Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Lung Neoplasms
Brief summary
The purpose of this study is to determine the safety and effectiveness of BIO 300 Oral Suspension when used in combination with standard dose radiation therapy and chemotherapy in patients with non-small cell lung cancer. Based on preclinical data the investigators hypothesize that BIO 300 Oral Suspension will reduce the incidence of radiation-induced pneumonitis and pulmonary fibrosis.
Detailed description
This is an open-label, single-arm, ascending dose Phase I/II study of BIO 300 Oral Suspension given in combination with paclitaxel/carboplatin and radiotherapy in subjects with stage II, III, or IV NSCLC who are candidates for combined chemoradiotherapy. A minimum of 6 subjects will be accrued sequentially at each dose level of BIO 300. BIO 300 will be administered daily for the entire course of concurrent chemoradiotherapy, a minimum of 6 weeks; in combination with standard paclitaxel / carboplatin chemotherapy and radiotherapy. The initial dose of BIO 300 will be administered on Day 1, Visit 2 in which safety data (adverse events, electrocardiograms (ECGs), results of safety laboratory determinations), pharmacokinetic (PK) and pharmacodynamic (PD) data will be collected. PK data will be collected from a minimum of six (6) study subjects from each cohort. PD data will be collected from all subjects in each study cohort. Day 1 of chemotherapy will be scheduled at the discretion of the investigator provided the subject has completed a minimum of 1 day of BIO 300 dosing. BIO 300 will be administered in combination with the chemotherapy components of the protocol (paclitaxel and carboplatin). During the first or second chemotherapy infusion, additional safety, PK and PD data will be collected. Day 1 of radiation therapy (RT) may be scheduled at the discretion of the investigator provided the subject has completed a minimum of 2 days of BIO 300 dosing. BIO 300 will continue to be administered daily; paclitaxel and carboplatin will be administered weekly and radiotherapy will be administered daily until a total dose of 60-70 Gy has been administered. During the period of combined BIO 300 and chemoradiotherapy (6-7 weeks), additional safety, PK and PD data will be collected weekly. An interim data analysis will be completed once the highest dose cohort concludes chemoradiation therapy, in an effort to determine the optimal biological dose. Following analysis, there will be an option to enroll up to an additional 12 subjects at the optimal biological dose. At the conclusion of the study, primary and secondary outcome measures will be evaluated. Data will be analyzed from all cohorts to determine the oncologic response, safety of BIO 300, and a recommended BIO 300 dose.
Interventions
Cohort 1: BIO 300 500 mg Cohort 2: BIO 300 1,000 mg Cohort 3: BIO 300 1,500 mg Cohort 4: BIO 300 Optimal dose (TBD) BIO 300 dose will be given daily, 7 days/week (Week 1, day 1 through week 6) The 2nd and 3rd dosing cohort (1,000 and 1,500 mg/day) will begin following the accrual of a minimum of 6 subjects at the previous dose level, dose escalation to the next BIO 300 dose level will be allowed to occur when a cohort has completed concurrent chemoradiotherapy with fewer than 33% Dose Limiting Toxicities (DLTs) attributed to BIO 300 Oral Suspension.
DRUGPaclitaxel
During the Concurrent Therapy period, paclitaxel 45 mg/m2 will be administered by intravenous drip weekly during weeks 1-6. During the Consolidation Therapy period, paclitaxel 200 mg/m2 will be administered by intravenous drip two times, 21 days apart.
DRUGCarboplatin
During the Concurrent Therapy period, area under the curve (AUC) = 2mg\* min/mL will be administered by intravenous drip weekly during weeks 1-6. During the Consolidation Therapy period, carboplatin AUC = 6mg\*min/mL will be administered by intravenous drip two times, 21 days apart.
RADIATIONRadiotherapy
Radiation treatment will be scheduled at the discretion of the investigator provided the subject has completed a minimum of 2 days of BIO 300 dosing. Subjects will receive radiation therapy 5 days per week, once daily fractions, 1.8-2.0 Gy per fraction, for 6-7 weeks.
