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NCT00408694

Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

Completed Phase 2 Results posted Last updated 30 January 2018
What this trial tests

Phase 2 trial testing 3-Dimensional Conformal Radiation Therapy in Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 in 46 participants. Completed in 15 December 2011.

Timeline
13 December 2006
Primary endpoint
15 December 2011
15 December 2011

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment46
Start date13 December 2006
Primary completion15 December 2011
Estimated completion15 December 2011
Sites108 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 or Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Patients With a Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment During the First Year. Primary · From start of treatment to one year.

Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)00 – 0
Percentage of Patients With Grade 4 Hemorrhage or Any Grade 5 Adverse Event Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment After the First Year. Secondary · Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from day 366 to death or study termination whichever occurs first, up to 3.6 years.

Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)00 – 0
Patient Tolerability to Each Component (Concurrent and Adjuvant) of the Protocol Treatment Regimen Secondary · From start of treatment to end of treatment (approximately day 109).

Evaluated in terms of protocol treatment delivery. For concurrent treatment, measured by the percentage of patients who received 2 or more cycles of cisplatin (CDDP) and bevacizumab (BV) during concurrent treatment with radiation therapy(RT) and who had RT scored by the study chair as no variation or minor variation. For adjuvant treatment, measured by the percentage of patients who received 2 or more cycles of CDDP and 5-FU and BV during the adjuvant treatment phase. Estimated using a binomial distribution along with their associated 95% confidence intervals.

Concurrent component
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)68.252.4 – 81.4
Adjuvant component
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)68.252.4 – 81.4
Death During or Within 30 Days of Discontinuation of Protocol Treatment. Secondary · From start of treatment to 30 days after end of treatment (treatment ends approximately day 109).

The percentage of patients dying during protocol treatment or within 30 days after the end of treatment. Estimated using a binomial distribution along with associated 95% confidence interval.

GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)00 – 0
One- and Two-year Distant Metastases-free Rates Secondary · From registration to two years

Distant metastasis is defined as clear evidence of distant metastases (lung, bone, brain, etc.); biopsy is recommended where possible. Distant metastasis-free rate estimated by cumulative incidence method with death considered a competing risk.

One-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)97.793.3 – 100.0
Two-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)90.882.2 – 99.5
One- and Two-year Loco-regional Progression-free Rates Secondary · Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.

Loco-regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Local-regional progression-free rate estimated by cumulative incidence with death considered a competing risk.

One-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)93.285.6 – 100.0
Two-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)74.761.8 – 87.6
One- and Two-year Progression-free Survival Rates Secondary · Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.

Progression-free survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is loco-regional or distant progression, or death due to any cause. Loco-regional progression is defined as an estimated increase in the size of the tumor (product of the perpendicular diameters of the two largest dimensions) of greater than 25%, taking as reference the smallest value of all previous measurements or appearance of new areas of malignant disease. Distant progression is defined as distant metastases.

One-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)90.982.4 – 99.4
Two-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)74.761.8 – 87.6
One- and Two-year Overall Survival Rates Secondary · Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from study registration to death or study termination whichever occurs first, up to 3.6 years.

Overall survival rate estimated by Kaplan-Meier method along with 95% confidence interval. An event is death due to any cause.

One-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)93.285.7 – 100.0
Two-year
GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)90.982.3 – 99.4
Percentage of Patients With Other Grade 3-5 Adverse Events Assessed to be Definitely, Probably, or Possibly Related to Protocol Treatment Secondary · Analysis occurs after all patients have been on study for at least 2 years. Patients are followed from start of treatment to death or study termination whichever occurs first, up to 3.6 years.

