Continuous Dosing of BAY73-4506 in Patients With Advanced Malignancies

NCT01117623 | Completed Phase 1 Results

• 1 other identifier: 11651
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 5

Brief Summary

Continuous dosing of BAY73-4506 in patients with advanced cancer

Conditions

Neoplasm

Keywords

Oncology patients with advanced disease; BAY73-4506

Outcome Measures

Primary Outcomes (5)

• Maximum Tolerated Dose (MTD)

  The MTD was defined as the highest dose level, which could be given to 6 participants such that no more than 1 participant (less than 33%) experienced a dose-limiting toxicity (DLT).

  Within first 4 weeks of treatment

• Maximum Observed Plasma Concentration After Single Dose Administration (Cmax)

  Cmax refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose

• Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose (AUC)

  The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose

• Cmax at Steady State During a Dosing Interval (Cmax,ss)

  Cmax,ss refers to the highest measured drug concentration, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.

  Blood samples were collected at on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.

• AUC From Time 0 to 24 Hours at Steady State(AUC(0-24),ss)

  AUC(0-24),ss is a measure of systemic drug exposure over 24 hours, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample, after multiple dose administration and after a steady state concentration has been reached.

  Blood samples were collected on Cycle 2, Day 1 and on Cycle 3, Day 1 for expansion cohort. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10 and 24h post-dose.

Secondary Outcomes (14)

• AUC From Time 0 to the Last Data Point > Lower Limit of Quantification (LLOQ) (AUC(0-tlast))

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose

• Area Under the Concentration vs. Time Curve From Zero to Infinity After Single (First) Dose Divided by Dose (AUC/D)

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose

• Maximum Observed Plasma Concentration After Single Dose Administration Divided by Dose (Cmax/D)

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose

• Time to Reach Maximum Observed Plasma Concentration (Tmax)

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.

• Half-life Associated With the Terminal Slope (T1/2)

  Blood samples were collected on Cycle 1, Day 1. Samples were drawn at the following time points: 0 h pre-dose, 0.5, 1, 2, 4, 8, 10, 24, and 48 h post-dose.

Other Outcomes (4)

• Tumor Progression in Dose Escalation Cohort

  From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)

• Tumor Progression in Expansion Cohort

  From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)

• Tumor Response in Dose Escalation Cohort

  From the screening visit of the first participant until the last evaluation of the final participant over 6 years later, assessed at the screening visit, end of cycle 2, end of each even cycle and during the final visit (end of treatment)

Study Arms (8)

Arm 1

EXPERIMENTAL

Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg

Arm 2

EXPERIMENTAL

Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg

Arm 3

EXPERIMENTAL

Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg

Arm 4

EXPERIMENTAL

Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg

Arm 5

EXPERIMENTAL

Drug: Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg

Arm 6

EXPERIMENTAL

Drug: HCC Child-Pugh A expansion cohort: Regorafenib 100 mg

Arm 7

EXPERIMENTAL

Drug: HCC Child-Pugh B expansion cohort: Regorafenib 100 mg

Arm 8

EXPERIMENTAL

Drug: NSCLC expansion cohort: Regorafenib 100 mg

Interventions

Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 20 mg DRUG

Participants in the dose-escalation cohort received a single 20 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 20 mg oral co-precipitate (CP) tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 1

Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 40 mg DRUG

Participants in the dose-escalation cohort received a single 40 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 40 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 2

Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 100 mg DRUG

Participants in the dose-escalation cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 3

Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 120 mg DRUG

Participants in the dose-escalation cohort received a single 120 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 120 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 4

Escalation cohort: Regorafenib (Stivarga, BAY73-4506) 140 mg DRUG

Participants in the dose-escalation cohort received a single 140 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 140 mg oral CP tablets was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 5

HCC Child-Pugh A expansion cohort: Regorafenib 100 mg DRUG

Hepatocellular carcinoma (HCC) Participants with Child Pugh A in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 6

HCC Child-Pugh B expansion cohort: Regorafenib 100 mg DRUG

Hepatocellular carcinoma (HCC) Participants with Child Pugh B in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 7

NSCLC expansion cohort: Regorafenib 100 mg DRUG

Non-small cell lung cancer (NSCLC) participants in the expansion cohort received a single 100 mg oral CP tablet of regorafenib on Day 1 of Cycle 1 followed by 1 day off treatment. On Day 3, once-daily continuous dosing with 100 mg oral CP tablets of regorafenib was initiated. A cycle was defined as 21 days. For Cycle 2 and subsequent cycles, regorafenib was administered once daily continuously on a 21-day cycle.

Arm 8

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years
• Patients with advanced, histologically or cytologically confirmed solid tumors, malignant lymphomas, or multiple myeloma refractory to any standard therapy
• Radiographical, hematological or clinically evaluable tumor
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Life expectancy of at least 12 weeks
• Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements:
• Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)
• Signed informed consent must be obtained prior to any study specific procedures

You may not qualify if:

• History of cardiac disease: congestive heart failure (CHF) \> New York Heart Association (NYHA) Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months or unstable angina or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 90 mmHg, despite optimal medical management
• History of HIV infection or chronic hepatitis B or C
• Active clinically serious infections (\> Grade 2 NCI Common Terminology Criteria for Adverse Events v3.0)
• Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry and is clinically stable with respect to the tumor at the time of study entry. Patients with brain metastases must not be undergoing acute steroid therapy or steroid taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
• Substance abuse, medical, psychological or social conditions that may interfere with the patient178s participation in the study or evaluation of the study results
• Radiotherapy to the target lesions within 3 weeks prior to Day 1, Cycle 1 (first dose of study drug). (Palliative radiotherapy will be allowed). Radiotherapy to the target lesions during study will be regarded as progressive disease
• Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors \[Ta, Tis and T1\] or any cancer curatively treated \> 3 years prior to study entry.

Sponsors & Collaborators

• Bayer: lead

Study Sites (5)

Unknown Facility

Los Angeles, California, 90095, United States

Location

Unknown Facility

Aurora, Colorado, 80045, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229-3307, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

regorafenib

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2010
• First Posted: May 5, 2010
• Study Start: February 1, 2007
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 18, 2015
• Results First Posted: January 19, 2015

Record last verified: 2015-11

Locations

US (5)