Sponsors
National Cancer Institute (NCI)
Henry Ford Health System
Medical College of Wisconsin
University of Maryland, Baltimore
Milwaukee VA Medical Center
Humanetics Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histological or cytological confirmation of NSCLC 2. Stage II, III, or IV NSCLC for whom radiation therapy of 60 Gy and concurrent weekly paclitaxel/carboplatin is recommended 3. Up to three small (≤ 3 cm each) lung oligometastases will be allowed and/or one oligometastasis at any other site in the body 4. Eastern Cooperative Oncology Group Performance Scale (ECOG PS) of 0 or 1 5. Forced expiratory volume at one second (FEV1): best value obtained pre- or post-bronchodilator must be ≥ 1.0 liters/second or \> 50% predicted value 6. Adequate bone marrow reserve 7. Adequate hepatic reserve 8. Adequate renal function 9. Female subjects of childbearing potential must have a negative pregnancy test 10. Female subjects of childbearing potential and male subjects with female sexual partners of childbearing potential must agree to use an effective method of contraception 11. Ability to read and provide written informed consent
Exclusion criteria
1. Weight loss greater than 10% in prior 4 weeks 2. Prior malignancy in which they received any thoracic radiotherapy unless the treating physician considers it unlikely to impact the clinical outcome of the patient 3. Patients with concurrent invasive malignancy other than non-melanoma skin cancer or cervical intraepithelial neoplasia unless the treating physician considers it unlikely to impact the clinical outcome of the patient 4. An active infection or with a fever ≥ 38.5°C 5. Poorly controlled intercurrent illnesses 6. Patients with a prior thoracotomy within 1 week of study registration 7. Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration 8. Patients with any of the following are not eligible: * Previous history of Corrected QT Interval (QTc ) prolongation resulting from medication that required discontinuation of that medication * Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age; * Presence of left bundle branch block (LBBB); * QTc with Fridericia's correction that is unmeasurable, or ≥ 480 msec on screening ECG. The average QTc from the screening ECG (completed in triplicate) must be \< 480 msec in order for the patient to be eligible for the study; * Subjects taking any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes are not eligible if QTc ≥ 460 msec. 9. Patients must not have had a clinically significant cardiac event within 6 months before entry; or the presence of any other uncontrolled cardiovascular conditions that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. 10. Patients with a history of arrhythmia or asymptomatic sustained ventricular tachycardia are not eligible. Patients with atrial fibrillation with well-controlled ventricular rate on medication, are eligible. 11. Psychiatric conditions, social situations or substance abuse that precludes the ability of the subject to cooperate with the requirements of the trial and protocol therapy 12. Grade 2 or higher peripheral neuropathy 13. Known history of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS), hepatitis B or C. 14. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception 15. Women who are breastfeeding are not eligible for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Day 1 up to 6 weeks or maximum tolerated dose | Adverse events of CTCAE v4.0 grade 3 or higher that were possibly, probably or definitely related to BIO 300 Oral Suspension and have occurred before or during concurrent chemoradiotherapy were considered dose limiting toxicities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300 | Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose | — |
| Number of Participants With Adverse Events Throughout the Study | Day 1 up to month 13 post radiation or 12 months post chemotherapy consolidation for surgical participants. | — |
| Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy | Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose | — |
| Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy | Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose | — |
| Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose | — |
| Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose | — |
| Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300 | Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose | — |
| Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300 | Week1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose | — |
| Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Screening, once weekly during weeks 1-6 of concurrent chemoradiotherapy prior to BIO 300, paclitaxel, and carboplatin dose, and once at the end of consolidation, 3 months and 6 months after the completion of RT | Measuring change from baseline (screening visit) of TGF-beta isoform 1 (TGFB1) |
| Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Screening, visits 20, 37, 38, 39, 40, 41 & 42 (through visit 41 for surgical participants) | Best Response Rate reported per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by chest CT imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
| Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300 | Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose | — |
| DLCO as Measured by Pulmonary Function Test (PFT) | Screening and months 6 & 13 post radiation therapy completion | — |
| Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT) | Screening, visits 20 & 37 and 9 & 13 months post radiation therapy for non-surgical participants; screening only for surgical participants | — |
| Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | Screening and months 3, 6, & 13 post radiation therapy completion | The Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) questionnaire is a 36-item self-reporting instrument that measures quality of life specific to patients with cancer. Items are rated on a 5 item (point) Likert Scale, from 0 (not at all) to 4 (very much). Total scores range from 0 to 136 and higher scores indicate better quality of life. The FACT-L TOI questionnaire was scored according to FACT-L Scoring Guidelines Version 4. |
| Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | Screening and months 3, 6, & 13 post radiation therapy completion | The UCSD-SOBQ is a 24-item patient self-reported questionnaire where items are scored on a 6-point scale (0, not at all to 5, maximal or unable to-do because of breathlessness). Total scores range from 0 to 120 and lower scores indicate better quality of life. |
| Extent of Esophagitis by Patient Reported Swallowing Diary | Screening, weeks 1, 2, 3, 4, 5, & 6 and months 3 & 6 post radiation therapy completion | The assessment will provide a score (the swallowing questionnaire) from 0 to 5; 1 no problems swallowing; 2 mild soreness only; 3 some difficulty swallowing solids; 4 cannot swallow solids; and 5 cannot swallow liquids. |
| Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6 | — |
| Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6 | Serum trough levels of paclitaxel and carboplatin were measured. Carboplatin trough levels were below the limit of quantification at all timepoints and are therefore reported as NA (Not Available). |
| FVC as Measured by Pulmonary Function Test (PFT) | Screening and months 6 & 13 post radiation therapy completion | — |
| FEV1 as Measured by Pulmonary Function Test (PFT) | Screening and months 6 & 13 post radiation therapy completion | — |
| Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | Screening, visits 20 and 3, 6, 11 & 13 months post radiation therapy | Tumor diameter was measured in centimeters. Mean change in tumor diameter from the baseline measurement at screening is reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BIO 300 Oral Suspension (500 mg/Day) BIO 300 Oral Suspension (500 mg/day) was given daily, 7 days/week (Week 1, day 1 through the end of concurrent chemoradiotherapy, Weeks 6-7). | 7 |
| BIO 300 Oral Suspension (1000 mg/Day) BIO 300 Oral Suspension (1000 mg/day) was given daily, 7 days/week (Week 1, day 1 through the end of concurrent chemoradiotherapy, Weeks 6-7). | 7 |
| BIO 300 Oral Suspension (1500 mg/Day) BIO 300 Oral Suspension (1500 mg/day) was given daily, 7 days/week (Week 1, day 1 through the end of concurrent chemoradiotherapy, Weeks 6-7). | 7 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Concurrent Chemoradiotherapy | Adverse Event | 0 | 1 | 0 |
| Concurrent Chemoradiotherapy | Death | 1 | 0 | 0 |
| Concurrent Chemoradiotherapy | Progressive Disease | 0 | 2 | 1 |
| Follow-up | Death | 1 | 0 | 1 |
| Follow-up | Progressive Disease | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | BIO 300 Oral Suspension (500 mg/Day) | BIO 300 Oral Suspension (1000 mg/Day) | BIO 300 Oral Suspension (1500 mg/Day) | Total |
|---|---|---|---|---|
| Age, Continuous | 78 years | 69 years | 57 years | 69 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 7 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Initial Tumor Stage Stage II | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Initial Tumor Stage Stage III | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Initial Tumor Stage Stage IV | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Primary Tumor Location Left Lower Lobe | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Primary Tumor Location Left Upper Lobe | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Primary Tumor Location Right Lower Lobe | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Primary Tumor Location Right Middle Lobe | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Primary Tumor Location Right Upper Lobe | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 7 Participants | 6 Participants | 19 Participants |
| Region of Enrollment United States | 7 participants | 7 participants | 7 participants | 21 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 6 Participants | 10 Participants |
| Tumor Histology Adenocarcinoma | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Tumor Histology Squamous | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 7 | 0 / 7 | 1 / 7 |
| other Total, other adverse events | 7 / 7 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 3 / 7 | 1 / 7 | 2 / 7 |
Outcome results
Primary
Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity
Adverse events of CTCAE v4.0 grade 3 or higher that were possibly, probably or definitely related to BIO 300 Oral Suspension and have occurred before or during concurrent chemoradiotherapy were considered dose limiting toxicities.
Time frame: Day 1 up to 6 weeks or maximum tolerated dose
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Number of Participants Experiencing DLTs | 0 Participants |
| BIO 300 Oral Suspension (500 mg/Day) | Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Number of Participants That Did Not Experience a DLT | 6 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Number of Participants Experiencing DLTs | 0 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Number of Participants That Did Not Experience a DLT | 7 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Number of Participants Experiencing DLTs | 0 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Number of Participants With BIO 300 Oral Suspension-related Dose Limiting Toxicity | Number of Participants That Did Not Experience a DLT | 7 Participants |
Secondary
Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan
Tumor diameter was measured in centimeters. Mean change in tumor diameter from the baseline measurement at screening is reported.
