

Individual participant data

Plan to share: No