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
- Conditions
- Ovarian Cancer
- Registration Number
- JPRN-jRCT2031230175
- Lead Sponsor
- Hibi Kazushige
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Female
- Target Recruitment
- 361
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 or more 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.
- 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 following, without adequate washout periods or time before the first dose of study intervention.
- Unresolved toxicities of Grade 2 or more (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 or less 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 or more, 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 x 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.
NO
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - Number of participants with adverse events/serious adverse events [ Time Frame: From time of Informed Consent to 30 days post last dose. ]<br>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.<br><br>- The number of participants with dose limiting toxicity(DLT), as defined in the protocol [ Time Frame: 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) ]<br>ADLT is defined as any or more 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)
- Secondary Outcome Measures
Name Time Method