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Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy (ALMERA)

Primary Purpose

Lung Cancer

Status
Terminated
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin plus Chemo-radiotherapy
Chemo-radiotherapy
Sponsored by
Ontario Clinical Oncology Group (OCOG)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Metformin, Non-small cell lung cancer, Locally advanced, Chemo-radiotherapy, Lung cancer treatment

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age >/=18 to </= 80 years of age.
  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: 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.

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 (within the last 12 weeks).
  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.

Sites / Locations

  • Cross Cancer Institute
  • CancerCare Manitoba
  • Juravinski Cancer Centre
  • Cancer Centre of Southeastern Ontario at Kingston General Hospital
  • Grand River Regional Cancer Centre
  • Walker Family Cancer Centre - Niagara Health System
  • Montreal General Hospital - McGill

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Metformin plus Chemo-radiotherapy

Chemo-radiotherapy

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival
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 to loco-regional progression is defined from the date of randomization until the date of confirmed loco-regional progression
Distant progression-free survival
Distant progression-free survival is defined from the date of randomization until the date of distant progression, or death due to any cause.
Toxicities
The adverse event reporting period begins from the time of randomization and ends 30 days after the last treatment (concurrent chemo-radiotherapy plus or minus Metformin). Only adverse events assessed as Grade 3 or higher will be documented.

Full Information

First Posted
April 14, 2014
Last Updated
April 21, 2020
Sponsor
Ontario Clinical Oncology Group (OCOG)
Collaborators
Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT02115464
Brief Title
Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy
Acronym
ALMERA
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
The accrual rate was not high enough to reach the target sample size.
Study Start Date
December 17, 2014 (Actual)
Primary Completion Date
March 9, 2020 (Actual)
Study Completion Date
April 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ontario Clinical Oncology Group (OCOG)
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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) with or without consolidation (standard arm) vs the same CRT with or without consolidation 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 with or without consolidation 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
Metformin, Non-small cell lung cancer, Locally advanced, Chemo-radiotherapy, Lung cancer treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin plus Chemo-radiotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Chemo-radiotherapy
Arm Type
Active Comparator
Arm Description
Concurrent cisplatin based chemotherapy with or without consolidation and radiotherapy of 60-63 Gy for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Metformin plus Chemo-radiotherapy
Other Intervention Name(s)
Metformin Hydrochloride
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Chemo-radiotherapy
Intervention Description
Cisplatin-based chemotherapy with or without consolidation with standard radiotherapy of 60-63 Gy for 6 weeks.
Primary Outcome Measure Information:
Title
Progression free survival
Description
Progression free survival illustrates loco-regional disease control and freedom from distant metastasis
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Overall survival
Description
Overall survival will be defined from the date of randomization until the date of death due to any cause.
Time Frame
18-24 months
Title
Time to loco-regional progression
Description
Time to loco-regional progression is defined from the date of randomization until the date of confirmed loco-regional progression
Time Frame
18-24 months
Title
Distant progression-free survival
Description
Distant progression-free survival is defined from the date of randomization until the date of distant progression, or death due to any cause.
Time Frame
18-24 months
Title
Toxicities
Description
The adverse event reporting period begins from the time of randomization and ends 30 days after the last treatment (concurrent chemo-radiotherapy plus or minus Metformin). Only adverse events assessed as Grade 3 or higher will be documented.
Time Frame
12 months plus 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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, renal failure Known hypersensitivity or allergy to Metformin. Known pregnancy or lactating female patient. Geographic inaccessibility for follow-up. Inability to provide informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Theodoros Tsakiridis, MD
Organizational Affiliation
Juravinski Cancer Centre, Hamilton, Ontario, Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
Country
Canada
Facility Name
CancerCare Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston General Hospital
City
Kingston
State/Province
Ontario
Country
Canada
Facility Name
Grand River Regional Cancer Centre
City
Kitchener
State/Province
Ontario
Country
Canada
Facility Name
Walker Family Cancer Centre - Niagara Health System
City
St. Catharines
State/Province
Ontario
Country
Canada
Facility Name
Montreal General Hospital - McGill
City
Montreal
State/Province
Quebec
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
34323924
Citation
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.
Results Reference
derived

Learn more about this trial

Advanced Lung Cancer Treatment With Metformin and Chemo-Radiotherapy

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