Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy

NCT02115464 | Terminated Phase 2 DMC

• 1 other identifier: OCOG-2014-ALMERA
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 7

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 with or without consolidation 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.

Conditions

Lung Cancer

Keywords

Metformin; Non-small cell lung cancer; Locally advanced; Chemo-radiotherapy; Lung cancer treatment

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Progression free survival illustrates loco-regional disease control and freedom from distant metastasis

  12 months

Secondary Outcomes (4)

• Overall survival

  18-24 months

• Time to loco-regional progression

  18-24 months

• Distant progression-free survival

  18-24 months

• Toxicities

  12 months plus 30 days

Study Arms (2)

Metformin plus Chemo-radiotherapy

EXPERIMENTAL

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 or without consolidation with standard radiotherapy of 60-63 Gy for 6 weeks.

Drug: Metformin plus Chemo-radiotherapy

Chemo-radiotherapy

ACTIVE COMPARATOR

Concurrent cisplatin based chemotherapy with or without consolidation and radiotherapy of 60-63 Gy for 6 weeks.

Radiation: Chemo-radiotherapy

Interventions

Metformin plus Chemo-radiotherapy DRUG

Metformin 2000 mg a day for 12 months plus cisplatin-based chemotherapy with or without consolidation with standard radiotherapy of 60-63 Gy for 6 weeks.

Also known as: Metformin Hydrochloride

Metformin plus Chemo-radiotherapy

Chemo-radiotherapy RADIATION

Cisplatin-based chemotherapy with or without consolidation with standard radiotherapy of 60-63 Gy for 6 weeks.

Chemo-radiotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>/=18 to \</= 80 years of age.
• 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.
• Non-metastatic disease staged by: CT-chest and upper abdomen, brain MRI or contrast-enhanced CT within 12 weeks and physical examination and whole body FDG-PET/CT scan within 8 weeks prior to study randomization.

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status \>2.
• More than 10% weight loss in the past 3 months.
• Diabetic patient or anyone currently taking Metformin, insulin or other anti-hyperglycemic therapy.
• 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.
• Complete Blood Count (CBC) and biochemical renal and liver function profiles that do not permit chemotherapy treatment (as per institutional standard of care).
• Fasting blood sugar levels of \>/= 7.0 mmol per litre (within the last 12 weeks).
• Prior systemic chemotherapy for lung cancer.
• Prior radiotherapy that would overlap with the planned treatment area.
• 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).
• Known Acquired Immune Deficiency Syndrome (AIDS).
• 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,

Sponsors & Collaborators

• Ontario Clinical Oncology Group (OCOG): lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (7)

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

Location

Walker Family Cancer Centre - Niagara Health System

St. Catharines, Ontario, Canada

Location

Montreal General Hospital - McGill

Montreal, Quebec, Canada

Location

Related Publications (1)

• Tsakiridis T, Pond GR, Wright J, Ellis PM, Ahmed N, Abdulkarim B, Roa W, Robinson A, Swaminath A, Okawara G, Wierzbicki M, Valdes M, Levine M. Metformin in Combination With Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1333-1341. doi: 10.1001/jamaoncol.2021.2328.

  PMID: 34323924 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Metformin

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Theodoros Tsakiridis, MD

  Juravinski Cancer Centre, Hamilton, Ontario, Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: December 17, 2014
• Primary Completion: March 9, 2020
• Study Completion: April 21, 2020
• Last Updated: April 22, 2020

Record last verified: 2020-04

Locations

CA (7)