A Phase 1/2 interventional study of bevacizumab and carboplatin in Lung Cancer, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 3 sites in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2017-06-19.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 1/2, Interventional, and Treatment
RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 non-small cell lung cancer by blocking blood flow to the tumor. Radiation therapy uses high energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with bevacizumab, radiation therapy, and erlotinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of bevacizumab and erlotinib when given together with combination chemotherapy and radiation therapy and to see how well they work in treating patients with stage III non-small cell lung cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a nonrandomized, open-label, controlled, phase I (closed to accrual as of 1/3/2008), dose-escalation study of bevacizumab and erlotinib hydrochloride, followed by a phase II study.
Phase I (closed to accrual as of 1/3/2008):
Chemoradiotherapy: Patients receive chemoradiotherapy according to their assigned dose cohort:
Cohorts of 5 patients receive chemoradiotherapy as described above until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 (with grade 4 toxicity) or 3 (with grade 3 toxicity) of 5 patients experience dose-limiting toxicity.
Three to 6 weeks after completion of chemoradiotherapy, patients proceed to consolidation therapy.
Consolidation therapy: Patients receive bevacizumab IV on day 1 and oral erlotinib hydrochloride on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Tumor tissue and peripheral blood is collected at baseline for future correlative and biomarker studies.
After completion of study therapy, patients are followed every 2 months for 2 years, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.
7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.
This study's enrollment of 46 is below the median of 60 across 5,295 interventional studies indexed under Lung Neoplasms.
Browse Lung Neoplasms studies →UNC Lineberger Comprehensive Cancer Center is the lead sponsor of 414 studies on the registry; 96 are open to participants now.
Of its 32 completed or terminated interventional studies of FDA-regulated products, 25 (78%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Diagnosis of non-small cell lung cancer
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Bevacizumab 10 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)
Biological: bevacizumab · Drug: carboplatin · Drug: paclitaxel · Radiation: 3-dimensional conformal radiation therapy
Bevacizumab 10 mg + Erlotinib 100 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)
Biological: bevacizumab · Drug: carboplatin · Drug: erlotinib hydrochloride · Drug: paclitaxel · Radiation: 3-dimensional conformal radiation therapy
Bevacizumab + Erlotinib 150 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)
Biological: bevacizumab · Drug: carboplatin · Drug: erlotinib hydrochloride · Drug: paclitaxel · Radiation: 3-dimensional conformal radiation therapy
Bevacizumab + Erlotinib 100 mg + Chemoradiotherapy (carboplatin, paclitaxel, and 3-dimensional conformal radiation therapy)
Biological: bevacizumab · Drug: carboplatin · Drug: erlotinib hydrochloride · Drug: paclitaxel · Radiation: 3-dimensional conformal radiation therapy
Given IV
Given IV
Given orally
Given IV
Given 5 days a week for 7 weeks
Maximum Dose of Erlotinib When Given Together With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy (Phase I [Closed to Accrual as of 1/3/2008])
Dose-limiting toxicities (DLTs) were used to establish which cohort would be used for the phase II portion of the trial. DLTs were defined as any grade 3 or 4 nonhematologic toxicity with the exception of esophagitis, which had to be grade 4; grade 4 neutropenia lasting greater than or equal to 7 days and thrombocytopenia to less than 20,000/microliter.
Time frame: 6 weeks after completion of therapy
Safety and Toxicity Profile of Combining Both Bevacizumab and Erlotinib Hydrochloride With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy
A list of Hematologic and nonhematologic toxicities associated with induction and concurrent therapy. This includes the percentage of patients who experienced grades 2-4 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0).
Time frame: 6 weeks after completion of therapy
Progression-free Survival (PFS)
The length of time during and after the treatment of a stage IIIA/B NSCLC that a patient lives with the disease but it does not get worse. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: 5 years
Response Rate to Induction Therapy (Phase I [Closed to Accrual as of 1/3/2008] and II)
Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement. The same method of assessment and the same techniques should be used to characterize each identified and reported lesion at baseline and during follow-up. Complete Response (CR)- Disappearance of all target lesions
Time frame: 5 years
Overall Response Rate and Survival Profile
The overall response rate (ORR) to the two cycles of induction therapy plus bevacizumab in stage IIIA/B NSCLC. ORR is the portion of patients with a tumor size reduction for a minimum time period. Response duration is measured from the time of initial response until documented tumor progression.
Time frame: 5 years
Feasibility and Tolerability of Administering Consolidation Therapy
The proportion of patients who were able to complete consolidation therapy after induction therapy and chemoradiotherapy
Time frame: 6 cycles
Participants were recruited from four institutions between February 2006 and April 2010.
| Milestone | Cohort 1 | Cohort 2 | Cohort 3 | Phase II |
|---|---|---|---|---|
| Started | 5 | 5 | 6 | 30 |
| Cohort induction | 5 | 5 | 6 | 30 |
| Consolidation therapy | 2 | 5 | 3 | 0 |
| Completed | 2 | 4 | 1 | 20 |
| Not completed | 3 | 1 | 5 | 10 |
| Withdrew: Adverse event | 0 | 1 | 2 | 3 |
| Withdrew: Lack of efficacy | 0 | 0 | 0 | 3 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 |
| Withdrew: Protocol violation | 0 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 1 |
| Withdrew: Did not get consolidation therapy | 3 | 0 | 3 | 0 |
| Withdrew: Declining performance status | 0 | 0 | 0 | 1 |
Dose-limiting toxicities (DLTs) were used to establish which cohort would be used for the phase II portion of the trial. DLTs were defined as any grade 3 or 4 nonhematologic toxicity with the exception of esophagitis, which had to be grade 4; grade 4 neutropenia lasting greater than or equal to 7 days and thrombocytopenia to less than 20,000/microliter.
