BAY 1895344 Plus Topoisomerase-1 (Top1) Inhibitors in Patients with Advanced Solid Tumors, Phase I Studies with Expansion Cohorts in Small Cell Lung Carcinoma (SCLC), Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) and Pancreatic Adenocarcinoma (PDA)

Overview

About this study

The purpose of this study is to test the safety and tolerability of a drug called BAY 1895344 in combination with irinotecan or topotecan at different doses. 

Irinotecan has already been approved by the FDA to treat pancreatic cancer while topotecan has already been approved by the FDA to treat small cell lung cancer.

Another purpose of the study is to check the level of the study drugs in your blood called pharmacokinetics or PK and to see if there are changes in levels of circulating tumor cells in your blood. To assess what effect the study drugs have on damaging the DNA of your cancer, pharmacodynamic or PD studies will be performed from the on-treatment tumor biopsies for patients in the expansion group.  In addition, another objective of the study is for future biobanking studies related to your tumor and blood samples such as a biomarker study.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- DOSE ESCALATION COHORTS: Patients must have a biopsy-proven solid tumor that is
metastatic or unresectable and has progressed on at least one line of standard therapy

- DOSE ESCALATION COHORTS: Patients must have a solid tumor for which irinotecan or
topotecan is considered standard of care

- DOSE EXPANSION COHORTS: Patients must have biopsy proven metastatic or unresectable
small cell lung cancer (SCLC), poorly differentiated neuroendocrine carcinoma (PD-NEC)
(any extrapulmonary neuroendocrine carcinoma with small cell or large cell histology)
or pancreatic adenocarcinoma (PDA) and have progressed on at least one line of
standard therapy

- DOSE EXPANSION COHORTS: Patients must have at least one measurable lesion outside of
the lesion to be biopsied

- Patients must be able to swallow pills

- Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of BAY 1895344 in combination with irinotecan or topotecan in patients < 18
years of age, children are excluded from this study

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

- Hemoglobin > 9 g/dL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin =< 2 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3 x institutional ULN

- Glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial

- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
load must be undetectable on suppressive therapy, if indicated

- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load

- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression.
Furthermore, these patients must be asymptomatic from previously treated brain
metastases (e.g. not on steroids for neurologic symptoms within 30 days of study
enrollment)

- Patients with a prior or concurrent malignancy whose natural history or treatment does
not have the potential to interfere with the safety or efficacy assessment of the
investigational regimen are eligible for this trial

- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better

- The effects of BAY 1895344 on the developing human fetus are unknown. For this reason
and because DNA-damage response inhibitors as well as other therapeutic agents used in
this trial are known to be teratogenic, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation and for 6
months after completion of BAY 1895344 administration. Should a woman become pregnant
or suspect she is pregnant while she or her partner is participating in this study,
she should inform her treating physician immediately. Men treated or enrolled on this
protocol must also agree to use adequate contraception prior to the study, for the
duration of study participation, and 6 months after completion of BAY 1895344
administration

- Patient must have the ability to understand and the willingness to sign a written
informed consent document. Participants with impaired decision-making capacity (IDMC)
who have a legally-authorized representative (LAR) and/or family member available will
also be eligible

Exclusion Criteria:

- Patients who have previously been treated with irinotecan will not be eligible to
participate in the irinotecan arm and patients who have previously been treated with
topotecan will not be eligible to participate in the topotecan arm. However, patients
who previously received irinotecan may be treated with topotecan (and vice versa)
should the other agent be considered a possible standard of care for their disease.
Patients who have previously been treated with BAY 1895344 will be excluded from the
study

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study

- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > grade 1) with the exception of alopecia and
endocrinopathies from prior immunotherapy

- Patients who are receiving any other investigational agents

- The investigator(s) must state a medical or scientific reason if patients who have
brain metastases will be excluded from the study

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to BAY 1895344 or other agents used in study

- Patients receiving any medications or substances that are substrates of CYP3A4 with a
narrow therapeutic window, or strong inhibitors/inducers of CYP3A4 are ineligible, if
they cannot be transferred to alternative medication. Because the lists of these
agents are constantly changing, it is important to regularly consult a
frequently-updated medical reference. As part of the enrollment/informed consent
procedures, the patient will be counseled on the risk of interactions with other
agents, and what to do if new medications need to be prescribed or if the patient is
considering a new over-the-counter medicine or herbal product

- Patients with uncontrolled intercurrent illness

- Patients with psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because BAY 1895344 is agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with BAY 1895344, breastfeeding should be discontinued if the mother is treated
with BAY 1895344. These potential risks may also apply to other agents used in this
study

- Patients with an uncontrolled infection requiring IV antibiotics will not be eligible
to participate in the study

- Patients on strong CYP3A4 inhibitors must discontinue them at least 1 week prior to
starting irinotecan therapy

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 9/19/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Thorvardur Halfdanarson, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Jason Starr, D.O.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mohamad Sonbol, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
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