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CompletedNCT00868192Updated Oct 20, 2014Results posted

Trial of Pemetrexed and Bevacizumab for Recurrent Ovarian Primary Peritoneal Carcinoma

A Phase 2 interventional study of Pemetrexed and Bevacizumab in Ovarian Carcinoma and Primary Peritoneal Carcinoma, sponsored by Washington University School of Medicine. Completed at 1 site in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-10-20.

Sponsored by Washington University School of Medicine · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
38
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study summary

The purpose of this study is to determine if the combination of bevacizumab and pemetrexed have an effect on recurrent ovarian and primary peritoneal carcinoma by looking at progression and survival at 6 months.

Read the detailed description

Patients will be treated with pemetrexed 500 mg/m2 IV and Bevacizumab 15 mg/kg IV every 3 weeks.The patient is treated indefinitely until side effects are deemed severe by the investigator or until progression. Disease progression is measured every 6 weeks using RECIST criteria.

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Conditions studied

  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma

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03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 38 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

Washington University School of Medicine is the lead sponsor of 1,765 studies on the registry; 271 are open to participants now.

Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Recurrent epithelial ovarian or primary peritoneal carcinoma. Histologic confirmation of the primary tumor is required. Patients with borderline tumors are not eligible.
  • Patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in one dimension (longest dimension to be recorded). Each lesion must by > 20 mm when measured by conventional imaging techniques, including plain radiography, computed tomography and MRI or > 10 mm when measured by spiral CT.
  • Patients must have at least one "target lesion" to assess response by RECIST criteria. Lesions within a previously irradiated field will be considered "non-target" lesions.
  • Patients must have a GOG performance status of 0 or 1.
  • Patients must have the ability to interrupt non-steroidal anti-inflammatory (NSAID) treatment 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of pemetrexed.
  • Patients must have the ability to take folic acid, vitamin B12 and dexamethasone as described per protocol.
  • Recovery from effects of recent surgery, radiotherapy or chemotherapy.
  • Patients should be free of active infection requiring antibiotics.
  • Any hormonal therapy directed at the tumor must be discontinued at least one week prior to registration. Continuation of hormone replacement therapy (HRT) is permitted.
  • Any other prior therapy directed at the malignant tumor, including immunologic agents and cytotoxic agents, must be discontinued at least three weeks prior to registration.
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included high-dose therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment.
  • Patients must have had one prior regimen containing a taxane compound. Patient may have received first-line treatment either intravenously or intraperitoneally.
  • Patients must NOT have received prior therapy with pemetrexed or bevacizumab.
  • Patients may have received a total of \< 2 prior cytotoxic chemotherapy regimens (adjuvant therapy plus one additional regimen). Consolidation or extended therapy as part of first line treatment will be considered as a single regimen.
  • Bone marrow function: absolute neutrophil count (ANC) greater than or equal to 1,500/ul, equivalent to Common Toxicity Criteria (CTC) grade 1; Platelets greater than or equal to 100,000/ul.
  • Creatinine clearance must be greater than 45 ml/min.
  • Hepatic function: bilirubin less than or equal to 1.5 x ULN. AST and alkaline phosphatase less than or equal to 2.5 x ULN.
  • Neurologic function: neuropathy (sensory and motor) less than or equal to CTC grade 1.
  • Coagulation: prothrombin time (PT) such that the international normalized ratio (INR) is \< 1.5 (INR may be between 2 and 3 if a patient is on stable dose of therapeutic warfarin) and a PTT \< 1.2 times control.
  • Patients must have signed informed consent.
  • Patients must meet pre-entry requirements.
  • Patients of childbearing potential must have a negative serum pregnancy test prior to study entry, be practicing an effective form of contraception, and cannot be lactating.
  • Patients may have received prior radiotherapy (to less than 25% of bone marrow), but must start at a Level 1 dose reduction.

Exclusion criteria

Exclusion Criteria:

  • Patients with serious, non-healing wound, ulcer or bone fracture.
  • Patients with clinically significant cardiovascular disease:
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • Unstable angina within 6 months prior to study enrollment.
  • New York Heart Association (NYHA) grade II or greater congestive heart failure.
  • Serious cardiac arrhythmia requiring medication.
  • Grade II or greater peripheral vascular disease. Patients with claudication within 6 months.
  • History of myocardial infarction within 6 months.
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
  • Patients with the presence of ascites or other third space fluid which cannot be controlled by drainage.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of study or anticipation of need for major surgical procedure during the course of the study.
  • Patients with history or evidence upon physical examination of central nervous system disease, including primary brain tumor, brain metastases, seizure not controlled with standard medical therapy, history of cerebrovascular accident (CVA, stroke), or transient ischemic attack (TIA) or subarachnoid hemorrhage within 6 months of the first date of treatment on this study.
  • Minor surgical procedures, other than central venous access placement, such as fine needle aspiration or core biopsy within 7 days prior to day 1 of study.
  • Patients with proteinuria. At baseline patients will undergo a urine protein-creatinine ratio (UPCR) (Appendix IV). Patients with a UPCR > 1.0 at screening should be excluded. Urine dipstick for proteinuria may also be used. Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
  • Patients whose circumstances do not permit completion of the study or the required follow-up.
  • Patients who are pregnant or nursing.
  • Patients under the age of 18.
  • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of other cancer within the last 5 years or whose previous cancer treatment contraindicates this protocol.
  • Prior therapy with anti-angiogenic agents or pemetrexed.
  • Patients with active infection requiring parenteral antibiotics.
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months.
  • Partial or complete small or large bowel obstruction demonstrated radiographically within 3 months prior to study.
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study.
  • Known hypersensitivity to any component of bevacizumab.
  • Inability to comply with study and/or follow-up procedures.
  • Life expectancy of less than 12 weeks.
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Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
38 participants (actual)

