Open-Label, Pilot Phase I/II Study of the Efficacy and Safety of Concomitant Megestrol + Formoterol in Patients with Cachexia and Advanced Malignancy
- Conditions
- Cancer-related cachexia, also known as Cancer Anorexia-Cachexia Syndrome (CACS)MedDRA version: 9.1 Level: LLT Classification code 10064015 Term: Cancer cachexia
- Registration Number
- EUCTR2008-008857-53-GB
- Lead Sponsor
- Acacia Pharma Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 13
1.Age greater than 18 years.
2.Tumour situation: any type of advanced (defined as locally recurrent or metastatic), incurable solid tumour, expected to remain without rapid progression in the next 8 weeks, and not likely to require new anti-neoplastic treatment, large field radiotherapy or major surgery.
3.Cachexia: Involuntary loss of weight of greater than or equal to 2% in 2 months or greater than or equal to 5% in 6 months, without (or with successfully treated) secondary causes of impaired oral nutritional intake (simple starvation).
4.No simple starvation: Participants must not be prevented from eating by severe structural barriers in the upper gastrointestinal tract or bowel obstruction. Participants with impaired ability to eat because of severe tumour caused symptoms (such as severe early satiety, anorexia, or taste alterations), but no severe structural damage of the gastrointestinal tract, are eligible.
5.Life expectancy greater than or equal to 3 months, in the judgment of the investigator.
6.Performance status less than or equal to 2.
7.Concomitant anti-neoplastic chemotherapy: allowed provided unchanged for previous 4 weeks and not causing = Grade II nausea, vomiting, mucositis or other GI tract toxicity.
8.Laboratory test results within these ranges: absolute neutrophil count = 1.5 x 109/L, serum potassium > 3.5mmol/L, serum creatinine = 180µmol, total bilirubin = 25µmol and AST (SGOT) and ALT (SGPT) = 2 x ULN or = 5 x ULN if hepatic metastases are present.
9. Diastolic blood pressure <95 mmHg.
10.No other trial: Participant has not participated in any other clinical trial within previous 28 days.
11.Women: A negative pregnancy test & effective contraception are mandatory for women of child-bearing age.
12.Gastrectomy: Participants with history of gastrectomy are eligible.
13.Voluntarily signed and dated Research Ethics Committee-approved consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. BMI > 30kg/m2, or gross fluid retention, including ascites (but presence of pleural effusion will not exclude the patient).
2. Parenteral nutrition.
3. High risk of failure to complete the study, as defined by laboratory finding of both Creactive protein > 10mg/L and white blood cell count > 11 x 109/L.
4. Uncontrolled diabetes mellitus or hyperthyroidism.
5. History of ongoing, significant ischaemic heart disease (specifically: myocardial infarction in the previous 3 months; coronary intervention in the previous 3 months; or unstable angina); clinically significant cardiac arrhythmias, especially third degree atrioventricular block; severe cardiac decompensation; idiopathic subvalvular aortic stenosis; hypertrophic obstructive cardiomyopathy; thyrotoxicosis; known or suspected prolongation of the QT interval (QTc > 0.44 sec for men or 0.46 sec for women).
6. An episode of lower limb thrombophlebitis within the previous two months; or a deep vein thrombosis within the previous six months; or a current documented prothrombotic tendency, e.g., protein C deficiency, marked thrombocythaemia.
7. Participants currently on treatment (or having been treated in the two weeks prior to screening) with any of the following agents or drug classes: other ß2-agonists or ß2-antagonists, unless given by the inhaled route, or other route in which systemic exposure is expected to be low; agents specifically intended to increase appetite or provide anabolic stimulus to muscles, e.g., growth hormone, anabolic steroids.
8. Participants with cerebral metastases or prophylactic whole brain irradiation for
possible cerebral metastases.
9. Known hypersensitivity to megestrol acetate or formoterol fumarate.
10. Known positive for HIV or infectious hepatitis B or C.
11. Pregnant or breast feeding females.
12. The presence in both legs of either a metal knee or metal hip implant.
13. Any of the standard contra-indications to MRI scanning.
14. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of megestrol and formoterol, given concomitantly, in adult patients with active cachexia associated with advanced malignancy and not caused by simple starvation.;Secondary Objective: To assess the safety of megestrol and formoterol, given concomitantly, in patients with advanced malignancy and active cachexia.;<br> Primary end point(s): Muscle response”: outcome of quadriceps size and function after treatment compared with baseline.<br> -Quadriceps muscle size, measured as volume and cross-sectional area (CSA) at mid-point, by MRI scanning of thigh, with digital fat subtraction;<br> -Muscle function: (maximal voluntary isometric knee extensor strength, measured using a specialised strength-testing chair; and average lower limb power output, measured using a Nottingham Power Rig.<br>
- Secondary Outcome Measures
Name Time Method