Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05797168
Registration number
NCT05797168
Ethics application status
Date submitted
21/02/2023
Date registered
4/04/2023
Date last updated
1/05/2024
Titles & IDs
Public title
Phase I/IIa Study for AZD5335 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors
Query!
Scientific title
FONTANA: A Modular Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Ascending Doses of AZD5335 Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors.
Query!
Secondary ID [1]
0
0
D8990C00001
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
FONTANA
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer
0
0
Query!
Lung Adenocarcinoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Ovarian and primary peritoneal
Query!
Cancer
0
0
0
0
Query!
Lung - Non small cell
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - AZD5335
Treatment: Drugs - AZD5305
Experimental: Module 1: AZD5335 Monotherapy - AZD5335 Monotherapy
Experimental: Module 2: AZD5335 + AZD5305 - AZD5335 + AZD5305
Treatment: Drugs: AZD5335
IV Antibody-drug conjugate
Treatment: Drugs: AZD5305
Oral PARP inhibitor
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Number of participants with adverse events/serious adverse events
Query!
Assessment method [1]
0
0
Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination.
Query!
Timepoint [1]
0
0
From time of Informed Consent to 30 days post last dose.
Query!
Primary outcome [2]
0
0
The number of participants with dose limiting toxicity(DLT), as defined in the protocol
Query!
Assessment method [2]
0
0
A DLT is defined as any = Grade 3 treatment-emergent AE that occurs during the DLT evaluation period, not attributable to the underlying disease or extraneous causes (as defined in the protocol)
Query!
Timepoint [2]
0
0
From the first dose of AZD5335 on Cycle 1 Day 1 up to and including the planned end of Cycle 1( At the end of 21 days if every 3 week dosing is tested or 28 days if every 4 weeks dosing is explored)
Query!
Secondary outcome [1]
0
0
Objective Response Rate (ORR)
Query!
Assessment method [1]
0
0
The percentage of participants with a confirmed CR or PR according to RECIST v1.1 criteria.
Query!
Timepoint [1]
0
0
From time of Informed Consent to progressive disease or withdrawal of consent.(approx 2 years)
Query!
Secondary outcome [2]
0
0
Duration of Response (DoR)
Query!
Assessment method [2]
0
0
The time from the date of first response until date of disease progression or death in the absence of disease progression.
Query!
Timepoint [2]
0
0
From the first documented response to confirmed progression or death in the absence of disease progression.(approx 2 years)
Query!
Secondary outcome [3]
0
0
Disease Control Rate (DCR)
Query!
Assessment method [3]
0
0
The percentage of participants who have a best objective response of confirmed CR or PR or who have SD for at least 15 weeks after start of treatment (to allow for an early assessment within the assessment window).
Query!
Timepoint [3]
0
0
From time of Informed Consent until progression.(approx 15 weeks)
Query!
Secondary outcome [4]
0
0
Progression free Survival (PFS)
Query!
Assessment method [4]
0
0
Progression-free survival is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from assigned therapy or receives another anti-cancer therapy prior to progression. Participants who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST v1.1 assessment
Query!
Timepoint [4]
0
0
From time of first dose of AZD5335 or AZD5305 until the date of objective disease progression or death (by any cause in the absence of progression).(approx 2 years)
Query!
Secondary outcome [5]
0
0
Overall Survival (OS)
Query!
Assessment method [5]
0
0
The time until death due to any cause.
Query!
Timepoint [5]
0
0
From time of first dose of AZD5335 or AZD5305 until death due to any cause.(approx 2 years)
Query!
Secondary outcome [6]
0
0
Module 1: Pharmacokinetics of AZD5335: Area Under the concentration-time curve(AUC)
Query!
Assessment method [6]
0
0
Area under the plasma concentration-time curve
Query!
Timepoint [6]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335(approximately 12 weeks)
Query!
Secondary outcome [7]
0
0
Module 1: Pharmacokinetics of AZD5335: Maximum plasma concentration of the study drug (Cmax)
Query!
Assessment method [7]
0
0
Maximum observed plasma concentration of the study drug
Query!
Timepoint [7]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335 (approximately 12 weeks)
Query!
Secondary outcome [8]
0
0
Module 1: Pharmacokinetics of AZD5335: Time to maximum plasma concentration of the study drug (T-max)
Query!
Assessment method [8]
0
0
Time to maximum observed plasma concentration of the study drug
Query!
Timepoint [8]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335 (approximately 12 weeks)
Query!
Secondary outcome [9]
0
0
Module 1: Pharmacokinetics of AZD5335: Clearance
Query!
Assessment method [9]
0
0
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
Query!
Timepoint [9]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335 (approximately 12 weeks)
Query!
Secondary outcome [10]
0
0
Module 1: Pharmacokinetics of AZD5335: Terminal elimination half-life (t 1/2)
Query!