Study arms

  • Experimental
    Pemetrexed and bevacizumab

    Pemetrexed 500 mg/m2 IV on Day 1 of each 21 day cycle Bevacizumab 15 mg/kg IV on Day 1 of each 21 day cycle

    Drug: Pemetrexed · Drug: Bevacizumab

Interventions

  • DrugPemetrexed

    Also known as: Alimta

  • DrugBevacizumab

    Also known as: Avastin

06

What researchers measure

Primary outcomes

  1. Progression-free Survival (PFS)

    PFS = Period from study entry until disease progression, death, or date of last contact

    Time frame: 6 months

Secondary outcomes

  1. Distribution of Progression-free Survival (PFS)

    PFS = Period from study entry until disease progression, death, or date of last contact

    Time frame: Median follow-up was 25.7 months (range 3.0-47.2 months)

  2. Distribution of Overall Survival (OS)

    OS = observed length of time from entry into the study to death or date of last contact

    Time frame: Median follow-up was 25.7 months (range 3.0-47.2 months)

  3. Toxicity Associated With Bevacizumab and Pemetrexed

    Detailed serious adverse events and other adverse events are shown in the adverse event module of the results.

    Time frame: 6 months

  4. Frequency of Clinical Response

    As measured by RECIST criteria

    Time frame: 6 months

  5. Gene Expression as Assessed by Illumina cDNA Mediated Annealing, Selection, Extension and Ligation (DASL) Microarray From Paraffin-embedded Tumor Specimens With Response to Pemetrexed and Bevacizumab

    Time frame: 6 months

  6. Association Between Levels of Thymidylate Synthase, Dihydrofolate Reductase, and Glycinamide Ribonucleotide Formyl Transferase and Ovarian Response to Pemetrexed and Bevacizumab

    Time frame: 6 months

07

Results

Posted Oct 20, 2014

Participant flow

The study was open to participant enrollment on 05/28/2008 and closed to participant enrollment on 11/30/2010.

Participant flow — Overall Study
MilestonePemetrexed and Bevacizumab
Started38
Completed34
Not completed4
Withdrew: Ineligible4

Outcome measures

PrimaryProgression-free Survival (PFS)

PFS = Period from study entry until disease progression, death, or date of last contact

Time frame:
6 months
Reported as:
Number · percentage of participants
Progression-free Survival (PFS)
percentage of participantsPemetrexed and Bevacizumab
Progression-free Survival (PFS)56 (38 to 71)
SecondaryDistribution of Progression-free Survival (PFS)

PFS = Period from study entry until disease progression, death, or date of last contact

Time frame:
Median follow-up was 25.7 months (range 3.0-47.2 months)
Reported as:
Median · months
Distribution of Progression-free Survival (PFS)
monthsPemetrexed and Bevacizumab
Platinum-free interval of <6 months6.7 (4.1 to 9.9)
Platinum-free interval of 6-12 months4.7 (2.8 to 8.4)
Platinum-free interval of >12 months16.8 (4.6 to 23.2)
SecondaryDistribution of Overall Survival (OS)

OS = observed length of time from entry into the study to death or date of last contact

Time frame:
Median follow-up was 25.7 months (range 3.0-47.2 months)
Reported as:
Median · months
Distribution of Overall Survival (OS)
monthsPemetrexed and Bevacizumab
Platinum-free interval of <6 months16.7 (7.5 to 33.4)
Platinum-free interval of 6-12 months24.9 (6.2 to 28.6)
Platinum-free interval of >12 months28.0 (6.0 to NA)
SecondaryToxicity Associated With Bevacizumab and Pemetrexed

Detailed serious adverse events and other adverse events are shown in the adverse event module of the results.

Time frame:
6 months
Reported as:
Number · percentage of participants
Toxicity Associated With Bevacizumab and Pemetrexed
percentage of participantsPemetrexed and Bevacizumab
Grade 3/4 hematologic toxicity53
Most common non-hematologic toxicity - fatigue94
Grade 3 renal toxicity6
Gastrointestinal toxicity91
Subsequently developed hematologic malignancies6
SecondaryFrequency of Clinical Response

As measured by RECIST criteria

Time frame:
6 months
Reported as:
Number · participants
Frequency of Clinical Response
participantsPemetrexed and Bevacizumab
Complete response0
Partial response14
Stable disease18
Progressive disease2
SecondaryGene Expression as Assessed by Illumina cDNA Mediated Annealing, Selection, Extension and Ligation (DASL) Microarray From Paraffin-embedded Tumor Specimens With Response to Pemetrexed and Bevacizumab
Time frame:
6 months

No measurements were reported for this outcome.

