Condition category
Cancer
Date applied
12/09/2016
Date assigned
16/09/2016
Last edited
24/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information

Type

Public

Primary contact

Ms Anna Morris

ORCID ID

Contact details

CRUK CTU
Level 0 Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Type

Scientific

Additional contact

Ms Anna Morris

ORCID ID

Contact details

CRUK CTU
Level 0 Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Additional identifiers

EudraCT number

2015-003249-25

ClinicalTrials.gov number

Protocol/serial number

ATLANTIS_2015

Study information

Scientific title

An adaptive multi-arm phase II trial of maintenance targeted therapy after chemotherapy in metastatic urothelial cancer

Acronym

ATLANTIS

Study hypothesis

The trial hypothesis is that the addition biomarker targeted novel agents used as maintenance therapy after chemotherapy will improve clinical efficacy in patients with metastatic urothelial cancer.

Ethics approval

Not provided at time of registration

Study design

Multi-centre randomised phase II trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Metastatic urothelial cancer

Intervention

Multiple novel agents will be tested in parallel and patients will enter into particular ATLANTIS component subgroup studies dependent on their biomarker profile. The control arm will be placebo-controlled and double blind. The initial subgroup will investigate cabozantinib versus matched placebo at 40mg PO once daily.

Cabozantinib drug subgroup:
Patients will receive continuous daily dosing (days 1-28 of a 28 day cycle) until progression or unacceptable toxicity.

1. Control arm: Matched placebo 40mg once daily in the fasted state i.e. no food for at least 2 hours before through to 1 hour after taking.
2. Experimental arm: Cabozantinib 40mg once daily in the fasted state i.e. no food for at least 2 hours before through to 1 hour after taking.

Dose reductions are recommended for events that, if persistent, could become serious or intolerable. The dose may be reduced (to 20mg of cabozantinib) due to treatment related toxicity. This should be clinically driven. Patients with grade 3 or 4 toxicity (as per CTCAE version 4.03) should be considered for a dose reduction, following recovery to grade 1 or baseline.

Patients will continue to receive trial drug/placebo until progression, unacceptable toxicity, start of further systemic anticancer therapy, withdrawal of consent or the investigator decides it is not in the best interest of the patient to continue. Patients will be followed up for overall survival and further systemic anti-cancer treatments after progression has occurred. Data will be collected until 8 months after the last patient has been enrolled.

Intervention type

Drug

Phase

Phase II

Drug names

Cabozantinib

Primary outcome measures

Progression free survival- RECIST 1.1 tumour measurements, assessed 12 weekly during trial treatment. PFS is time from randomisation until progression or death, whichever occurs first

Secondary outcome measures

1. Overall survival - follow up by local investigator
2. Safety and tolerability - CTCAE assessment every 4 weeks whilst on study treatment
3. Response rate- RECIST 1.1 tumour measurements, assessed 12 weekly during trial treatment. Best response recorded from the start of treatment until disease progression
4. Maximum reduction in the size of measurable lesions - RECIST 1.1 tumour measurements, assessed 12 weekly during trial treatment. Maximum reduction recorded from the start of treatment until disease progression

Overall trial start date

31/10/2016

Overall trial end date

01/07/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Previously diagnosed stage IV urothelial cancer (UC) (T4b, Nany, Many; Tany, N 1-3, M0; Tany, Nany, M1) see Appendix II)
2. Histologically confirmed urothelial cancer. This includes cancers of the urinary bladder, ureter, renal pelvis or urethra with transitional and/or squamous histology. A component of either or both of these histologies is adequate for entry
3. Able to commence the trial treatment within 10 weeks of completing chemotherapy
4. Adequate tissue for biomarker testing. Testing will occur centrally
5. Patients must have received between 4 and 8 cycles of first line chemotherapy for metastatic/advanced UC to be eligible **. Previous adjuvant or neoadjuvant chemotherapy does not count as a line of therapy
6. Adequate organ function as defined in the relevant subgroup specific appendix
7. ECOG performance status 0-2
8. Age ≥ 16 years
9. Female patients of childbearing potential must agree to comply with effective contraceptive measures, has been using adequate contraception since the last menses, will use adequate contraception during the trial, and has a negative pregnancy test within one week of trial entry.
10. Male patients with partners of child-bearing potential must agree to take measures not to father children by using one form of highly effective contraception, effective at the first administration of IMP and throughout the trial
11. Written informed consent prior to admission to this trial
12. Meets all inclusion criteria for the relevant component subgroup listed in the appendices
**Standard chemotherapy consists of any widely accepted regimen. Patients who have had delays in treatment or dose reductions should not be excluded, providing they received at least 4 cycles of treatment.