Estimated using a binomial distribution along with the 95% confidence interval. Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

GroupValue95% CI
Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)90.978.3 – 97.5

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Bevacizumab, Cisplatin, Fluorouracil, IMRT, 3D-CRT)
Serious: 28/44 (64%)
Deaths:

Serious adverse events (61 terms)

ReactionSystemTreatment (Bevacizumab, Ci…
Mucositis oralGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
DysphagiaGastrointestinal disorders
Neutrophil count decreasedInvestigations
FatigueGeneral disorders
Infections and infestations - OtherInfections and infestations
White blood cell decreasedInvestigations
Platelet count decreasedInvestigations
DepressionPsychiatric disorders
Hearing impairedEar and labyrinth disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
HyponatremiaMetabolism and nutrition disorders
Depressed level of consciousnessNervous system disorders
Pharyngeal mucositisRespiratory, thoracic and mediastinal disorders
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
AnemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Oral painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Other adverse events (151 terms — click to expand)

ReactionSystemTreatment (Bevacizumab, Ci…
Dry mouthGastrointestinal disorders
DysphagiaGastrointestinal disorders
Mucositis oralGastrointestinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
Peripheral sensory neuropathyNervous system disorders
Pharyngeal mucositisRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
ConstipationGastrointestinal disorders
Dermatitis radiationInjury, poisoning and procedural complications
VomitingGastrointestinal disorders
Hearing impairedEar and labyrinth disorders
Radiation recall reaction (dermatologic)Injury, poisoning and procedural complications
Skin indurationSkin and subcutaneous tissue disorders
Weight lossInvestigations
AnemiaBlood and lymphatic system disorders
White blood cell decreasedInvestigations
NeuralgiaNervous system disorders
HyponatremiaMetabolism and nutrition disorders
TrismusMusculoskeletal and connective tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
TinnitusEar and labyrinth disorders
Oral painGastrointestinal disorders
Neutrophil count decreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
Platelet count decreasedInvestigations
Voice alterationRespiratory, thoracic and mediastinal disorders
AnorexiaMetabolism and nutrition disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders
FeverGeneral disorders
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
Edema faceGeneral disorders
DehydrationMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Laryngeal edemaRespiratory, thoracic and mediastinal disorders
PainGeneral disorders
Lymphocyte count decreasedInvestigations

Most-reported serious reactions: Mucositis oral, Dehydration, Nausea, Vomiting, Dysphagia, Neutrophil count decreased, Fatigue, Infections and infestations - Other.

Data from ClinicalTrials.gov NCT00408694 adverse events section.

Sponsor's own description

This phase II trial is studying how well giving bevacizumab together with cisplatin, radiation therapy, and fluorouracil works in treating patients with stage IIB, stage III, stage IVA, or stage IVB nasopharyngeal cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of nasopharyngeal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with chemotherapy and radiation therapy may kill more tumor cells.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial.
    Lee NY, Zhang Q, Pfister DG, Kim J, et al · · 2012 · cited 268× · PMID 22178121 · DOI 10.1016/s1470-2045(11)70303-5
  2. Targeting the signaling in Epstein-Barr virus-associated diseases: mechanism, regulation, and clinical study.
    Cao Y, Xie L, Shi F, Tang M, et al · · 2021 · cited 86× · PMID 33436584 · DOI 10.1038/s41392-020-00376-4
  3. Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses - Pre-Clinical Evidence and Ongoing Clinical Applications.
    Derer A, Deloch L, Rubner Y, Fietkau R, et al · · 2015 · cited 77× · PMID 26500646 · DOI 10.3389/fimmu.2015.00505
  4. Nasopharyngeal Carcinoma and Its Microenvironment: Past, Current, and Future Perspectives.
    Su ZY, Siak PY, Leong CO, Cheah SC. · · 2022 · cited 32× · PMID 35311066 · DOI 10.3389/fonc.2022.840467
  5. The clinical application of angiostatic therapy in combination with radiotherapy: past, present, future.
    Hamming LC, Slotman BJ, Verheul HMW, Thijssen VL. · · 2017 · cited 26× · PMID 28364160 · DOI 10.1007/s10456-017-9546-9
  6. Reflecting on the utility of standardized uptake values on <sup>18</sup>F-FDG PET in nasopharyngeal carcinoma.
    Qiu X, Wu H, Xu T, Xie S, et al · · 2022 · cited 6× · PMID 35513804 · DOI 10.1186/s12885-022-09626-w
  7. Long-term Outcomes of Bevacizumab and Chemoradiation for Locoregionally Advanced Nasopharyngeal Carcinoma: A Nonrandomized Controlled Trial.
    Lee NY, Harris J, Kim J, Garden A, et al · · 2023 · cited 4× · PMID 37266942 · DOI 10.1001/jamanetworkopen.2023.16094

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00408694.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing