Clinical Study of BYM338 for the Treatment of Unintentional Weight Loss in Patients With Cancer of the Lung or the Pancreas

A Randomized, Double-blind, Placebo-controlled Multi-center Study of BYM338 for Treatment of Cachexia in Patients With Stage IV Non-small Cell Lung Cancer or Stage III/IV Adenocarcinoma of the Pancreas

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01433263

Enrollment

Registered

2011-09-13

Start date

2011-08-31

Completion date

2014-04-30

Last updated

2016-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cachexia

Keywords

Wasting syndrome, emaciation, lung cancer, adenocarcinoma, pancreatic cancer

Brief summary

A safety & efficacy clinical study of the investigational medicinal product BYM338 for the treatment of unintentional weight loss in patients with cancer of the lung or the pancreas

Interventions

DRUGBYM338 active drug

DRUGPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion criteria: 1. Patients must sign an informed consent before assessment 2. Patients with pathologically and/or clinically confirmed diagnosis of stage IV non-small (squamous or non-squamous) cell lung cancer (NSCLC) or stage III/IV adenocarcinoma of the pancreas. 3. Patients with stage IV NSCLC will be receiving or completed or discontinued standard chemotherapy or be chemotherapy-naive by choice. 4. Patients with stage III/IV pancreatic adenocarcinoma will be receiving standard chemotherapy or no chemotherapy. If patients are receiving chemotherapy, a change in chemotherapy is not expected. 5. Greater than or equal to 5% unintentional weight loss over the previous 3-6 months, not explained by simple starvation. Simple starvation is considered to be excluded when weight loss is not ameliorated by standard nutritional counseling and oral supplementation over a 2 week period. 6. Body mass index (BMI) ≤ 30 kg/m2. 7. Life expectancy of at least 4 months. 8. Able to communicate well and comply with the requirements of the study, including by phone and written logs. Key

Exclusion criteria

1. Patients who have received investigational anti-neoplastic therapy within 3 weeks of screening 2. Evidence of inadequate organ or brain function, as defined by lab tests and imaging 3. Patients with severe and/or uncontrolled medical conditions that could interfere with the study (e.g. heart conditions, high blood pressure, diabetes, infection) uncontrolled pain or any other non-stable illness 4. Pregnant or lactating women. 5. Women capable of becoming pregnant must use highly effective contraception during the study and for 8 weeks after stopping treatment. All female patients must have negative pregnancy test results throughout the study 6. Patients unwilling or unable to follow instructions. Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 8	Baseline, week 8	Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 8 was considered responders.

Secondary

Measure	Time frame	Description
Maximum Observed Serum Concentration (Cmax)	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 1 and Week 8	Blood samples for pharmacokinetic (PK) evaluation were drawn on Day 1 30mg/kg BYM338 (Core)or week 8 Late 30mg/kg BYM338 (when placebo subjects were rolled over to active). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.
Time to Reach the Maximum Concentration After Drug Administration (Tmax)	0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 1 and Week 8	Blood samples for pharmacokinetic (PK) evaluation were drawn on Day 1 30mg/kg BYM338 (Core)or week 8 Late 30mg/kg BYM338 (when placebo subjects were rolled over to active). Tmax was directly determined from the raw serum concentration-time data.
Percentage Change From Baseline in Total Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo: at Week 8	Baseline, Week 8	total lean body mass (LBM) is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(LBM at Visit - LBM at Baseline) / LBM at Baseline\] \* 100.
Percentage Change From Baseline of Bone Mineral Density (BMD) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo at Week 8	Baseline, Week 8	Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.
Percentage Change in Body Weight From Baseline at Week 7 and Week 9	Baseline, Week 7 and Week 9	Percentage Change in body weight from baseline in killograms (kg) at week 7 and week 9
Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Time Sedentary Taken Compared to Placebo at Week 4 and 7	Baseline, Week 4 and Week 7	Each patient was required to wear the ActivPal™ for a span of 6 days at Week 4 and Week 7 for patient home activity recording. The ActivPal™ was given to patients in clinic to wear for 6 consecutive days. The ActivPAL™ records periods spent sitting, standing and walking, sit-to-stand transitions, step count and rate of stepping (cadence) over a maximum period of 10 days with a fully charged new battery.
Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Time Standing Compared to Placebo at Week 4 and 7	Baseline, Week 4 and Week 7	Each patient was required to wear the ActivPal™ for a span of 6 days at Week 4 and Week 7 for patient home activity recording. The ActivPal™ was given to patients in clinic to wear for 6 consecutive days. The ActivPAL™ records periods spent sitting, standing and walking, sit-to-stand transitions, step count and rate of stepping (cadence) over a maximum period of 10 days with a fully charged new battery.
Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Time Stepping Compared to Placebo at Week 4 and 7	Baseline, Week 4 and Week 7	Each patient was required to wear the ActivPal™ for a span of 6 days at Week 4 and Week 7 for patient home activity recording. The ActivPal™ was given to patients in clinic to wear for 6 consecutive days. The ActivPAL™ records periods spent sitting, standing and walking, sit-to-stand transitions, step count and rate of stepping (cadence) over a maximum period of 10 days with a fully charged new battery.
Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Number of Steps Taken Compared to Placebo at Week 4 and 7	Baseline, Week 4 and Week 7	Each patient was required to wear the ActivPal™ for a span of 6 days at Week 4 and Week 7 for patient home activity recording. The ActivPal™ was given to patients in clinic to wear for 6 consecutive days. The ActivPAL™ records periods spent sitting, standing and walking, sit-to-stand transitions, step count and rate of stepping (cadence) over a maximum period of 10 days with a fully charged new battery.