Time frame: Screening, visits 20 and 3, 6, 11 & 13 months post radiation therapy
Population: Number of participants vary based on the number of subjects that completed a CT scan each timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | Visit 20 | -1.30 Mean Change from Baseline (cm) | Standard Deviation 1.2 |
| BIO 300 Oral Suspension (500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 3 Months Post-RT | -2.83 Mean Change from Baseline (cm) | Standard Deviation 1.35 |
| BIO 300 Oral Suspension (500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 6 Months Post-RT | -2.43 Mean Change from Baseline (cm) | Standard Deviation 0.99 |
| BIO 300 Oral Suspension (500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 9 Months Post-RT | -2.58 Mean Change from Baseline (cm) | Standard Deviation 0.87 |
| BIO 300 Oral Suspension (500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 11 Months Post-RT | -2.55 Mean Change from Baseline (cm) | Standard Deviation 0.95 |
| BIO 300 Oral Suspension (500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 13 Months Post-RT | -2.33 Mean Change from Baseline (cm) | Standard Deviation 1.31 |
| BIO 300 Oral Suspension (1000 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 13 Months Post-RT | -3.13 Mean Change from Baseline (cm) | Standard Deviation 1.27 |
| BIO 300 Oral Suspension (1000 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | Visit 20 | 0.04 Mean Change from Baseline (cm) | Standard Deviation 3.24 |
| BIO 300 Oral Suspension (1000 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 9 Months Post-RT | -3.25 Mean Change from Baseline (cm) | Standard Deviation 0.49 |
| BIO 300 Oral Suspension (1000 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 11 Months Post-RT | -3.10 Mean Change from Baseline (cm) | Standard Deviation 0.56 |
| BIO 300 Oral Suspension (1000 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 3 Months Post-RT | -2.29 Mean Change from Baseline (cm) | Standard Deviation 0.82 |
| BIO 300 Oral Suspension (1000 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 6 Months Post-RT | -3.23 Mean Change from Baseline (cm) | Standard Deviation 1.02 |
| BIO 300 Oral Suspension (1500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 3 Months Post-RT | -3.54 Mean Change from Baseline (cm) | Standard Deviation 1.86 |
| BIO 300 Oral Suspension (1500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 6 Months Post-RT | -3.42 Mean Change from Baseline (cm) | Standard Deviation 2.08 |
| BIO 300 Oral Suspension (1500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 13 Months Post-RT | -3.05 Mean Change from Baseline (cm) | Standard Deviation 5.02 |
| BIO 300 Oral Suspension (1500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 9 Months Post-RT | -5.0 Mean Change from Baseline (cm) | Standard Deviation 1.75 |
| BIO 300 Oral Suspension (1500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | Visit 20 | -1.15 Mean Change from Baseline (cm) | Standard Deviation 1.63 |
| BIO 300 Oral Suspension (1500 mg/Day) | Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan | 11 Months Post-RT | -5.9 Mean Change from Baseline (cm) | Standard Deviation 0 |
Secondary
DLCO as Measured by Pulmonary Function Test (PFT)
Time frame: Screening and months 6 & 13 post radiation therapy completion
Population: Number of participants varies based on the number of study subjects that received each assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 10.83 mL/mmHg/Min | Standard Deviation 4.31 |
| BIO 300 Oral Suspension (500 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | Baseline | 12.12 mL/mmHg/Min | Standard Deviation 3.8 |
| BIO 300 Oral Suspension (500 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 11.65 mL/mmHg/Min | Standard Deviation 4.61 |
| BIO 300 Oral Suspension (1000 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 10.46 mL/mmHg/Min | Standard Deviation 4.27 |
| BIO 300 Oral Suspension (1000 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | Baseline | 14.96 mL/mmHg/Min | Standard Deviation 3.28 |
| BIO 300 Oral Suspension (1000 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 9.48 mL/mmHg/Min | Standard Deviation 1.92 |
| BIO 300 Oral Suspension (1500 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | Baseline | 16.15 mL/mmHg/Min | Standard Deviation 6.6 |
| BIO 300 Oral Suspension (1500 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 18.95 mL/mmHg/Min | Standard Deviation 1.09 |
| BIO 300 Oral Suspension (1500 mg/Day) | DLCO as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 11.28 mL/mmHg/Min | Standard Deviation 5.82 |
Secondary
Extent of Esophagitis by Patient Reported Swallowing Diary
The assessment will provide a score (the swallowing questionnaire) from 0 to 5; 1 no problems swallowing; 2 mild soreness only; 3 some difficulty swallowing solids; 4 cannot swallow solids; and 5 cannot swallow liquids.
