Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000697482
Ethics application status
Approved
Date submitted
22/05/2025
Date registered
1/07/2025
Date last updated
1/07/2025
Date data sharing statement initially provided
1/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Doxycycline Use in Lung CancEr (DULCE)
Scientific title
A parallel-group, 2-arm, Phase 2, multisite, stratified, double-blind, randomised, study to investigate the safety and effectiveness of doxycycline or placebo in conjunction with standard of care in adults with metastatic adenocarcinoma of the lung undergoing targeted anti-cancer therapy.
Secondary ID [1] 314330 0
Nil known
Universal Trial Number (UTN)
Trial acronym
DULCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung cancer 337285 0
Condition category
Condition code
Cancer 333684 333684 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Doxycycline 100 mg tablet, 100 mg oral twice a day on the first day followed by 100 mg oral once a day for the next 27 days. Treatment period is 28 days total. Participants will receive doxycycline alongside their standard of care lung cancer treatment which will be determined prior to commencing on the study by their treating oncologist according to the local cancer treatment protocols and must include targeted therapy. Adherence to the study intervention will be monitored through the completion of weekly patient diaries to record doses taken as well as final accountability of tablets returned.
Intervention code [1] 330941 0
Treatment: Drugs
Comparator / control treatment
Placebo tablet, 1 tablet oral twice a day on the first day followed by 1 tablet once a day for the next 27 days. Treatment period is 28 days total.. Participants will receive placebo alongside their standard of care lung cancer treatment which will be determined prior to commencing on the study by their treating oncologist according to the local cancer treatment protocols and must include targeted therapy. Adherence to the intervention will be monitored through the completion of weekly patient diary to record doses taken as well as final accountability of tablets returned.
Control group
Placebo

Outcomes
Primary outcome [1] 341274 0
To determine the efficacy of doxycycline or placebo in conjunction with standard of care in participants with adenocarcinoma
Timepoint [1] 341274 0
12 months after randomisation (+/- 28 days)
Secondary outcome [1] 447000 0
To determine the effects of doxycycline or placebo in conjunction with standard of care on the oral microbiome
Timepoint [1] 447000 0
Day 1, day 28 (+/- 2 days), 3 months after randomisation
Secondary outcome [2] 446998 0
To describe medical resource utilisation of participants treated with doxycycline or placebo in conjunction with standard of care
Timepoint [2] 446998 0
Day 28 (+/- 2 days), 3 months and then 12 months after randomisation (+/- 28 days)
Secondary outcome [3] 446996 0
To determine progression free survival of participants treated with doxycycline or placebo in conjunction with standard of care
Timepoint [3] 446996 0
Day 35 (+/- 3 days), 3 months and then 12 months after randomisation (+/- 28 days)
Secondary outcome [4] 446997 0
To determine response to treatment for participants treated with doxycycline or placebo in conjunction with standard of care
Timepoint [4] 446997 0
Day 28 (+/- 2 days), 3 months and then 12 months after randomisation (+/- 28 days)
Secondary outcome [5] 448857 0
To determine the effects of doxycycline or placebo in conjunction with standard of care on the gut microbiome
Timepoint [5] 448857 0
Day 1, day 28 (+/- 2 days), 3 months after randomisation
Secondary outcome [6] 446999 0
To describe the safety and tolerability of doxycycline or placebo in conjunction with standard of care
Timepoint [6] 446999 0
Day 1, day 28 (+/- 2 days), 3 months and then 12 months after randomisation (+/- 28 days)

Eligibility
Key inclusion criteria
Signed informed consent
Participant must be 18 years of age or over, at the time of signing the informed consent
Participants who have a diagnosis of adenocarcinoma of the lung.
The adenocarcinoma is metastatic.
The participant has commenced targeted therapy (± chemotherapy) within the previous 7 to 35 days and is continuing on that therapy at the time of commencement of the trial medication.
Willing to use (or the participant’s partner is willing to use) contraception as per local regulations for methods of contraception in people undergoing targeted anticancer therapies.
A woman of childbearing potential must be willing to undergo a highly sensitive pregnancy test urine or serum (as required by local regulations) within 24 hours before the first dose of study intervention
Able to complete the patient diary
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant or breastfeeding
Have rapidly progressing disease during first line therapy
Planned or current targeted treatment with immunotherapy.
Hypersensitivity to, or inability to tolerate, doxycycline, any of the excipients of doxycycline or to any other tetracycline.
Concomitant treatment with oral retinoids, including isotretinoin, etretinate and Vitamin A within the last 6 months.
Regular concomitant treatment with calcium, magnesium or aluminium supplements; including antacids.
Concomitant medications containing bismuth salts, or iron.
Use of methoxyflurane within the last 48 hours.
Concomitant use of phenobarbital (phenobarbitone), carbamazepine, or rifampicin
Unable to swallow study medication.
Have ALT or AST greater than or equal to 3 times or bilirubin greater than or equal to 5 times the upper limit of normal (excluding those with Gilbert’s syndrome).
Severe renal impairment in the last 60 days (eGFR < 15 ml/min/1.73m2)
Any other condition, which in the investigator’s opinion should preclude the participant from inclusion in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be allocated centrally by the dispensing pharmacy. Investigational Medicinal Product will be labelled with: name, address and telephone number of the sponsor, investigator (the main contact for information on the product, clinical trial and emergency unblinding); the name/identifier and strength/potency (indicating “placebo/comparator or doxycycline 100 mg”); pharmaceutical dosage form, route of administration, and quantity of dosage units; the batch number; trial reference code; the trial subject identification number/treatment number; directions for use; “For clinical trial use only”; storage conditions; expiry date; and “keep out of reach of children”; in accordance with local regulatory guidelines
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer-generated randomisation schedule will be developed by the sponsor or their designee. Randomisation will be stratified by participant’s self-recall of any antibiotic exposure in the six months leading up to the commencement of targeted therapies. The strata will be:
Strata 1 – no antibiotic exposure recalled within the last 6 months
Strata 2 – antibiotic use in prior 6 months recalled
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The null hypothesis is that doxycycline is not different from placebo with respect to the composite endpoint.