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

140

Participant exclusion criteria

1. Progression during first-line chemotherapy for metastatic disease. This should be based on a radiological comparison between the pre-chemotherapy CT and end of treatment CT (local review). Patients may be permitted to enter the trial if their end of chemotherapy scan shows response or stable disease (local assessment using RECIST 1.1) when compared to their latest pre-chemotherapy scan, even if there is progression when compared to a nadir scan performed during chemotherapy. These patients should be discussed with the trial team
2. In the opinion of the Investigator requires second line chemotherapy
3. More than one line of chemotherapy for metastatic or locally advanced disease (where the regimen is changed during first-line treatment without evidence of progression (for example the patient changes from cisplatin to carboplatin due to toxicity) this will constitute a single line of chemotherapy). Prior adjuvant / neoadjuvant chemotherapy is permitted in addition
4. Patients receiving radical/curative surgery or radiotherapy at the end of first line treatment (palliative radiotherapy is allowed but must be > 2 weeks prior to trial entry)
5. Patients receiving less than 4 or more than 8 cycles of chemotherapy before randomisation and initiation of trial intervention (excluding any chemotherapy given as neo-adjuvant / adjuvant)
6. Treatment with any other investigational agent within 28 days prior to first dose of trial medication within ATLANTIS
7. Less than 3 or more than 10 weeks since the last infusion of first-line chemotherapy for advanced/metastatic UC at time of initiation of trial interventions
8. History of another malignancy in the last 2 years (other than treated squamous/basal cell skin cancer, treated early stage cervical cancer or treated / biochemically stable, organ confined prostate cancer not requiring on-going androgen deprivation therapy)
9. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder)
10. Positive pregnancy test for females
11. Inadequate organ function as defined in drug-specific appendices
12. Ongoing therapy with prohibited medication which cannot be discontinued prior to starting trial specific intervention (as defined in drug-specific appendices)
13. Major surgery or any radiotherapy within 3 weeks prior to trial entry (palliative radiotherapy within >2 weeks prior to trial entry is permitted)
14. Significant comorbidity or serious intercurrent medical or psychiatric illness, including serious active infection which, in the opinion of the investigator would make it inappropriate for the patient to enter the trial
15. Women who are breast feeding
16. Meets any of the exclusion criteria listed in the relevant component subgroup specific appendix

Recruitment start date

01/11/2016

Recruitment end date

30/11/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Rd
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Barts and the London NHS Trust
London
EC1A 7BE
United Kingdom

Trial participating centre

Guy's and St Thomas' Hospital
London
SE1 7EH
United Kingdom

Trial participating centre

Southampton General Hospital
Southampton
SO16 6YD
United Kingdom

Trial participating centre

The Clatterbridge Cancer Centre
Clatterbridge Health Park Clatterbridge Rd
Wirral
CH63 4JY
United Kingdom

Trial participating centre

Royal Lancaster Infirmary
Lancaster
LA1 4RP
United Kingdom

Trial participating centre

Velindre NHS Trust
2 Charnwood Court Heol Billingsley Parc Nantgarw
Cardiff
CF14 2TL
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde

Sponsor details

Clinical Research and Development
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Organisation

University of Glasgow

Sponsor details

Clinical Research and Development
West Glasgow Ambulatory Care Hospital
Dalnair Street
Glasgow
G3 8SW
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Not defined

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Exelixis Inc

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The ATLANTIS TMG is responsible for approving the content and dissemination of all publications, abstracts and presentations arising from the trial and for assuring the confidentiality and integrity of the trial.

Intention to publish date

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/11/2016: Internal review.