Trial Outcomes & Findings for Phase I/II Trial of Bevacizumab, Pemetrexed and Erlotinib in Elderly Patients With Non-Small Cell Lung Cancer (NCT NCT00351039)

Last Updated: 2017-03-23

Results Overview

The primary objective was to determine the progression free survival (PFS), in newly diagnosed patients with advanced Non Small Cell Lung Cancer (NSCLC) who are treated with a regimen consisting of Bevacizumab(B), pemetrexed(A), and erlotnib(T). This was a Phase I/II study. This trial was halted after the Phase I component was completed. The Phase II component was never initiated.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

26 months

Results posted on

2017-03-23

Participant Flow

July 2006 through September 2008 at Moffitt Cancer Center

Phase I run-in. One participant was excluded due to screen failure, showing that they should not have been included to start.

Participant milestones

Participant milestones
Measure	Experimental: Bevacizumab, Erlotinib, Pemetrexed Treatment Regimen Item 1: Bevacizumab 10mg/Kg I. V. Day 1 and Day 15. Repeat cycles every 28 days. Treatment Regimen Item 2: Erlotinib(Tarceva™) 150mg Per Orally (PO) Once Daily (QD) for 7 days starting day 2 and day 15. Repeat cycles every 28 days. Treatment Regimen Item 3: Pemetrexed(Alimta™) 500mg/m2 I.V. Day 1 and Day 15. Repeat cycles every 28 days. The regimen then was modified to the following dose: Bevacizumab 15mg/kg Day 1 every 21 days (Q21); Pemetrexed 500 mg/m2 Day 1 Q 21; Erlotinib 150 mg QD PO Day 2 to day 15 (Both days inclusive). This dose was then recommended to be Phase II dose.
Overall Study STARTED	8
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I/II Trial of Bevacizumab, Pemetrexed and Erlotinib in Elderly Patients With Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Bevacizumab, Erlotinib, Pemetrexed n=8 Participants Treatment Regimen Item 1: Bevacizumab 10mg/Kg I. V. Day 1 and Day 15. Repeat cycles every 28 days. Treatment Regimen Item 2: Erlotinib(Tarceva™) 150mg Per Orally (PO) Once Daily (QD) for 7 days starting day 2 and day 15. Repeat cycles every 28 days. Treatment Regimen Item 3: Pemetrexed(Alimta™) 500mg/m2 I.V. Day 1 and Day 15. Repeat cycles every 28 days. The regimen then was modified to the following dose: Bevacizumab 15mg/kg Day 1 every 21 days (Q21); Pemetrexed 500 mg/m2 Day 1 Q 21; Erlotinib 150 mg QD PO Day 2 to day 15 (Both days inclusive). This dose was then recommended to be Phase II dose.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=99 Participants
Age, Categorical >=65 years	8 Participants n=99 Participants
Age, Continuous	75 years STANDARD_DEVIATION 5 • n=99 Participants
Sex: Female, Male Female	5 Participants n=99 Participants
Sex: Female, Male Male	3 Participants n=99 Participants
Region of Enrollment United States	8 participants n=99 Participants
Number of Participants who received treatment on this protocol	8 Participants n=99 Participants

PRIMARY outcome

Timeframe: 26 months

Population: No patients proceeded to Phase II for evaluation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 26 Months

Population: Had the study been completed as planned we would have measured the One-year Survival. This study was closed early due to poor accrual.

Secondary Objective: One-year survival(1-year S) in patients with advanced NSCLC treated with this regimen.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 26 Months

Population: 8 patients were accrued to the Phase I component of the trial. No patients were accrued to the Phase II component of the trial.

Phase I: Response Evaluation Criteria In Solid Tumors (RECIST)Criteria was used for Response. Partial Response (PR) is defined as at least a 30% decrease in the sum of Longest Dimention (LD) of target lesions taking as reference the baseline sum LD.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 26 Months

Population: Since no patients were accrued to the Phase II component of the trial, 0 patients were analyzed for these scales.

The Scales we were intending to use were: Instrumental Activities of Daily Living (IADL): Range of Scale 0 (Best) to 8 (Worst). Cumulative Illness Rating Scale-Geriatric (CIRS-G): Range of Scores 1(Best) to 18 (Worst). Functional Assessment of Cancer Therapy-Lung (FACT-L): Range of Scores 0 (Best) to 48 (Worst). Fatigue Symptom Inventory (FSI): Range of Scores 0(Best) to 121 (Worst). Each scale would have been evaluated independently. Since the study was not completed and closed early due to poor accrual, none of the QOL parameters were analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 26 Months

Population: This study was initially intended to be a Phase I/II study with a brief Phase I Run-in. After the brief Phase I Run-in the study was closed without initiating the Phase II component.

By Safety, the intent was to capture, tabulate, list all of the grade 3 and 4 adverse effects seen by this protocol. For each toxicity, we followed the Common Toxicity Criteria(NCI CTC)Version 2.0 Toxicity scale guidelines.

