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

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

Study Overview

• Status: Completed
• Conditions: Cachexia
• Intervention / Treatment: Drug: Placebo; Drug: BYM338 active drug

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Lithuania
  • Vilnius, Lithuania, LT 08661
    • Novartis Investigative Site
• Romania
  • Bucharest, Romania, Sector 5
    • Novartis Investigative Site
• Switzerland
  • St. Gallen, Switzerland, 9007
    • Novartis Investigative Site
• United Kingdom
  • Edinburgh, United Kingdom, EH10 5HF
    • Novartis Investigative Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Novartis Investigative Site
  • Florida
    • Tampa, Florida, United States, 33647
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60611-3308
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Novartis Investigative Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • Novartis Investigative Site
  • Texas
    • San Antonio, Texas, United States, 78217
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 30mg/kg BYM338	Drug: BYM338 active drug
Placebo Comparator: Placebo / late 30mg/kg BYM338	Drug: Placebo; Drug: BYM338 active drug

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: August 24, 2011
• First Submitted That Met QC Criteria: September 9, 2011
• First Posted (Estimate): September 13, 2011

Study Record Updates

• Last Update Posted (Estimate): March 2, 2016
• Last Update Submitted That Met QC Criteria: February 2, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: lung cancer; pancreatic cancer; adenocarcinoma; emaciation; Wasting syndrome
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Emaciation; Weight Loss; Wasting Syndrome; Cachexia
• Other Study ID Numbers: CBYM338X2202