Observational Study of Incidence Rates of Esophageal Cancer in Women Taking Medications for the Prevention or Treatment of Osteoporosis (MK-0217A-352)

An observational study of Esophageal Cancer and Squamous Cell Carcinoma, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This is a 2-phase retrospective database study, using both case-cohort and inception (intention-to-treat) cohort analyses to evaluate any association between oral treatments for osteoporosis and the risk of esophageal cancer in women. Read more about this study

Who is it for?: Ages 55 years and older, women only
Conditions the study is for: Esophageal Cancer, Squamous Cell Carcinoma, Adenocarcinoma
What is being tested?: Alendronate, Etidronate and Ibandronate
Type of treatment: Pill or oral medicine, Injection or infusion
How many people: 684,815 participants
Where: No sites listed yet
Study dates: 26 Feb 2010to 16 Feb 2012
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 years and older
Women only
No healthy volunteers
Adult, Older adult

Study population: Women who have at least two years of experience in the GPRD and are 55 or older between 1996 and 2008; all cases of esophageal cancer were identified and matched to all women in the comparison sample (all women with same year of birth drawn from the random subsample of 25,000).

Who may be able to join

Cases:
Women in the database aged 55 or older between 1996 and 2008 with diagnosis of esophageal cancer
Comparator Controls:
Each case was matched to all women in the random subcohort of 25,000 who had the same year of birth as the case and were in the database at the time of diagnosis.

Who cannot join

Women with diagnosis of any other cancer or Paget's Disease or who have received oral or intravenous steroids before the index date

About this study

Official title: The Risk of Esophageal Cancer in Relation to the Treatment and Prevention of Osteoporosis in Women

Conditions: Esophageal Cancer, Squamous Cell Carcinoma, Adenocarcinoma
Being tested: Alendronate, Etidronate, Ibandronate, Risedronate, Raloxifene
Medical subject headings: Esophageal Neoplasms, Carcinoma, Squamous Cell, Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AlendronateDrug
Also called FOSAMAX®
EtidronateDrug
Also called DIDRONEL®
IbandronateDrug
Also called BONIVA®
RisedronateDrug
Also called ACTONEL®, ATELVIA®
RaloxifeneDrug
Also called EVISTA®

Study groups in NCT01077817
Study group	Role	What they receive
Esophageal Cancer Cases		Participants with any United Kingdom General Practice Research Database (GPRD) Medical code for esophageal cancer (cases). Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review. Receives: Drug: Alendronate; Drug: Etidronate; Drug: Ibandronate; Drug: Risedronate; Drug: Raloxifene
Comparison Sample (Case-Cohort)		Participants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes. Receives: Drug: Alendronate; Drug: Etidronate; Drug: Ibandronate; Drug: Risedronate; Drug: Raloxifene
Non-treated Comparators		Participants who did not initiate treatment of osteoporosis with a study drug
Alendronate		Participants initiating treatment for osteoporosis with alendronate Receives: Drug: Alendronate
Etidronate		Participants initiating treatment for osteoporosis with etidronate Receives: Drug: Etidronate
Ibandronate		Participants initiating treatment for osteoporosis with ibandronate Receives: Drug: Ibandronate
Risedronate		Participants initiating treatment for osteoporosis with risedronate Receives: Drug: Risedronate
Raloxifene		Participants initiating treatment for osteoporosis with raloxifene Receives: Drug: Raloxifene

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis)
To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.
Measured: Exposure to study drug at least 720 days before disease onset
Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis)
To assess the relative risk of esophageal cancer associated with osteoporosis study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene), initiators of osteoporosis drugs and non-initiators (comparators, women sharing match criteria with the initiator) entered an inception cohort for every three-month period, beginning in the first quarter of 1996. Assignment to study drug exposure group remained fixed from the start of follow-up, analogous to an intent-to-treat analysis. The risk of esophageal cancer among initiators of study drug compared to non-initiators of study drug was estimated through calculation of a hazard ratio. For calculation of 721+ day hazard ratios, only esophageal cancer cases occurring at least 721 days from initiation of study drug were used. For calculation of 1441+ day hazard ratios, only esophageal cancer cases occurring at least 1441 days from initiation of study drug were used.
Measured: Up to approximately 7.3 years of follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Feb 201016 Feb 2012