Outcome measures

Outcome measures
Measure	Experimental: Bevacizumab, Erlotinib, Pemetrexed n=8 Participants Treatment Regimen Item 1: Bevacizumab 10mg/Kg I. V. Day 1 and Day 15. Repeat cycles every 28 days. Treatment Regimen Item 2: Erlotinib(Tarceva™) 150mg PO QD for 7 days starting day 2 and day 15. Repeat cycles every 28 days. Treatment Regimen Item 3: Pemetrexed(Alimta™) 500mg/m2 I.V. Day 1 and Day 15. Repeat cycles every 28 days. The regimen then was modified to the following dose: Bevacizumab 15mg/kg Day 1 Q21 Pemetrexed 500 mg/m2 Day 1 Q 21 Erlotinib 150 mg QD PO Day 2 to day 15 (Both days inclusive) This dose was then recommended to be phase II dose.
Number of Participants With Grade 3 and Grade 4 Adverse Events	8 Participants

SECONDARY outcome

Timeframe: 26 Months

Population: Had the study been completed as planned we would have measured Overall Survival described as Median Survival. This study was closed early due to poor accrual.

Secondary Objective: Determine the Overall Survival (median survival\[MS\]) in patients with advanced NSCLC treated with this regimen. Patients were to be followed until death and survival curves were to be generated.

Outcome measures

Outcome data not reported

Adverse Events

Experimental: Bevacizumab, Erlotinib, Pemetrexed

Serious events: 6 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental: Bevacizumab, Erlotinib, Pemetrexed n=8 participants at risk Treatment Regimen Item 1: Bevacizumab 10mg/Kg I. V. Day 1 and Day 15. Repeat cycles every 28 days. Treatment Regimen Item 2: Erlotinib(Tarceva™) 150mg Per Orally (PO) Once Daily (QD) for 7 days starting day 2 and day 15. Repeat cycles every 28 days. Treatment Regimen Item 3: Pemetrexed(Alimta™) 500mg/m2 I.V. Day 1 and Day 15. Repeat cycles every 28 days. The regimen then was modified to the following dose: Bevacizumab 15mg/kg Day 1 every 21 days (Q21); Pemetrexed 500 mg/m2 Day 1 Q 21; Erlotinib 150 mg QD PO Day 2 to day 15 (Both days inclusive). This dose was then recommended to be Phase II dose.
Respiratory, thoracic and mediastinal disorders Syncope	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Non Febrile Neutropenia	25.0% 2/8 • Number of events 2 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Fatigue	37.5% 3/8 • Number of events 3 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Dyspnea with exertion	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Proteinuria	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Hemorrhage	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Hyperglycemia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Pain, Penis	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Secondary Malignancy (bladder tumor)	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Right Hip Pain	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Dehydration	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Anorexia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Hypokalemia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.

Other adverse events

Other adverse events
Measure	Experimental: Bevacizumab, Erlotinib, Pemetrexed n=8 participants at risk Treatment Regimen Item 1: Bevacizumab 10mg/Kg I. V. Day 1 and Day 15. Repeat cycles every 28 days. Treatment Regimen Item 2: Erlotinib(Tarceva™) 150mg Per Orally (PO) Once Daily (QD) for 7 days starting day 2 and day 15. Repeat cycles every 28 days. Treatment Regimen Item 3: Pemetrexed(Alimta™) 500mg/m2 I.V. Day 1 and Day 15. Repeat cycles every 28 days. The regimen then was modified to the following dose: Bevacizumab 15mg/kg Day 1 every 21 days (Q21); Pemetrexed 500 mg/m2 Day 1 Q 21; Erlotinib 150 mg QD PO Day 2 to day 15 (Both days inclusive). This dose was then recommended to be Phase II dose.
Respiratory, thoracic and mediastinal disorders Pruritis	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Fatigue	37.5% 3/8 • Number of events 3 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Mucositis	25.0% 2/8 • Number of events 2 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Anemia	25.0% 2/8 • Number of events 2 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Generalized Weakness	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Nausea	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Vomiting	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Expressive Aphasia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Neutropenia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Serum Creatinine Elevation	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders ALT Elevation	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Non Febrile Neutropenia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Bilateral Lower Extremity Weakness	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Proteinuria	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Hyperglycemia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Pain, Left Axillary Area	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Pain, Back	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Constipation	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Left Hip Pain	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Gingival Infection	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Hypernatremia	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Rash-Acneiform	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.
Respiratory, thoracic and mediastinal disorders Yeast Infection	12.5% 1/8 • Number of events 1 • 26 months All noted adverse events were reported on the accrued patients. Hence the threshold is Zero.

Additional Information

George Simon, M.D.

Fox Chase Cancer Center (formerly at H. Lee Moffitt Cancer Center & Research Institute)

Phone: 215-728-2509

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place