BIO 300 Non-Small Cell Lung Cancer Study

Carcinoma, Non-Small-Cell Lung Clinical Trial

— NSCLC  

Official title:

A Phase I/II Clinical Study Evaluating the Safety and Effectiveness of BIO 300 Oral Suspension in Patients Receiving Chemoradiation Therapy for Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02567799
• Other study ID #: CL0101-01
• Secondary ID: HHSN261201200078
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2015
• Est. completion date: September 2020

Study information

• Verified date: January 2024
• Source: Humanetics Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: September 2020
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• BIO 300 Oral Suspension
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.
• Paclitaxel
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.
• Carboplatin
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.

Radiation:
• Radiotherapy
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.

Locations

Country	Name	City	State
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Henry Ford Hospital	Detroit	Michigan
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Zablocki VA Medical Center	Milwaukee	Wisconsin

Sponsors (6)

Lead Sponsor	Collaborator
Humanetics Corporation	Henry Ford Health System, Medical College of Wisconsin, Milwaukee VA Medical Center, National Cancer Institute (NCI), University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (1)

Simone CB 2nd, Serebrenik AA, Gore EM, Mohindra P, Brown SL, Wang D, Chetty IJ, Vujaskovic Z, Menon S, Thompson J, Fine G, Kaytor MD, Movsas B. Multicenter Phase 1b/2a Clinical Trial of Radioprotectant BIO 300 Oral Suspension for Patients With Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2024 Feb 1;118(2):404-414. doi: 10.1016/j.ijrobp.2023.08.048. Epub 2023 Aug 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 up to 6 weeks or maximum tolerated dose
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
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)	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
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.	Screening, visits 20, 37, 38, 39, 40, 41 & 42 (through visit 41 for surgical 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.	Screening, visits 20 and 3, 6, 11 & 13 months post radiation therapy
Secondary	DLCO as Measured by Pulmonary Function Test (PFT)		Screening and months 6 & 13 post radiation therapy completion
Secondary	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
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.	Screening and months 3, 6, & 13 post radiation therapy completion
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.	Screening and months 3, 6, & 13 post radiation therapy completion
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.	Screening, weeks 1, 2, 3, 4, 5, & 6 and months 3 & 6 post radiation therapy completion
Secondary	Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300		Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6
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).	Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6
Secondary	FVC as Measured by Pulmonary Function Test (PFT)		Screening and months 6 & 13 post radiation therapy completion
Secondary	FEV1 as Measured by Pulmonary Function Test (PFT)		Screening and months 6 & 13 post radiation therapy completion