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
Both
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