Time frame: Screening, weeks 1, 2, 3, 4, 5, & 6 and months 3 & 6 post radiation therapy completion
Population: Number of participants at each time point vary based on the number of study participants that completed the assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | 3 months post-RT | 1.0 Swallowing Diary Score | Standard Deviation 0 |
| BIO 300 Oral Suspension (500 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | Weeks 1-6 Average | 1.2 Swallowing Diary Score | Standard Deviation 0.36 |
| BIO 300 Oral Suspension (500 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | 6 months post-RT | 1.33 Swallowing Diary Score | Standard Deviation 0.58 |
| BIO 300 Oral Suspension (1000 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | 3 months post-RT | 1.0 Swallowing Diary Score | Standard Deviation 0 |
| BIO 300 Oral Suspension (1000 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | Weeks 1-6 Average | 1.54 Swallowing Diary Score | Standard Deviation 0.41 |
| BIO 300 Oral Suspension (1000 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | 6 months post-RT | 1.0 Swallowing Diary Score | Standard Deviation 0 |
| BIO 300 Oral Suspension (1500 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | Weeks 1-6 Average | 1.64 Swallowing Diary Score | Standard Deviation 0.87 |
| BIO 300 Oral Suspension (1500 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | 6 months post-RT | 1.6 Swallowing Diary Score | Standard Deviation 0.55 |
| BIO 300 Oral Suspension (1500 mg/Day) | Extent of Esophagitis by Patient Reported Swallowing Diary | 3 months post-RT | 1.6 Swallowing Diary Score | Standard Deviation 0.89 |
Secondary
FEV1 as Measured by Pulmonary Function Test (PFT)
Time frame: Screening and months 6 & 13 post radiation therapy completion
Population: Number of participants varies based on the number of study subjects that received each assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 1.61 Liters | Standard Deviation 0.55 |
| BIO 300 Oral Suspension (500 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 1.71 Liters | Standard Deviation 0.53 |
| BIO 300 Oral Suspension (500 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | Baseline | 1.69 Liters | Standard Deviation 0.38 |
| BIO 300 Oral Suspension (1000 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 1.29 Liters | Standard Deviation 0.13 |
| BIO 300 Oral Suspension (1000 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | Baseline | 1.91 Liters | Standard Deviation 0.59 |
| BIO 300 Oral Suspension (1000 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 1.26 Liters | Standard Deviation 0.06 |
| BIO 300 Oral Suspension (1500 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | Baseline | 2.39 Liters | Standard Deviation 0.83 |
| BIO 300 Oral Suspension (1500 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 2.39 Liters | Standard Deviation 0.27 |
| BIO 300 Oral Suspension (1500 mg/Day) | FEV1 as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 2.03 Liters | Standard Deviation 0.6 |
Secondary
FVC as Measured by Pulmonary Function Test (PFT)
Time frame: Screening and months 6 & 13 post radiation therapy completion
Population: Number of participants varies based on the number of study subjects that received each assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 2.32 Liters | Standard Deviation 0.65 |
| BIO 300 Oral Suspension (500 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | Baseline | 2.46 Liters | Standard Deviation 0.46 |
| BIO 300 Oral Suspension (500 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 2.32 Liters | Standard Deviation 0.67 |
| BIO 300 Oral Suspension (1000 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 2.1 Liters | Standard Deviation 0.6 |
| BIO 300 Oral Suspension (1000 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | Baseline | 2.79 Liters | Standard Deviation 0.56 |
| BIO 300 Oral Suspension (1000 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 2.19 Liters | Standard Deviation 0.44 |
| BIO 300 Oral Suspension (1500 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | Baseline | 3.51 Liters | Standard Deviation 0.85 |
| BIO 300 Oral Suspension (1500 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | 13 months post-RT | 3.28 Liters | Standard Deviation 0.27 |
| BIO 300 Oral Suspension (1500 mg/Day) | FVC as Measured by Pulmonary Function Test (PFT) | 6 months post-RT | 2.93 Liters | Standard Deviation 0.74 |
Secondary
Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy
Time frame: Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy | 857 ng*hr/mL | Standard Deviation 341 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy | 1493 ng*hr/mL | Standard Deviation 1123 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy | 1570 ng*hr/mL | Standard Deviation 883 |
Secondary
Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin
Time frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | 1371 ng*hr/mL | Standard Deviation 1174 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | 1578 ng*hr/mL | Standard Deviation 726 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | 1821 ng*hr/mL | Standard Deviation 964 |
Secondary
Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300
Time frame: Week1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300 | 30810.04 ng*hr/mL | Standard Deviation 5729.8 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300 | 41785.18 ng*hr/mL | Standard Deviation 11133.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300 | 41753.3 ng*hr/mL | Standard Deviation 14462.78 |
Secondary
Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300