Assessment method [10]
0
0
Terminal elimination half life.
Query!
Timepoint [10]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335 (approximately 12 weeks)
Query!
Secondary outcome [11]
0
0
Pharmacodynamics of AZD5335
Query!
Assessment method [11]
0
0
The pharmacodynamics of AZD5335 by assessing changes in peripheral blood including, but not limited to cytokines, CA-125 and ctDNA.
Query!
Timepoint [11]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335(approx 2 years)
Query!
Secondary outcome [12]
0
0
Immunogenicity of AZD5335
Query!
Assessment method [12]
0
0
The number and percentage of participants who develop ADAs.
Query!
Timepoint [12]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5535.(approx 2 years)
Query!
Secondary outcome [13]
0
0
Module 1: To investigate baseline and on treatment changes in target expression.
Query!
Assessment method [13]
0
0
The clinical activity by baseline and on-treatment changes in tumor target expression.
Query!
Timepoint [13]
0
0
Baseline and predicted intervals throughout the administration of AZD5335(approx 2 years)
Query!
Secondary outcome [14]
0
0
Module 2: Pharmacokinetics of AZD5335 and AZD5305 when given in combination.
Query!
Assessment method [14]
0
0
The plasma concentrations of AZD5335, total antibody, and total unconjugated warhead.
Query!
Timepoint [14]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335 and AZD5305.(approx 12 weeks)
Query!
Secondary outcome [15]
0
0
Module 2: Area Under the concentration-time curve (AUC)
Query!
Assessment method [15]
0
0
Area under the plasma concentration-time curve
Query!
Timepoint [15]
0
0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Query!
Secondary outcome [16]
0
0
Module 2: Maximum plasma concentration of the study drug (Cmax)
Query!
Assessment method [16]
0
0
Maximum observed plasma concentration of the study drug
Query!
Timepoint [16]
0
0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Query!
Secondary outcome [17]
0
0
Module 2: Time to maximum plasma concentration of the study drug (T-max)
Query!
Assessment method [17]
0
0
Time to maximum observed plasma concentration of the study drug
Query!
Timepoint [17]
0
0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Query!
Secondary outcome [18]
0
0
Module 2: Clearance
Query!
Assessment method [18]
0
0
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
Query!
Timepoint [18]
0
0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Query!
Secondary outcome [19]
0
0
Module 2: Terminal elimination half-life (t 1/2)
Query!
Assessment method [19]
0
0
Terminal elimination half life.
Query!
Timepoint [19]
0
0
From the first dose of study intervention, at predefined intervals throughout the administration of AZD5335 (approximately 12 weeks)
Query!
Eligibility
Key inclusion criteria
Core
- Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form and in this
protocol.
- Provision of signed and dated written Optional Genetic Research Information informed
consent prior to collection of samples for optional genetic research that supports
Genomic Initiative. Participants who do not provide informed consent for Optional
Genetic Research may still be enrolled in the study.
- Consent to provide adequate baseline tumor sample, as applicable per module-specific
criteria.
- Participant must be = 18 years at the time of signing the informed consent.
- Willing to provide archival or baseline tumor sample.
- For participants who have previously received targeted therapies such as ADCs, a fresh
baseline biopsy will be required.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Participants with advanced solid tumors must have received prior adequate therapy in
accordance with local practice for their tumor type and stage of disease, or, in the
opinion of the Investigator, a clinical trial is the best option for the next
treatment based on response and/or tolerability to prior therapy. Participants with
contraindications or who refuse therapy in accordance with local practice may also be
considered provided that it is documented that he/she was informed about all
therapeutic options.
- Participants must have measurable disease per RECIST v1.1,
1. A previously irradiated lesion can be considered a target lesion if the lesion is
progressing and well defined.
2. For participants who undergo biopsies at screening and/or on treatment, it is
preferred though not required, that the biopsied lesion, be distinct from any
target lesion used in the RECIST v1.1 evaluation.
- Life expectancy = 12 weeks.
- Adequate organ and marrow function.
- Contraceptive use by men or women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
(a) Male participants: (i) Non-sterilized male participants who are sexually active
with a female partner of childbearing potential must use a male condom (plus
spermicide, if available) post-screening through 5 half-lives (45 days) plus 6 months
(approximately 7.5 months) following the last dose of study intervention. It is
strongly recommended for the female partner of a male participant to also use a highly
effective method of contraception throughout this period. In addition, male
participants must refrain from sperm donation while on study and for 5 half lives (45
days) plus 6 months (~7.5 months) following the last dose of study intervention.
(b) Female participants: (i) Females of childbearing potential must have a negative
urine or serum pregnancy test within 72 hours prior to receiving the first dose of
study intervention and a negative urine or serum pregnancy test prior to starting
their next cycle of treatment. If the urine test is positive or cannot be confirmed as
negative, a serum pregnancy test will be required.
