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

Study Overview
=================
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

Official Title
-----------------
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

Conditions
-----------------
Cachexia

Intervention / Treatment
-----------------
* Drug: BYM338 active drug
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion criteria: Patients must sign an informed consent before assessment 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. Patients with stage IV NSCLC will be receiving or completed or discontinued standard chemotherapy or be chemotherapy-naive by choice. 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. 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. Body mass index (BMI) ≤ 30 kg/m2. Life expectancy of at least 4 months. Able to communicate well and comply with the requirements of the study, including by phone and written logs. Key Exclusion criteria: Patients who have received investigational anti-neoplastic therapy within 3 weeks of screening Evidence of inadequate organ or brain function, as defined by lab tests and imaging 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 Pregnant or lactating women. 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 Patients unwilling or unable to follow instructions. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30mg/kg BYM338<br> | Drug: BYM338 active drug<br> <br> |
| Placebo Comparator: Placebo / late 30mg/kg BYM338<br> | Drug: BYM338 active drug<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Body Weight From Baseline at Week 7 and Week 9 | Percentage Change in body weight from baseline in killograms (kg) at week 7 and week 9 | Baseline, Week 7 and Week 9 | 
| 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. | 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 1 and Week 8 | 
| Time to Reach the Maximum Concentration After Drug Administration (Tmax) | 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. | 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hours post-dose on Day 1 and Week 8 | 
| 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. | Baseline, Week 8 | 
| 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. | Baseline, Week 8 | 
| 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. | Baseline, Week 4 and Week 7 | 
| Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Time Sedentary 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. | Baseline, Week 4 and Week 7 | 
| Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Time Standing 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. | Baseline, Week 4 and Week 7 | 
| Percentage Change From Baseline of Physical Activity Levels (Using the ActivPAL™ Device) Time Stepping 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. | Baseline, Week 4 and Week 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Wasting syndrome, emaciation, lung cancer, adenocarcinoma, pancreatic cancer