Time frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300 | 1236.51 ng*hr/mL | Standard Deviation 680.63 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300 | 1796.1 ng*hr/mL | Standard Deviation 409.49 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300 | 755.27 ng*hr/mL | Standard Deviation 306.45 |
Secondary
Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy
Time frame: Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy | 174 ng/mL | Standard Deviation 74 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy | 302 ng/mL | Standard Deviation 194 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy | 388 ng/mL | Standard Deviation 264 |
Secondary
Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin
Time frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | 155 ng/mL | Standard Deviation 30 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | 427 ng/mL | Standard Deviation 339 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin | 414 ng/mL | Standard Deviation 257 |
Secondary
Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300
Time frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300 | 7594 ng/mL | Standard Deviation 1946.03 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300 | 9938.33 ng/mL | Standard Deviation 3452.58 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300 | 12883.33 ng/mL | Standard Deviation 7446.87 |
Secondary
Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300
Time frame: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose
Population: Only participants that had blood draws for pharmacokinetics were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300 | 665.5 ng/mL | Standard Deviation 588.06 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300 | 1026.5 ng/mL | Standard Deviation 260.36 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300 | 307.6 ng/mL | Standard Deviation 288.2 |
Secondary
Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300
Time frame: Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6
Population: Number of participants analyzed at each time point varies based on the number of subjects available for pharmacokinetic blood draw
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 1 | 44.2 ng/mL | Standard Deviation 90 |
| BIO 300 Oral Suspension (500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 2 | 32.6 ng/mL | Standard Deviation 44.2 |
| BIO 300 Oral Suspension (500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 3 | 5.1 ng/mL | Standard Deviation 4.5 |
| BIO 300 Oral Suspension (500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 4 | 8.3 ng/mL | Standard Deviation 13.9 |
| BIO 300 Oral Suspension (500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 5 | 40.7 ng/mL | Standard Deviation 36.2 |
| BIO 300 Oral Suspension (500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 6 | 12.4 ng/mL | Standard Deviation 15.7 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 3 | 5.56 ng/mL | Standard Deviation 8 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 4 | 3.82 ng/mL | Standard Deviation 6 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 6 | 24.0 ng/mL | Standard Deviation 32.5 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 5 | 6.71 ng/mL | Standard Deviation 11.9 |
| BIO 300 Oral Suspension (1000 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 2 | 5.84 ng/mL | Standard Deviation 8.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 5 | 23.54 ng/mL | Standard Deviation 38 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 1 | 16.02 ng/mL | Standard Deviation 23.7 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 3 | 14.12 ng/mL | Standard Deviation 18.6 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 6 | 24.54 ng/mL | Standard Deviation 23.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 2 | 9.96 ng/mL | Standard Deviation 13.9 |
| BIO 300 Oral Suspension (1500 mg/Day) | Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300 | Week 4 | 22.66 ng/mL | Standard Deviation 44.7 |
Secondary
Number of Participants With Adverse Events Throughout the Study
Time frame: Day 1 up to month 13 post radiation or 12 months post chemotherapy consolidation for surgical participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Number of Participants With Adverse Events Throughout the Study | 7 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Number of Participants With Adverse Events Throughout the Study | 7 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Number of Participants With Adverse Events Throughout the Study | 7 Participants |
Secondary
Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT)
Time frame: Screening, visits 20 & 37 and 9 & 13 months post radiation therapy for non-surgical participants; screening only for surgical participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT) | 0 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT) | 0 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT) | 0 Participants |
Secondary
Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1)
Measuring change from baseline (screening visit) of TGF-beta isoform 1 (TGFB1)
Time frame: Screening, once weekly during weeks 1-6 of concurrent chemoradiotherapy prior to BIO 300, paclitaxel, and carboplatin dose, and once at the end of consolidation, 3 months and 6 months after the completion of RT