| DLTs | Cohort 1 | Cohort 2 | Cohort 3 | Phase II |
|---|---|---|---|---|
| Maximum Dose of Erlotinib When Given Together With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy (Phase I [Closed to Accrual as of 1/3/2008]) | 0 | 0 | 2 | — |
A list of Hematologic and nonhematologic toxicities associated with induction and concurrent therapy. This includes the percentage of patients who experienced grades 2-4 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0).
| percentage of participants | Induction Therapy | Concurrent Therapy |
|---|---|---|
| Anemia | 4 | 17 |
| Neutrophenia | 52 | 35 |
| Thrombocytopenia | 0 | 16 |
| Febrile neutropenia | 0 | 2 |
| Nausea/vomiting | 7 | 6 |
| Fatigue | 20 | 22 |
| Alopecia | 42 | 9 |
| Hypertension | 9 | 4 |
| Myalgias/arthralgias | 27 | 0 |
| Diarrhea | 6 | 2 |
| Neuropathy | 2 | 2 |
| Rash | 2 | 11 |
| Anorexia | 0 | 6 |
| Esophagitis | 0 | 40 |
| Dehydration | 0 | 11 |
| Hemorrhage | 0 | 6 |
| Hypomagnesemia | 0 | 4 |
| Proteinuria | 0 | 2 |
| Weight loss | 0 | 9 |
| Pneumonitis | 0 | 2 |
| Hypersensitivity reaction | 4 | 2 |
The length of time during and after the treatment of a stage IIIA/B NSCLC that a patient lives with the disease but it does not get worse. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
| Months | Overall Study |
|---|---|
| Progression-free Survival (PFS) | 10.2 (8.4 to 18.3) |
Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \> 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement. The same method of assessment and the same techniques should be used to characterize each identified and reported lesion at baseline and during follow-up. Complete Response (CR)- Disappearance of all target lesions
| Participants | Overall Study |
|---|---|
| Response Rate to Induction Therapy (Phase I [Closed to Accrual as of 1/3/2008] and II) | 0 |
The overall response rate (ORR) to the two cycles of induction therapy plus bevacizumab in stage IIIA/B NSCLC. ORR is the portion of patients with a tumor size reduction for a minimum time period. Response duration is measured from the time of initial response until documented tumor progression.
| percentage of participants | Overall Study |
|---|---|
| Overall Response Rate and Survival Profile | 39 (24 to 55) |
The proportion of patients who were able to complete consolidation therapy after induction therapy and chemoradiotherapy
| Participants | Overall Study |
|---|---|
| Feasibility and Tolerability of Administering Consolidation Therapy | 5 |
Collected over 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Overall Study | 30/45 (66.7%) | 19/45 (42.2%) | 45/45 (100%) |
| Event | Overall Study |
|---|---|
| EsophagitisGastrointestinal disorders | 5/45 |
| DehydrationMetabolism and nutrition disorders | 2/45 |
| Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infeBlood and lymphatic system disorders | 2/45 |
| Infection with unknown ANC - EsophagusInfections and infestations | 2/45 |
| EsophagitisGastrointestinal disorders | 1/45 |
| Hemorrhage, pulmonary/upper respiratory - BronchusRespiratory, thoracic and mediastinal disorders | 1/45 |
| Hemorrhage/Bleeding - Other (Specify, __)Vascular disorders | 1/45 |
| Pain - Chest/thorax NOSGeneral disorders | 1/45 |
| DiarrheaGastrointestinal disorders | 1/45 |
| DizzinessNervous system disorders | 1/45 |
| Event | Overall Study |
|---|---|
| Hair loss/alopecia (scalp or body)Skin and subcutaneous tissue disorders | 35/45 |
| Fatigue (asthenia, lethargy, malaise)General disorders | 34/45 |
| Neutrophils/granulocytes (ANC/AGC)Investigations | 34/45 |
| EsophagitisGastrointestinal disorders | 27/45 |
| Pain - JointMusculoskeletal and connective tissue disorders | 24/45 |
| HemoglobinBlood and lymphatic system disorders | 22/45 |
| Neuropathy: sensoryNervous system disorders | 21/45 |
| PlateletsInvestigations | 20/45 |
| DiarrheaGastrointestinal disorders | 18/45 |
| NauseaGastrointestinal disorders | 18/45 |
| Age, Categorical(Participants) | Cohort 1 | Cohort 2 | Cohort 3 | Phase II | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 3 | 3 | 18 | 28 |
| >=65 years | 1 | 2 | 3 | 12 | 18 |
| Sex: Female, Male(Participants) | Cohort 1 | Cohort 2 | Cohort 3 | Phase II | Total |
|---|---|---|---|---|---|
| Female | 1 | 2 | 3 | 16 | 22 |
| Male | 4 | 3 | 3 | 14 | 24 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1 | Cohort 2 | Cohort 3 | Phase II | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 1 | 1 |
| Not Hispanic or Latino | 5 | 5 | 6 | 29 | 45 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort 1 | Cohort 2 | Cohort 3 | Phase II | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 1 | 0 | 0 | 1 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 2 | 7 | 10 |
| White | 4 | 4 | 4 | 22 | 34 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Cohort 1 | Cohort 2 | Cohort 3 | Phase II | Total |
|---|---|---|---|---|---|
| United States | 5 | 5 | 6 | 30 | 46 |
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