Trial Outcomes & Findings for Avastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer (NCT NCT00271505)

Last Updated: 2020-05-11

Results Overview

Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naı¨ve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standards, front-line, platinum-based doublets have not been extensively explored.We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naı¨ve patients with advanced, on squamous NSCLC.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

Baseline up to 12 months or disease progression/death

Results posted on

2020-05-11

Participant Flow

The trial was interrupted before the planned 50 patients were enrolled because of slow accrual after bevacizumab became commercially available in the United States for NSCLC treatment.

Participant milestones

Participant milestones
Measure	Carboplatin (AUC 6), Docetaxel (75 mg/m2), and Bevacizumab ( Patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Six cycles of chemotherapy plus bevacizumab were planned. Patients who demonstrated stable disease (SD), partial response (PR), or complete response (CR) to treatment continued on single-agent bevacizumab 15 mg/kg every 21 days until disease progression or intolerable toxicity. Patients who discontinued chemotherapy before 6 cycles of treatment were also allowed to continue on single-agent bevacizumab in the absence of progressive disease (PD).
Overall Study STARTED	43
Overall Study COMPLETED	38
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Carboplatin (AUC 6), Docetaxel (75 mg/m2), and Bevacizumab ( Patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Six cycles of chemotherapy plus bevacizumab were planned. Patients who demonstrated stable disease (SD), partial response (PR), or complete response (CR) to treatment continued on single-agent bevacizumab 15 mg/kg every 21 days until disease progression or intolerable toxicity. Patients who discontinued chemotherapy before 6 cycles of treatment were also allowed to continue on single-agent bevacizumab in the absence of progressive disease (PD).
Overall Study Screen Failure	3
Overall Study Adverse Event	1
Overall Study Death	1

Baseline Characteristics

Avastin/Docetaxel/Carboplatin in Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Carboplatin, Docetaxel, and Bevacizumab n=40 Participants Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression-free survival. Six cycles of chemotherapy plus bevacizumab were planned. Patients who demonstrated stable disease (SD), partial response (PR), or complete response (CR) to treatment continued on single-agent bevacizumab 15 mg/kg every 21 days until disease progression or intolerable toxicity. Patients who discontinued chemotherapy before 6 cycles of treatment were also allowed to continue on single-agent bevacizumab in the absence of progressive disease (PD).
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to 12 months or disease progression/death

Outcome measures

Outcome measures
Measure	Carboplatin, Docetaxel, and Bevacizumab n=38 Participants Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days
Time to Progression-Free Survival (PFS)	7.9 months Interval 6.0 to 11.1

SECONDARY outcome

Timeframe: Baseline start of treatment to death, assessed up to 6 years

Secondary endpoints of the study included the assessment of overall survival, disease control rate (CR þPR þ SD, defined by RECIST16), and evaluation of the safety profile of this triple-agent regimen. All patients who received at least 1 dose of the study drug were analyzed for efficacy and toxicity endpoints.

Outcome measures

Outcome measures
Measure	Carboplatin, Docetaxel, and Bevacizumab n=40 Participants Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days
Overall Survival (OS)- 5 Years	16.5 months Interval 13.6 to 31.2

SECONDARY outcome

Timeframe: Baseline start of treatment to death, assessed up to 6 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1 .0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)= CR+ PR.

Outcome measures

Outcome measures
Measure	Carboplatin, Docetaxel, and Bevacizumab n=40 Participants Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days
Disease Control Rate	95 percentage of participants Interval 88.0 to 100.0

Adverse Events

Carboplatin,Docetaxel, and Bevacizumab

Serious events: 13 serious events

Other events: 25 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Carboplatin,Docetaxel, and Bevacizumab n=40 participants at risk Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days
Blood and lymphatic system disorders Hemoptysis	2.5% 1/40 • through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders Pulmonary Hemmorhage	2.5% 1/40 • through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders embolism	2.5% 1/40 • through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders Pleural Effusion	2.5% 1/40 • through study completion, an average of 1 year
Blood and lymphatic system disorders Fatigue	2.5% 1/40 • through study completion, an average of 1 year
Gastrointestinal disorders Perforation Duodenum G4	2.5% 1/40 • through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders Dyspnea	2.5% 1/40 • through study completion, an average of 1 year
Blood and lymphatic system disorders Deep Vein Thrombosis	2.5% 1/40 • through study completion, an average of 1 year
Gastrointestinal disorders Rt Ing Hernia	2.5% 1/40 • through study completion, an average of 1 year
Blood and lymphatic system disorders Fatigue & Infection G3	2.5% 1/40 • through study completion, an average of 1 year
Blood and lymphatic system disorders Mild Anemia of Chronic Disease and Fatigue	2.5% 1/40 • through study completion, an average of 1 year
General disorders Sudden Death	2.5% 1/40 • through study completion, an average of 1 year
Respiratory, thoracic and mediastinal disorders Death	2.5% 1/40 • through study completion, an average of 1 year

Other adverse events

Other adverse events
Measure	Carboplatin,Docetaxel, and Bevacizumab n=40 participants at risk Up to 6 cycles of carboplatin (AUC 6), Tocetaxel (75 mg/m2), and Bevacizumab (15 mg/kg) on Day 1 every 21 days
Blood and lymphatic system disorders Anemia	25.0% 10/40 • through study completion, an average of 1 year
Skin and subcutaneous tissue disorders Alopecia	62.5% 25/40 • through study completion, an average of 1 year
Gastrointestinal disorders Anorexia	25.0% 10/40 • through study completion, an average of 1 year
Gastrointestinal disorders Constipation	37.5% 15/40 • through study completion, an average of 1 year
Gastrointestinal disorders Diarrhea	27.5% 11/40 • through study completion, an average of 1 year
General disorders Fatigue	52.5% 21/40 • through study completion, an average of 1 year
Skin and subcutaneous tissue disorders Nail Change	32.5% 13/40 • through study completion, an average of 1 year
Endocrine disorders Hyperglycemia	52.5% 21/40 • through study completion, an average of 1 year
Metabolism and nutrition disorders Hypomagnesemia	50.0% 20/40 • through study completion, an average of 1 year
Gastrointestinal disorders Nausea	37.5% 15/40 • through study completion, an average of 1 year
Skin and subcutaneous tissue disorders Stomatitis	22.5% 9/40 • through study completion, an average of 1 year

Additional Information

Dr. John V Heymach, PHD/ Chair, Thoracic-Head & Neck Med Onc

UT MD Anderson Cancer Center

Phone: 713-792-6363

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place