Population: Analysis population only includes subjects that had a baseline measurement during the screening visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | 6 months post-RT | 106.5 Percent change from baseline | Standard Deviation 57.4 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 6 | 142.8 Percent change from baseline | Standard Deviation 133.9 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 4 | 90.6 Percent change from baseline | Standard Deviation 66 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | 3 months post-RT | 205.7 Percent change from baseline | Standard Deviation 161.2 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 5 | 88.5 Percent change from baseline | Standard Deviation 86.8 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 2 | 130.3 Percent change from baseline | Standard Deviation 79.9 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 1 | 141.8 Percent change from baseline | Standard Deviation 64.1 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | After consolidation therapy | 68.7 Percent change from baseline | Standard Deviation 44.2 |
| BIO 300 Oral Suspension (500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 3 | 108.6 Percent change from baseline | Standard Deviation 79 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | 6 months post-RT | 130.5 Percent change from baseline | Standard Deviation 93.5 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 1 | 96.7 Percent change from baseline | Standard Deviation 5.1 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 2 | 127.5 Percent change from baseline | Standard Deviation 77.9 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 3 | 60.1 Percent change from baseline | Standard Deviation 40.1 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 4 | 69.0 Percent change from baseline | Standard Deviation 43.8 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 5 | 61.7 Percent change from baseline | Standard Deviation 44.3 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 6 | 69.3 Percent change from baseline | Standard Deviation 43.9 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | After consolidation therapy | 74.3 Percent change from baseline | Standard Deviation 78.5 |
| BIO 300 Oral Suspension (1000 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | 3 months post-RT | 144.9 Percent change from baseline | Standard Deviation 96.4 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | 6 months post-RT | 61.2 Percent change from baseline | Standard Deviation 36.6 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 6 | 33.4 Percent change from baseline | Standard Deviation 33.5 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 2 | 96.7 Percent change from baseline | Standard Deviation 38.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | 3 months post-RT | 83.1 Percent change from baseline | Standard Deviation 18.7 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | After consolidation therapy | 60.8 Percent change from baseline | Standard Deviation 28.4 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 4 | 55.8 Percent change from baseline | Standard Deviation 19.9 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 1 | 117.3 Percent change from baseline | Standard Deviation 48.5 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 5 | 51.2 Percent change from baseline | Standard Deviation 12.1 |
| BIO 300 Oral Suspension (1500 mg/Day) | Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1) | Week 3 | 74.4 Percent change from baseline | Standard Deviation 25.9 |
Secondary
Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire.
The Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) questionnaire is a 36-item self-reporting instrument that measures quality of life specific to patients with cancer. Items are rated on a 5 item (point) Likert Scale, from 0 (not at all) to 4 (very much). Total scores range from 0 to 136 and higher scores indicate better quality of life. The FACT-L TOI questionnaire was scored according to FACT-L Scoring Guidelines Version 4.
Time frame: Screening and months 3, 6, & 13 post radiation therapy completion
Population: Number of participants at each time point vary based on the number of study participants that completed the assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | Screening | 66.6 FACT-L Total Score | Standard Deviation 10.8 |
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 3 months post-RT | 54.5 FACT-L Total Score | Standard Deviation 16.4 |
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 6 months post-RT | 55.4 FACT-L Total Score | Standard Deviation 15.5 |
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 13 months post-RT | 50.8 FACT-L Total Score | Standard Deviation 22.4 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 13 months post-RT | 61.5 FACT-L Total Score | Standard Deviation 18.1 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | Screening | 53.8 FACT-L Total Score | Standard Deviation 21.5 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 6 months post-RT | 49.7 FACT-L Total Score | Standard Deviation 13.5 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 3 months post-RT | 63.0 FACT-L Total Score | Standard Deviation 6.7 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 13 months post-RT | 55.0 FACT-L Total Score | Standard Deviation 13.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 3 months post-RT | 55.6 FACT-L Total Score | Standard Deviation 13.3 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | 6 months post-RT | 51.4 FACT-L Total Score | Standard Deviation 15 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Lung Scale Trial Outcome Index (FACT-L TOI) Patient Reported Outcome Questionnaire. | Screening | 53.9 FACT-L Total Score | Standard Deviation 13.2 |
Secondary
Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire.
