A safety and 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

• Register: EUCTR
• Last refreshed on: 16 June 2014
• Main ID: EUCTR2010-024342-30-GB
• Date of registration: 07/06/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A safety and 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
• Scientific 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
• Date of first enrolment: 20/07/2011
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024342-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Lithuania, Switzerland, United Kingdom, United States

Contacts

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceutials UK Ltd

• Name: Medical Information Services
• Affiliation: Novartis Pharmaceutials UK Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent must be obtained before any assessment is performed.

2. Adult men and women >18 years of age 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 chemo-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.Patients receiving chemotherapy must be tolerating it with respect to nausea/vomiting/anorexia symptoms and demonstrate adequate dietary intake before starting the study drug.

6. =5% unintentional weight loss from patient reported pre-illness weight at Screening or Baseline visits, occuring over the previous 3-6 months and not explained by simple starvation.

7. In patients with 2+ or greater pitting edema of the legs, documented weight loss > 2% over 4 weeks, not due to diuretic therapy, is acceptable.

8. Body mass index = 30 kg/m2. Body mass index = mass (kg)/(height in meters)2 at screening.

9. Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2 at screening and baseline.

10. Life expectancy of >4 months based on judgment of enrolling physician.

11. Literate and able to communicate well with the investigator and team depending on country of study, to understand and comply with the requirements of the study including by phone encounters and written logs.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1. Patients who have received investigational anti-neoplastic therapy within 3 weeks of screening, or for any other limitation of participation in an investigational trial based on local regulations.

2. a. Expected to receive Avastin (bevacizumab) therapy or have received within 8 weeks of the Baseline visit.

2.b. Received radiation therapy within 4 weeks of the Baseline visit, or expected to require radiation therapy during the 8 week Core phase of the study.

2.c. Major surgery within the past 3 weeks prior to the Screening visit.

2.d. Use of oral corticosteroids >20 mg/d prednisone equivalent, unless used in pulse form for chemotherapy-related symptoms such as nausea/vomiting.

2.e. Within 4 weeks of baseline visit, use of medications for weight loss (incl. megestrol acetate, androgens, beta agonists).

3. Severe nausea/vomiting/anorexia/mucositis/steatorrhea/uncontrolled pain or gastrointestinal disorder, intestinal or biliary obstruction, or other reason that causes enteral energy intake <20 kcal/kg/day and protein intake of <0.6 g/kg/d (estimated from 2-day food record at screening). Dietary intake may be ascertained again within 1 to 2 weeks after intensive nutritional counseling.

4. Evidence of inadequate organ function, as defined by the following parameters at screening: Bone marrow: ANC <1.0 x 10_9/L, platelets <75 x 10_9/L; Hepatic function: serum total bilirubin >3 x ULN, AST and ALT >5 x ULN; Pancreatic function: serum amylase or lipase >5 x ULN and evidence of uncontrolled exocrine pancreatic dysfunction (pain, nausea, vomiting, steatorrhea, radiographic evidence of pancreatic or common bile duct obstruction). For patients with pancreatic adenocarcinoma, imaging report of moderate-severe bile duct dilatation; Renal function: GFR <30 mL/min, estimated from the MDRD equation; CNS: Evidence of clinically significant brain metastases requiring high dose corticosteroid therapy or causing uncontrolled seizures, mental status changes, anorexia, nausea or vomiting.

5. At screening and baseline, vital signs will be assessed in the supine position after subject has rested for at least 3 minutes and again after three (3) minutes in the standing position. Vital signs outside the ranges specified below are exclusionary: Oral body temperature: <35.0 or >38 °C; (>38.5 °C if evaluation for infection is negative and fever is thought to be related to tumor). Systolic blood pressure: <70 mm Hg. Symptomatic orthostatic hypotension.

6. Patients with concurrent severe and/or uncontrolled medical conditions that could compromise participation in the study (e.g. myocardial infarction within the past 3 months; congestive heart failure requiring medical treatment; uncontrolled hypertension or diabetes mellitus; severe pancreatitis; clinically significant neurologic or psychiatric disorder; immunodeficiency, active or uncontrolled infection), uncontrolled pain, other non-stable comorbidities.

7. Pregnant or lactating women.

8. Women of child-bearing potential must use highly effective contraception during the study and for 14 weeks after stopping treatment. Highly effective contraception is defined as either: a. Total abstinence [Periodic abstinence and withdrawal are not acceptable]. b. Surgical bilateral oophorectomy with/without hysterectomy or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status has been confirmed by follow up hormone lev

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Condition of cachexia in adults with stage IV metastatic non-small cell lung cancer or stage III/IV pancreatic adenocarcinoma.
MedDRA version: 14.1 Level: LLT Classification code 10064015 Term: Cancer cachexia System Organ Class: 100000004861

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: BYM338
Product Code: BYM338
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: BYM338
Other descriptive name: Human Monoclonal Antibody blocking ActRIIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8.

Main Objective: To assess the preliminary efficacy of a single intravenous dose of BYM338 in increasing thigh muscle volume as assessed by Magnetic Resonance Imaging compared to placebo.

Primary end point(s): Superiority of BYM338 compared to placebo in thigh muscle volume.

Secondary Objective: To assess the safety and tolerability of intravenous BYM338 in this patient population.

To assess the preliminary efficacy of intravenous BYM338 in treating unintentional weight loss compared to placebo.

To obtain preliminary pharmacokinetic data for intravenous BYM338 in this patient population.

To assess the preliminary efficacy of intravenous BYM338 in improving total lean body mass and total bone mineral density by Dual-Energy X-ray Absorptiometery compared to placebo.

To assess the preliminary efficacy of a single intravenous dose of BYM338 in improving daily physical activity levels (using the ActivPAL™ device) compared to placebo.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 8.

Secondary end point(s): Safety and tolerability of a single intravenous dose of BYM338.

Preliminary efficacy of a single intravenous dose of BYM338 in treating unintentional weight loss.

Preliminary pharmacokinetic data of a single intravenous dose of BYM338.

Improving total lean body mass and bone mineral density.

Preliminary efficacy of a single intravenous dose of BYM338 in improving daily physical activity levels (using the ActivPAL™ device).

Secondary ID(s)

Not applicable

CBYM338X2202

Source(s) of Monetary Support

Novartis Pharma Services AG