Countries

Lithuania, Romania, Switzerland, United Kingdom, United States

Participant flow

Recruitment details

Core Phase single dose BYM338 30mg/kg i.v. active or placebo with 8week followup. Followup phase started Week 8 & patients on placebo in the Core Phase were given BYM338 & patients on BYM338 in Core Phase continued to be followed for an additional 8 weeks. Late BYM338 are patients who received Placebo during Core Phase and then BYM338 after Week 8.

Participants by arm

Arm	Count
30mg/kg BYM338	29
Placebo / Late 30mg/kg BYM338	28
Total	57

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	3	1
Overall Study	Death	5	3
Overall Study	Lost to Follow-up	0	1
Overall Study	Protocol Deviation	1	0
Overall Study	Withdrawal by Subject	10	7

Baseline characteristics

Characteristic	30mg/kg BYM338	Placebo / Late 30mg/kg BYM338	Total
Age, Continuous	62.8 years STANDARD_DEVIATION 10.17	61.5 years STANDARD_DEVIATION 10.74	62.1 years STANDARD_DEVIATION 10.38
Sex: Female, Male Female	9 Participants	6 Participants	15 Participants
Sex: Female, Male Male	20 Participants	22 Participants	42 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	19 / 29	19 / 28	12 / 19	2 / 3	13 / 21
serious Total, serious adverse events	18 / 29	4 / 28	7 / 19	1 / 3	7 / 21

Outcome results

Primary

Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 8

Thigh Muscle Volume (TMV) change was evaluated by a responder analysis. Patients whose loss of muscle TMV by MRI was no more than or equal to 2% at Week 8 was considered responders.

Time frame: Baseline, week 8

Population: Pharmacodynamics (PD) analysis set: Patients with evaluable PD parameter data. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. week 8

Arm	Measure	Value (MEAN)	Dispersion
30mg/kg BYM338	Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 8	2.0 Percentage Change of TMV	Standard Deviation 8.094
Placebo / Late 30mg/kg BYM338	Percentage Change From Baseline of Thigh Muscle Volume (TMV) by MRI Scan at Week 8	0.65 Percentage Change of TMV	Standard Deviation 8.239

Secondary

Maximum Observed Serum Concentration (Cmax)

Blood samples for pharmacokinetic (PK) evaluation were drawn on Day 1 30mg/kg BYM338 (Core)or week 8 Late 30mg/kg BYM338 (when placebo subjects were rolled over to active). PK parameters were calculated from plasma concentration-time data using non-compartmental methods.

Time frame: 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 1 and Week 8

Population: Pharmacokinetics (PK) analysis set: Patients with evaluable PK data.

Arm	Measure	Value (MEAN)	Dispersion
30mg/kg BYM338	Maximum Observed Serum Concentration (Cmax)	422 ng/ml	Standard Deviation 142
Placebo / Late 30mg/kg BYM338	Maximum Observed Serum Concentration (Cmax)	408 ng/ml	Standard Deviation 78.4

Secondary

Percentage Change From Baseline in Total Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo: at Week 8

total lean body mass (LBM) is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(LBM at Visit - LBM at Baseline) / LBM at Baseline\] \* 100.

Time frame: Baseline, Week 8

Arm	Measure	Value (MEAN)	Dispersion
30mg/kg BYM338	Percentage Change From Baseline in Total Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo: at Week 8	4.97 Percentage Change in LBM	Standard Deviation 7.537
Placebo / Late 30mg/kg BYM338	Percentage Change From Baseline in Total Lean Body Mass (LBM) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo: at Week 8	2.41 Percentage Change in LBM	Standard Deviation 4.625

Secondary

Percentage Change From Baseline of Bone Mineral Density (BMD) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo at Week 8

Bone Mineral Density (BMD)is measured by dual energy x-ray absorptiometry (DXA).Percent Change = \[(BMD at Visit - BMD at Baseline) / BMD at Baseline\] \* 100.

Time frame: Baseline, Week 8

Arm	Measure	Value (MEAN)	Dispersion
30mg/kg BYM338	Percentage Change From Baseline of Bone Mineral Density (BMD) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo at Week 8	0.51 Percentage Change in BMD	Standard Deviation 3.712
Placebo / Late 30mg/kg BYM338	Percentage Change From Baseline of Bone Mineral Density (BMD) by Dual-Energy X-ray Absorptiometery (DXA) Compared to Placebo at Week 8	0.14 Percentage Change in BMD	Standard Deviation 4.14

Secondary

Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Number of Steps Taken Compared to Placebo at Week 4 and 7

Each patient was required to wear the ActivPal™ for a span of 6 days at Week 4 and Week 7 for patient home activity recording. The ActivPal™ was given to patients in clinic to wear for 6 consecutive days. The ActivPAL™ records periods spent sitting, standing and walking, sit-to-stand transitions, step count and rate of stepping (cadence) over a maximum period of 10 days with a fully charged new battery.

Time frame: Baseline, Week 4 and Week 7