Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy | RxWiki

Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy

Overview[ - collapse ][ - ]

Purpose	ALMERA is a randomized, phase II, open label study in patients with locally advanced non-small cell lung cancer (NSCLC) which will compare standard radiotherapy plus concurrent chemotherapy versus the same treatment plus concurrent Metformin continuing for 12 months. Metformin is a well tolerated and inexpensive drug that has the potential to improve cancer patient outcomes.
Condition	Lung Cancer
Intervention	Drug: Metformin plus Chemo-radiotherapy Radiation: Chemo-radiotherapy
Phase	Phase 2
Sponsor	Ontario Clinical Oncology Group (OCOG)
Responsible Party	Ontario Clinical Oncology Group (OCOG)
ClinicalTrials.gov Identifier	NCT02115464
First Received	April 14, 2014
Last Updated	April 14, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	April 14, 2014
Last Updated Date	April 14, 2014
Start Date	June 2014
Estimated Primary Completion Date	December 2017
Current Primary Outcome Measures	Progression free survival [Time Frame: 12 months] [Designated as safety issue: No]Progression free survival illustrates loco-regional disease control and freedom from distant metastasis
Current Secondary Outcome Measures	Overall survival [Time Frame: 18-24 months] [Designated as safety issue: No]Overall survival will be defined from the date of randomization until the date of death due to any cause. Time to loco-regional progression [Time Frame: 18-24 months] [Designated as safety issue: No]Time to loco-regional progression is defined from the date of randomization until the date of confirmed loco-regional progression Distant progression-free survival [Time Frame: 18-24 months] [Designated as safety issue: No]Distant progression-free survival is defined from the date of randomization until the date of distant progression, or death due to any cause. Toxicities [Time Frame: 12 months plus 30 days] [Designated as safety issue: Yes]Adverse event reporting period begins from the time of the first dose of Metformin and ends 30 days after the last dose. Only adverse events assessed as Grade 3 or higher will be documented.

Descriptive Information[ + expand ][ + ]

Brief Title	Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy
Official Title	A Phase II Study to Investigate a Combination of Metformin With Chemo-Radiotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer
Brief Summary	ALMERA is a randomized, phase II, open label study in patients with locally advanced non-small cell lung cancer (NSCLC) which will compare standard radiotherapy plus concurrent chemotherapy versus the same treatment plus concurrent Metformin continuing for 12 months. Metformin is a well tolerated and inexpensive drug that has the potential to improve cancer patient outcomes.
Detailed Description	This is a randomized, phase II, open label study in patients with locally advanced NSCLC which will compare standard RT (60-63 Gy for 6 weeks) plus concurrent Cisplatin-based chemotherapy (CRT) (standard arm) vs the same CRT plus treatment with Metformin concurrent with CRT and continuing for a total of 12 months (experimental arm). Ninety-four eligible and consenting patients will be randomized to one of the two treatment arms. Patients randomized to the experimental arm will receive Metformin (2000 mg/day) for a period of 12 months. Patients will be continuously evaluated for toxicity, will be assessed weekly at clinic visits during concurrent CRT treatment and at follow up clinic visits at 3, 6, 9 and 12 months (from the date of randomization). Disease progression will be evaluated every 3 months for up to 12 months. All patients will be followed for up to 24 months (2 years) for survival. The primary objective of this study is to determine the effect of Metformin on the proportion of patients free of disease progression at 12 months after initiation of drug treatment.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Lung Cancer
Intervention	Drug: Metformin plus Chemo-radiotherapy Metformin 2000 mg a day for 12 months plus cisplatin-based chemotherapy with standard radiotherapy of 60-63 Gy for 6 weeks. Other Names: Metformin HydrochlorideRadiation: Chemo-radiotherapy Cisplatin-based chemotherapy with standard radiotherapy of 60-63 Gy for 6 weeks.
Study Arm (s)	Experimental: Metformin plus Chemo-radiotherapy Metformin orally 500 mg twice daily for the first week, 1500 mg a day in week 2 and 2000 mg a day at week 3 and then for a period of 12 months. Cisplatin-based chemotherapy with standard radiotherapy of 60-63 Gy for 6 weeks. Active Comparator: Chemo-radiotherapy Concurrent cisplatin based chemotherapy and radiotherapy of 60-63 Gy for 6 weeks.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Not yet recruiting
Estimated Enrollment	94
Estimated Completion Date	December 2017
Estimated Primary Completion Date	December 2015
Eligibility Criteria	Inclusion Criteria: 1. Age >/=18 to 2. Unresected and pathologically (histologic) proven Stage 3a or Stage 3b NSCLC of adenocarcinoma, squamous cell, large cell or mixed histology, diagnosed within three months of study randomization. 3. Non-metastatic disease staged by: physical examination, CT-chest and upper abdomen, brain MRI or contrast-enhanced CT and whole body Fluorodeoxyglucose (FDG)-PET/CT scan within two months of study randomization. Exclusion Criteria: 1. Eastern Cooperative Oncology Group (ECOG) performance status >2. 2. More than 10% weight loss in the past 3 months. 3. Diabetic patient or anyone currently taking Metformin, insulin or other anti-hyperglycemic therapy. 4. Pulmonary Function Test (PFTs) (within the last 12 weeks) with Forced Expiratory Volume (FEV)1 < 1.2 litres per second or less than 50% of predicted. 5. Complete Blood Count (CBC) and biochemical renal and liver function profiles that do not permit chemotherapy treatment (as per institutional standard of care). 6. Fasting blood sugar levels of >/= 7.0 mmol per litre. 7. Prior systemic chemotherapy for lung cancer. 8. Prior radiotherapy that would overlap with the planned treatment area. 9. Prior invasive malignancy within the past 3 years (except non-melanomatous skin cancer non-invasive carcinoma in-situ of the breast, oral cavity or cervix). 10. Known Acquired Immune Deficiency Syndrome (AIDS). 11. Patients with increased risk for lactic acidosis: - severe congestive heart failure (NYHA: class III or IV), - history of metabolic acidosis, - alcoholic intake of > 3 drinks daily, - severe liver disease, - renal failure 12. Known hypersensitivity or allergy to Metformin. 13. Known pregnancy or lactating female patient. 14. Geographic inaccessibility for follow-up. 15. Inability to provide informed consent.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Kathryn Cline, BSc clinek@mcmaster.ca
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT02115464
Other Study ID Numbers	OCOG-2014-ALMERA
Has Data Monitoring Committee	Yes
Information Provided By	Ontario Clinical Oncology Group (OCOG)
Study Sponsor	Ontario Clinical Oncology Group (OCOG)
Collaborators	Canadian Institutes of Health Research (CIHR)
Investigators	Principal Investigator: Theodoros Tsakiridis, MD Juravinski Cancer Centre, Hamilton, Ontario, Canada
Verification Date	April 2014