Female participants of childbearing potential who are sexually active with a non-sterilized
male partner must agree to use one highly effective method of birth control (defined as one
that can achieve a failure rate of less than 1% per year when used consistently and
correctly), from enrolment throughout the study and for 5 half-lives (45 days) plus 6
months (In total, 7.5 months) following the last dose of study intervention. It is strongly
recommended for the male partner of a female participants to also use male condom (plus
spermicide, if available) throughout this period. Cessation of contraception after this
point should be discussed with a responsible physician. In addition, female participants
must refrain from egg donation while on study and for 5 half-lives (45 days) plus 6 months
(~7.5 months) following the last dose of study intervention.
Core
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
130
Years
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
- Patients with spinal cord compression or a history of leptomeningeal carcinomatosis.
- Patients with brain metastases unless, asymptomatic, stable, and not requiring
continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at
least 4 weeks prior to first dose of study intervention.
- Treatment with any of the protocol defined medications, without adequate washout
periods or time before the first dose of study intervention.
- Unresolved toxicities of Grade = 2 (National Cancer Institute [NCI] Common Terminology
Criteria for Adverse Events [CTCAE] v5.0) from prior therapy (excluding vitiligo,
alopecia, and endocrine disorders that are controlled with replacement hormone
therapy). Participants with stable = Grade 2 neuropathy are eligible.
- Active infection, including tuberculosis and infections with hepatitis B virus (HBV;
verified by known positive hepatitis B surface antigen [HBsAg] result), hepatitis C
virus (HCV) or known HIV infection that is not well controlled. All of the following
criteria are required to define an HIV infection that is well controlled: undetectable
viral RNA, CD4+ count = 350/mm3, no history of acquired immune deficiency
syndrome-defining opportunistic infection within the past 12 months, and stable for at
least 4 weeks on the same anti-HIV medications (meaning there are no expected further
changes in that time to the number or type of antiretroviral drugs in the regimen).
Patients with a past or resolved HBV/HCV infection are eligible if:
(a) Negative for HBsAg and positive for anti-HBc or (b) Are HBsAg + with chronic HBV
infection (lasting 6 months or longer) and meet conditions i-iii below: (i) HBV DNA viral
load <100 IU/mL. (ii) Have normal transaminase values, or, if liver metastases are present,
abnormal transaminases, with a result of AST/ALT <3 × ULN, which are not attributable to
HBV infection.
(iii) Start or maintain antiviral treatment if clinically indicated as per the Investigator
or as per local guideline.
Note for Japan: Japanese patients with positive anti-HBs/anti-HBc and negative HBsAg will
be assessed following local guidelines.
(c) Participants testing positive for HCV antibody are eligible only if the polymerase
chain reaction test result is negative for HCV RNA.
- Patient has ILD/pneumonitis or has a history of (non-infectious) ILD/pneumonitis that
required oral or IV steroids or supplemental oxygen, or where suspected
ILD/pneumonitis cannot be ruled out by imaging at screening.
- Patients with a history of radiation pneumonitis which has clinically and
radiologically resolved and not requiring treatment with steroids may be
eligible.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease for at
least 2 years prior to screening of study intervention and with low potential
risk for recurrence.
- Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of
disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Localized non-invasive primary disease under surveillance.
- Patients with any of the following cardiac criteria:
- History of arrhythmia (such as multifocal premature ventricular contractions,
bigeminy, trigeminy, and ventricular tachycardia), which is symptomatic or
requires treatment (NCI CTCAE v5.0 Grade 3); symptomatic or uncontrolled atrial
fibrillation despite treatment, or asymptomatic sustained ventricular
tachycardia.
- NOTE: significant abnormalities in serum electrolytes that can increase the
risk of arrhythmic events (ie, sodium, potassium, calcium, and magnesium)
should be corrected before starting the study intervention.
- Uncontrolled hypertension.
- Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris,
coronary intervention procedure with percutaneous coronary intervention, or
coronary artery bypass grafting within 6 months of screening.
- History of brain perfusion problems (eg, carotid stenosis) or stroke, or
transient ischemic attack in the last 6 months prior to screening.
- Symptomatic heart failure (as defined by New York Heart Association class = 2).
- Prior or current cardiomyopathy.
- Severe valvular heart disease.
- Mean resting QTcF > 470 msec obtained from triplicate ECGs and averaged, recorded
within 5 minutes.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, congenital long QT syndrome, family history of long
QT syndrome or unexplained sudden death under 40 years of age.