First posted1 Mar 2010 (estimated)
Study start26 Feb 2010
Primary completion16 Feb 2012
Study completion16 Feb 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Esophageal CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Retrospective
Enrolment: 684,815 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01077817
Sponsor's protocol ID: 0217A-352
Other IDs: EP02001.029, 2010_015
Status last verified: Feb 2022
First submitted: 26 Feb 2010
Last updated: 3 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Esophageal Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Risk of Esophageal Cancer in Relation to the Treatment and Prevention of Osteoporosis in Women
ClinicalTrials.gov ID: NCT01077817
Acronym / sponsor ID: 0217A-352
Conditions: Esophageal Cancer, Squamous Cell Carcinoma, Adenocarcinoma
Study type: Observational
Recruitment status: Completed
Enrolment: 684,815 participants (actual)
Lead sponsor: Organon and CoIndustry (pharma, biotech, devices)
Collaborators: World Health Information Science Consultants, LLC
Study start: 26 Feb 2010 (actual)
Primary completion: 16 Feb 2012 (actual)
Study completion: 16 Feb 2012 (actual)
First posted: 1 Mar 2010 (estimated)
Results: Posted 1 May 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Observational model: Cohort
Time perspective: Retrospective
Number of arms: 8

Arm	Type	Receives
Esophageal Cancer Cases	–	Drug: Alendronate, Drug: Etidronate, Drug: Ibandronate, Drug: Risedronate, Drug: RaloxifeneParticipants with any United Kingdom General Practice Research Database (GPRD) Medical code for esophageal cancer (cases). Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.
Comparison Sample (Case-Cohort)	–	Drug: Alendronate, Drug: Etidronate, Drug: Ibandronate, Drug: Risedronate, Drug: RaloxifeneParticipants who were matched to cases by age and membership in the GPRD on the case's onset date, and had not experienced any form of esophageal cancer or Paget's Disease and had not received oral or intravenous steroids or chemotherapy or radiotherapy, as indicated by GPRD codes.
Non-treated Comparators	–	–Participants who did not initiate treatment of osteoporosis with a study drug
Alendronate	–	Drug: AlendronateParticipants initiating treatment for osteoporosis with alendronate
Etidronate	–	Drug: EtidronateParticipants initiating treatment for osteoporosis with etidronate
Ibandronate	–	Drug: IbandronateParticipants initiating treatment for osteoporosis with ibandronate
Risedronate	–	Drug: RisedronateParticipants initiating treatment for osteoporosis with risedronate
Raloxifene	–	Drug: RaloxifeneParticipants initiating treatment for osteoporosis with raloxifene

Who may qualify

Ages: 55 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Women who have at least two years of experience in the GPRD and are 55 or older between 1996 and 2008; all cases of esophageal cancer were identified and matched to all women in the comparison sample (all women with same year of birth drawn from the random subsample of 25,000).

Key inclusion criteria (4 listed)

Cases:
Comparator Controls:

Key exclusion criteria (1 listed)

Women with diagnosis of any other cancer or Paget's Disease or who have received oral or intravenous steroids before the index date

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AlendronateAlso: FOSAMAX®	Drug	Alendronate, Comparison Sample (Case-Cohort), Esophageal Cancer Cases
EtidronateAlso: DIDRONEL®	Drug	Comparison Sample (Case-Cohort), Esophageal Cancer Cases, Etidronate
IbandronateAlso: BONIVA®	Drug	Comparison Sample (Case-Cohort), Esophageal Cancer Cases, Ibandronate
RisedronateAlso: ACTONEL®, ATELVIA®	Drug	Comparison Sample (Case-Cohort), Esophageal Cancer Cases, Risedronate
RaloxifeneAlso: EVISTA®	Drug	Comparison Sample (Case-Cohort), Esophageal Cancer Cases, Raloxifene

Primary outcome

Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis)
Time frame: Exposure to study drug at least 720 days before disease onset
To determine the use of study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene) among female participants with esophageal cancer (cases) and a comparison subcohort, a case-cohort analysis was performed using women meeting criteria from the General Practice Research Database (GPRD, United Kingdom). Exposure to osteoporosis drugs administered 720 days before cancer onset was determined in cases and compared to contemporaneous assessments in a comparison subcohort matched by year of birth and membership in the GPRD on the case's onset date. Cases were confirmed and case onset dates determined by electronic algorithm (based on electronic medical record data) or by medical record review.
Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis)
Time frame: Up to approximately 7.3 years of follow-up
To assess the relative risk of esophageal cancer associated with osteoporosis study drugs (alendronate, etidronate, ibandronate, risedronate, and raloxifene), initiators of osteoporosis drugs and non-initiators (comparators, women sharing match criteria with the initiator) entered an inception cohort for every three-month period, beginning in the first quarter of 1996. Assignment to study drug exposure group remained fixed from the start of follow-up, analogous to an intent-to-treat analysis. The risk of esophageal cancer among initiators of study drug compared to non-initiators of study drug was estimated through calculation of a hazard ratio. For calculation of 721+ day hazard ratios, only esophageal cancer cases occurring at least 721 days from initiation of study drug were used. For calculation of 1441+ day hazard ratios, only esophageal cancer cases occurring at least 1441 days from initiation of study drug were used.