SecondaryAssociation Between Levels of Thymidylate Synthase, Dihydrofolate Reductase, and Glycinamide Ribonucleotide Formyl Transferase and Ovarian Response to Pemetrexed and Bevacizumab
Time frame:
6 months

No measurements were reported for this outcome.

Post-hocOverall Survival (OS)

OS = observed length of time from entry into the study to death or date of last contact

Time frame:
12 months
Reported as:
Number · percentage of participants
Overall Survival (OS)
percentage of participantsPemetrexed and Bevacizumab
Overall Survival (OS)79 (62 to 90)
Post-hocProgression-free Survival (PFS)

PFS = Period from study entry until disease progression, death, or date of last contact

Time frame:
Median follow-up was 25.7 months (range 3.0-47.2 months)
Reported as:
Median · months
Progression-free Survival (PFS)
monthsPemetrexed and Bevacizumab
Progression-free Survival (PFS)7.9 (4.6 to 10.9)
Post-hocOverall Survival (OS)

OS = observed length of time from entry into the study to death or date of last contact

Time frame:
Median follow-up was 25.7 months (range 3.0-47.2 months)
Reported as:
Median · months
Overall Survival (OS)
monthsPemetrexed and Bevacizumab
Overall Survival (OS)25.7 (15.4 to 29.8)
Post-hocOverall Response Rate

Overall response rate = complete response + partial response Complete response = disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response = at least a 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be non unequivocal progression of non-target lesions and no new lesions.

Time frame:
6 months
Reported as:
Number · percentage of participants
Overall Response Rate
percentage of participantsPemetrexed and Bevacizumab
Overall Response Rate41 (25 to 59)
Post-hocCA-125 Response

A CA-125 response was defined as at least a 50% reduction in CA-125 levels from a pretreatment sample following guidelines described by the Gynecological Cancer Intergroup.

Time frame:
6 months
Reported as:
Number · participants
CA-125 Response
participantsPemetrexed and Bevacizumab
50% CA-125 response17
75% CA-125 response8
No CA-125 response2

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pemetrexed and Bevacizumab—5/34 (14.7%)34/34 (100%)
Most frequent serious events
Most frequent serious events
EventPemetrexed and Bevacizumab
VomitingGastrointestinal disorders2/34
NauseaGastrointestinal disorders1/34
Small bowel obstructionGastrointestinal disorders1/34
Thromobolic eventVascular disorders1/34
Septic embolismVascular disorders1/34
Most frequent other events
Showing 10 of 23
Most frequent other events
EventPemetrexed and Bevacizumab
NeutropeniaInvestigations33/34
ConstitutionalGeneral disorders32/34
MetabolicMetabolism and nutrition disorders31/34
PainGeneral disorders29/34
AnemiaBlood and lymphatic system disorders28/34
LeukopeniaInvestigations28/34
GastrointestinalGastrointestinal disorders27/34
RashSkin and subcutaneous tissue disorders23/34
NeurologicNervous system disorders21/34
PulmonaryRespiratory, thoracic and mediastinal disorders16/34

Baseline characteristics

Age, Continuous
Age, Continuous(years)Pemetrexed and Bevacizumab
Mean61.5 (31 to 86)
Sex: Female, Male
Sex: Female, Male(Participants)Pemetrexed and Bevacizumab
Female34
Male0
Region of Enrollment
Region of Enrollment(participants)Pemetrexed and Bevacizumab
United States34
Stage
Stage(participants)Pemetrexed and Bevacizumab
Stage I/II1
Stage III27
Stage IV6
Histology
Histology(participants)Pemetrexed and Bevacizumab
Serous24
Endometriod2
Mixed3
Other5
Tumor grade
Tumor grade(participants)Pemetrexed and Bevacizumab
Grade 13
Grade 21
Grade 330
Pathologic diagnosis
Pathologic diagnosis(participants)Pemetrexed and Bevacizumab
Ovarian27
Fallopian tube1
Primary peritoneal6
Gynecologic Oncology Group (GOG) Performance Status
Gynecologic Oncology Group (GOG) Performance Status(participants)Pemetrexed and Bevacizumab
022
112

2 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Washington University School of Medicine
    St. Louis, Missouri 63110, United States
09

References and documents

Publications

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 20, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00868192
Lead sponsor
Washington University School of Medicine
Collaborators
Columbia University
Responsible party
Sponsor
First posted
Mar 24, 2009
Start date
May 2008
Primary completion
Dec 2012
Completion
Dec 2012
Results posted
Oct 20, 2014
Last update
Oct 20, 2014

Study contacts

David G Mutch, M.D.
principal investigator · Washington University School of Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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