- Uncontrolled intercurrent illness within 12 months prior to screening, including but
not limited to serious chronic GI conditions associated with diarrhea, or psychiatric
illness/social situations that would limit compliance with study requirements and
activities, substantially increase risk of incurring AEs or compromise the ability of
the participant to give written informed consent.
- Substance abuse or any other medical conditions that would increase the safety risk to
the participant or interfere with participation of the participant or evaluation of
the clinical study in the opinion of the Investigator.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study
intervention. Note: Participants, if enrolled, should not receive live vaccine whilst
receiving study intervention and up to 30 days after the last dose of study
intervention. Participants can receive Coronavirus (COVID)-19 vaccines, at the
discretion of the Investigator, following a benefit/risk evaluation for the individual
participant and in accordance with local rules and regulations and vaccination
guidelines. Note: If a COVID-19 vaccine is administered it should be done > 72 hours
prior to study intervention initiation or after completion of the DLT period.
- For women only - currently pregnant (confirmed with positive pregnancy test),
lactating, breastfeeding, or intend to become pregnant during the study period.
- Concurrent enrolment in another clinical study, unless it is an observational (non
interventional) clinical study or during the follow-up period of an interventional
study.
- Patients with a known hypersensitivity to study intervention or any of the excipients
of the product.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site).
- Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions and
requirements.
- Previous enrolment in the present study. **Other module specific criteria may apply
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
N/A
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Other
Query!
Other design features
Query!
Phase
Phase 1/Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Recruiting
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
5/06/2023
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
1/11/2027
Query!
Actual
Query!
Sample size
Target
150
Query!
Accrual to date
Query!
Final
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Research Site - Liverpool
Query!
Recruitment hospital [2]
0
0
Research Site - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
2170 - Liverpool
Query!
Recruitment postcode(s) [2]
0
0
3000 - Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
California
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Colorado
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Kentucky
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Massachusetts
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Ohio
Query!
Country [6]
0
0
United States of America
Query!
State/province [6]
0
0
Oregon
Query!
Country [7]
0
0
United States of America
Query!
State/province [7]
0
0
Rhode Island
Query!
Country [8]
0
0
United States of America
Query!
State/province [8]
0
0
Texas
Query!
Country [9]
0
0
Canada
Query!
State/province [9]
0
0
Alberta
Query!
Country [10]
0
0
Canada
Query!
State/province [10]
0
0
Ontario
Query!
Country [11]
0
0
Canada
Query!
State/province [11]
0
0
Quebec
Query!
Country [12]
0
0
China
Query!
State/province [12]
0
0
Chengdu
Query!
Country [13]
0
0
China
Query!
State/province [13]
0
0
Chongqing
Query!
Country [14]
0
0
China
Query!
State/province [14]
0
0
Jinan
Query!
Country [15]
0
0
China
Query!
State/province [15]
0
0
Xi'an
Query!
Country [16]
0
0
China
Query!
State/province [16]
0
0
Zhengzhou
Query!
Country [17]
0
0
Israel
Query!
State/province [17]
0
0
Haifa
Query!
Country [18]
0
0
Israel
Query!
State/province [18]
0
0
Ramat Gan
Query!
Country [19]
0
0
Japan
Query!
State/province [19]
0
0
Kashiwa
Query!
Country [20]
0
0
Japan
Query!
State/province [20]
0
0
Tokyo
Query!
Country [21]
0
0
Spain
Query!
State/province [21]
0
0
Barcelona
Query!
Country [22]
0
0
Spain
Query!
State/province [22]
0
0
Madrid
Query!
Country [23]
0
0
Spain
Query!
State/province [23]
0
0
Málaga
Query!
Country [24]
0
0
Taiwan
Query!
State/province [24]
0
0
Taichung
Query!
Country [25]
0
0
Taiwan
Query!
State/province [25]
0
0
Tainan City
Query!
Country [26]
0
0
Taiwan
Query!
State/province [26]
0
0
Taipei
Query!
Country [27]
0
0
United Kingdom
Query!
State/province [27]
0
0
Cambridge
Query!
Country [28]
0
0
United Kingdom
Query!
State/province [28]
0
0
Glasgow, Scotland
Query!
Country [29]
0
0
United Kingdom
Query!
State/province [29]
0
0
London
Query!
Country [30]
0
0
United Kingdom
Query!
State/province [30]
0
0
Sutton
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
AstraZeneca
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
This research is designed to determine if experimental treatment with Antibody-drug
conjugate, AZD5335, alone, or in combination with anti-cancer agents is safe, tolerable, and
has anti-cancer activity in patients with advanced tumors
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT05797168
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Funda Meric-Bernstam, MD
Query!
Address
0
0
UT MD Anderson Cancer Center
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
AstraZeneca Clinical Study Information Center
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
1-877-240-9479
Query!
Fax
0
0
Query!
Email
0
0
[email protected]
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05797168
Download to PDF