Results and safety

Results posted to the registry on 1 May 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Overall Study Population	684,815	684,815

Primary outcome: Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis)

Time frame: Exposure to study drug at least 720 days before disease onset. Number. Unit: Percentage of participants

Measure	Esophageal Cancer Cohort n = 929	Comparison Sample (Case Cohort) n = 338911
Alendronate	4.6	2.7
Etidronate	3.7	2.1
Ibandronate	0.3	0.03
Risedronate	2.6	0.9
Raloxifene	0.3	0.4

Esophageal Cancer Cohort vs Comparison Sample (Case Cohort): Hazard Ratio (HR): 1.1 (95% CI 0.7 to 1.5), Logistic Regression Model
Esophageal Cancer Cohort vs Comparison Sample (Case Cohort): Hazard Ratio (HR): 1.3 (95% CI 0.9 to 2.0), Logistic Regression Model
Esophageal Cancer Cohort vs Comparison Sample (Case Cohort): Hazard Ratio (HR): 4.9 (95% CI 1.4 to 16.7), Logistic Regression Model

Population analysed: Case-Cohort analysis population came from the Overall Study Population and comprised 929 women with esophageal cancer (cases) and a Comparison Sample of 338,911 matched control women. Participants may have been exposed to more than one study drug. Also, one comparator may have been used for multiple study drugs.

Primary outcome: Number of Cases of Esophageal Cancer Per 100,000 Woman-Years (Intent-to-Treat Analysis)

Time frame: Up to approximately 7.3 years of follow-up. Number. Unit: Number of cases per 100,0000 woman-years

Measure	Comparators n = 300610	Alendronate n = 48377	Etidronate n = 7851	Ibandronate n = 3941	Risendronate n = 15655	Raloxifene n = 2806
Value	32 (0.5 to 1.6)	32 (0.6 to 2.0)	42 (NA to NA)	46 (0.4 to 2.5)	47 (0.2 to 3.9)	29

Comparators vs Alendronate: Hazard Ratio (HR): 1.0 (95% CI 0.7 to 1.3), Proportional Hazards Regression Model
Comparators vs Etidronate: Hazard Ratio (HR): 1.3 (95% CI 0.8 to 2.0), Proportional Hazards Regression Model
Comparators vs Ibandronate: Hazard Ratio (HR): 1.3 (95% CI 0.5 to 3.4), Proportional Hazards Regression Model

Population analysed: Inception Cohort came from the Overall Study Population beginning treatment with an osteoporosis study drug (initiators, 78,630 women) and 300,610 matched control women, who did not receive study drug (noninitiators). Participants may have been exposed to more than one study drug. Also, one comparator may have been used for multiple study drugs.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Overall Study Population	0 of 0	0 of 0	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
EUPAS Register (EUPAS17909)Link provided by the sponsor.

Related trials for Esophageal Cancer

RecruitingPhase 2
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Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2/3
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Recruiting
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RecruitingObservational study
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RecruitingPhase 1/2
Beamion BCGC-1: A Study to Find a Suitable Dose of Zongertinib Used Alone and in Combination With Other Treatments to Test Whether it Helps People With Different Types of HER2+ Cancer That Has Spread
Metastatic Breast Cancer, Metastatic Gastric Adenocarcinoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Alec Walker, MD, DrPH study director

World Health Information Science Consultants, LLC

Questions about this trial

What is this clinical trial studying?

An observational study of Esophageal Cancer and Squamous Cell Carcinoma, run by Organon and Co.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 May 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Exposure to Study Drugs (Case-Cohort Analysis) (time frame: Exposure to study drug at least 720 days before disease onset). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01077817.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2022; AzTrials last refreshed its copy on 8 Nov 2026.