The UCSD-SOBQ is a 24-item patient self-reported questionnaire where items are scored on a 6-point scale (0, not at all to 5, maximal or unable to-do because of breathlessness). Total scores range from 0 to 120 and lower scores indicate better quality of life.
Time frame: Screening and months 3, 6, & 13 post radiation therapy completion
Population: Number of participants at each time point vary based on the number of study participants that completed the assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | Screening | 19.4 UCSD-SOBQ Total Score | Standard Deviation 17.4 |
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 3 months post-RT | 37.0 UCSD-SOBQ Total Score | Standard Deviation 33.5 |
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 6 months post-RT | 46.8 UCSD-SOBQ Total Score | Standard Deviation 31.1 |
| BIO 300 Oral Suspension (500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 13 months post-RT | 64.0 UCSD-SOBQ Total Score | Standard Deviation 43.6 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 13 months post-RT | 39.8 UCSD-SOBQ Total Score | Standard Deviation 23.4 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | Screening | 29.9 UCSD-SOBQ Total Score | Standard Deviation 32.3 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 6 months post-RT | 54.7 UCSD-SOBQ Total Score | Standard Deviation 26.6 |
| BIO 300 Oral Suspension (1000 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 3 months post-RT | 38.0 UCSD-SOBQ Total Score | Standard Deviation 13.9 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 13 months post-RT | 23.2 UCSD-SOBQ Total Score | Standard Deviation 18 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 3 months post-RT | 23.0 UCSD-SOBQ Total Score | Standard Deviation 20.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | 6 months post-RT | 24.8 UCSD-SOBQ Total Score | Standard Deviation 20.8 |
| BIO 300 Oral Suspension (1500 mg/Day) | Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire. | Screening | 13.9 UCSD-SOBQ Total Score | Standard Deviation 11.9 |
Secondary
Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria
Best Response Rate reported per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by chest CT imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), At least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Screening, visits 20, 37, 38, 39, 40, 41 & 42 (through visit 41 for surgical participants)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Complete Response | 0 Participants |
| BIO 300 Oral Suspension (500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Partial Response | 5 Participants |
| BIO 300 Oral Suspension (500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Stable Disease | 1 Participants |
| BIO 300 Oral Suspension (500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Progressive Disease | 0 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Progressive Disease | 0 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Complete Response | 2 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Stable Disease | 3 Participants |
| BIO 300 Oral Suspension (1000 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Partial Response | 2 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Progressive Disease | 0 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Partial Response | 2 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Stable Disease | 3 Participants |
| BIO 300 Oral Suspension (1500 mg/Day) | Rate of Progressive Disease Evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) Criteria | Complete Response | 2 Participants |
Secondary
Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin
Serum trough levels of paclitaxel and carboplatin were measured. Carboplatin trough levels were below the limit of quantification at all timepoints and are therefore reported as NA (Not Available).
Time frame: Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6
Population: Number of participants at each time point varies based on the number of participants with blood sample available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BIO 300 Oral Suspension (500 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 2 | 1.09 ng/mL | Standard Deviation 0.19 |
| BIO 300 Oral Suspension (500 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 4 | 1.83 ng/mL | Standard Deviation 0.81 |
| BIO 300 Oral Suspension (500 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 1 | 1.04 ng/mL | Standard Deviation 0.08 |
| BIO 300 Oral Suspension (500 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 5 | 1.90 ng/mL | Standard Deviation 0.96 |
| BIO 300 Oral Suspension (500 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 3 | 1.53 ng/mL | Standard Deviation 0.93 |
| BIO 300 Oral Suspension (500 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 6 | 1.92 ng/mL | Standard Deviation 1.19 |
| BIO 300 Oral Suspension (1000 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 3 | NA ng/mL | — |
| BIO 300 Oral Suspension (1000 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 1 | NA ng/mL | — |
| BIO 300 Oral Suspension (1000 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 2 | NA ng/mL | — |
| BIO 300 Oral Suspension (1000 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 6 | NA ng/mL | — |
| BIO 300 Oral Suspension (1000 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 4 | NA ng/mL | — |
| BIO 300 Oral Suspension (1000 mg/Day) | Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin | Week 5 | NA ng/mL | — |