The alternative hypothesis is that doxycycline is different from placebo with respect to the composite endpoint.The analysis and reporting will be conducted on all data from all participants at the time the study ends (intention-to-treat).

The primary objective is to demonstrate a significant win ratio >1 following 28-days of treatment with doxycycline compared to placebo.

The primary endpoint is a hierarchical composite endpoint of the ‘loser’ working through each of these comparisons sequentially:
1. Death, (or the earlier time to death if both participants in that comparison die)
2. Response (or the earlier time to progression if response is the same for both participants in the comparison)
3. Toxicity (Grade 4 or greater, or first person to experience that toxicity if both participants in the comparison have the same level of toxicity)
4. Hospitalisation (and longer duration of hospitalisations if both participants in that comparison experience hospitalisations)
5. Delay to scheduled targeted therapy (or the earlier the event occurs for both participants in a comparison where both experience it)
A ‘tie’ occurs if there are no differences after the fifth comparison.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2025
Actual
Date of last participant enrolment
Anticipated
1/08/2026
Actual
Date of last data collection
Anticipated
1/08/2027
Actual
Sample size
Target
58
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT
Recruitment hospital [1] 27861 0
Wollongong Hospital - Wollongong
Recruitment hospital [2] 27863 0
Westmead Hospital - Westmead
Recruitment hospital [3] 27859 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [4] 27860 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [5] 27862 0
Alice Springs Hospital - Alice Springs
Recruitment postcode(s) [1] 44056 0
2500 - Wollongong
Recruitment postcode(s) [2] 44055 0
2050 - Camperdown
Recruitment postcode(s) [3] 44054 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 44058 0
2145 - Westmead
Recruitment postcode(s) [5] 44057 0
0870 - Alice Springs

Funding & Sponsors
Funding source category [1] 318848 0
Charities/Societies/Foundations
Name [1] 318848 0
Tour de Cure Pioneering Research Grant
Country [1] 318848 0
Australia
Funding source category [2] 318849 0
University
Name [2] 318849 0
University of Technology internal funds
Country [2] 318849 0
Australia
Primary sponsor type
University
Name
University of Technology Sydney
Address
Country
Australia
Secondary sponsor category [1] 321301 0
None
Name [1] 321301 0
Address [1] 321301 0
Country [1] 321301 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317465 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 317465 0
Ethics committee country [1] 317465 0
Australia
Date submitted for ethics approval [1] 317465 0
16/04/2025
Approval date [1] 317465 0
17/06/2025
Ethics approval number [1] 317465 0
2025/ETH00769

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 141126 0
Prof David Currow
Address 141126 0
University of Technology Sydney 15 Broadway Ultimo NSW 2007
Country 141126 0
Australia
Phone 141126 0
+61 0423 251 710
Fax 141126 0
Email 141126 0
[email protected]
Contact person for public queries
Name 141127 0
Charmain Strauss
Address 141127 0
University of Technology Sydney 15 Broadway Ultimo NSW 2007
Country 141127 0
Australia
Phone 141127 0
+61 0414190084
Fax 141127 0
Email 141127 0
[email protected]
Contact person for scientific queries
Name 141128 0
David Currow
Address 141128 0
University of Technology Sydney 15 Broadway Ultimo NSW 2007
Country 141128 0
Australia
Phone 141128 0
+61 0423 251 710
Fax 141128 0
Email 141128 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
• Studies exploring new research questions
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Data sharing request system: Health Data Australia (HeSANDA)

• Email of trial custodian, sponsor or committee: University of Technology Sydney (IMPAACT) (Email: [email protected])

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  [email protected]
Statistical analysis plan  [email protected]
Informed consent form  [email protected]
Ethical approval  [email protected]


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.