Trial Title:
Study of Senaparib in Combination With Temozolomide
NCT ID:
NCT06617923
Condition:
Ovary Cancer
Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Conditions: Official terms:
Fallopian Tube Neoplasms
Ovarian Neoplasms
Temozolomide
Conditions: Keywords:
ovarian
endometrioid
clear cell
ARID1A mutation
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
two-stage, non-randomized
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Senaparib
Description:
Participants will receive orally 80mg daily Days 1-28 of a 28 day cycle.
Arm group label:
Treatment
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Participants will receive orally 20mg daily Days 1-21 of a 28 day cycle.
Arm group label:
Treatment
Other name:
TMZ
Summary:
This is a study to test the effectiveness (anti-tumor activity) of the combination of the
study drugs, Senaparib and Temozolomide.
Detailed description:
This is a single-arm phase 2, two-stage, non-randomized multicenter Phase 2 study
designed to evaluate the clinical activity (response frequency) of senaparib and
temozolomide (TMZ) in patients with recurrent or persistent clear cell or endometrioid
ovarian cancer.
Up to 18 adult female subjects will be enrolled and receive senaparib 80mg orally daily
Days 1-28 and TMZ 20mg daily Days 1-21 of a 28 day cycle. Tumor assessments will be
performed every 8 weeks for first 3 cycles then every 12 weeks thereafter until
progressive disease is confirmed. Treatment will continue until either unacceptable
toxicity, progression of disease, or withdrawal of consent.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent
document. Legally authorized representatives may sign and give informed consent on
behalf of study participants.
- Pathologically (histologically or cytologically) confirmed diagnosis of recurrent or
persistent clear cell or endometrioid ovarian, fallopian tube, or primary peritoneal
carcinoma. Histologic documentation (via the pathology report) indicating at least
50% endometrioid or clear cell morphology is required.
- Presence of an ARID1A pathologic variant or likely pathogenic variant identified by
next generation sequencing (NGS) tests (per criteria below)
- Pathogenic or likely pathogenic ARID1A variant identified NGS tests performed
by the labs listed on https://ecog-acrin.org/nci-match-eay131-designated-labs
will be considered confirmed for the purposes of this study.
- Pathogenic ARID1A mutation identified by other NGS tests will need to be
confirmed by the study PI prior to enrollment.
- All patients must have measurable disease, according to RECIST v1.1. Measurable
disease is defined as at least one lesion that can be accurately measured in at
least one dimension (longest diameter to be recorded for non-nodal lesions) as ≥20
mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers
by clinical exam. To be considered pathologically enlarged and measurable, a lymph
node must be ≥15 mm in short axis when assessed by CT scan or MRI (CT scan slice
thickness recommended to be no greater than 5 mm). See Section 12 for the evaluation
of measurable disease.
- Patients who have received radiation must have evidence of measurable disease
outside of the radiation field or have documented progression after radiation
at the time of enrollment.
- Patients must have received at least two prior cytotoxic regimens or have
platinum-resistant (defined as having progressed within 6 months of last platinum
therapy) or platinum-refractory (having progressed during primary platinum therapy)
disease.
- Participants can have received no more than 3 prior lines of cytotoxic therapy
(any agent that targets the genetic and/or mitotic apparatus of dividing cells,
resulting in dose-limiting toxicity to the bone marrow).
- Unlimited prior hormonal therapy, targeted therapy (including immunotherapy) or
antiangiogenic therapy will be permitted.
- Patients must have completed prior therapy as detailed below:
- Prior Therapy Time from last prior therapy to study treatment start date
Chemotherapy (except nitrosoureas or mitomycin C) ≥ 28 days; Nitrosoureas or
mitomycin C ≥ 42 days; Small molecule inhibitors ≥ 28 days; Monoclonal
antibodies ≥ 28 days; Immunotherapy ≥ 28 days; Radiotherapy (RT) ≥ 28 days from
last local site RT ≥ 28 days from stereotactic radiosurgery; ≥ 12 weeks from
craniospinal ≥50% radiation of pelvis or total body irradiation Radiation
related side effects must have resolved prior to study enrollment Endocrine
therapy ≥ 7 days
- Ability to take oral medications and not have gastrointestinal illnesses that would
preclude absorption of senaparib or TMZ as judged by the treating physician.
- Patients assigned female at birth, age ≥18 years. Because no dosing or adverse event
data are currently available on the use of senaparib and TMZ in patients <18 years
of age, children are excluded from this study, but will be eligible for future
pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%, see
Appendix A).
- Patients must have adequate organ and marrow function as defined below:
- Absolute Neutrophil Count ≥1,000/microliter (mcL);
- Differential Differential with no clinically significant morphologic
abnormalities on complete blood count (CBC) testing.
- Manual differential is encouraged, if clinically indicated, and in cases where
an automated differential is abnormal.
- Hemoglobin ≥9 g/dL;
- Platelets ≥100,000/mcL;
- aspartate transferase (AST) (SGOT) or Alanine Transaminase (ALT) (SGPT) ≤3 ×
institutional ULN;
- Total Bilirubin ≤1.5 × institutional ULN; Direct bilirubin ≤ ULN for subjects
with total bilirubin > 1.5 x ULN (patients with isolated indirect bilirubin
elevations and a history of Gilbert's Syndrome are eligible)
- Creatinine -OR- Glomerular Filtration Rate ≤ institutional upper limit normal
(ULN) -OR- ≥50 mL/min/1.73 m2 for patients with creatinine levels above
institutional ULN
- Because of the potential DNA damaging effects in a developing human fetus with the
study treatment, participants of childbearing potential 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 including for one month
after last dose of senaparib or temozolomide. Should a woman become pregnant or
suspect she is pregnant while she is participating in this study, she should inform
her treating physician immediately. Theoretically, CYP3A induction with senaparib
use may result in the loss of efficacy in hormonal contraceptives, thus a barrier
method of contraception must be used in addition to hormonal contraceptives due to
the potential drug-drug interaction with senaparib. Note: All females will be
considered to be of childbearing potential unless postmenopausal (amenorrheic for at
least 12 consecutive months, in the appropriate age group, and without other known
or suspected cause) or have been sterilized surgically (ie, bilateral tubal
ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1
month before dosing).
- For patients with known history of chronic hepatitis B virus (HBV) infection, the
HBV viral load must be undetectable on suppressive therapy, if indicated and the
suppressive therapy must not be an excluded concurrent medication.
- Patients with a known history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
the patients are eligible if the patient has an undetectable HCV viral load and the
HCV therapy is not an excluded concurrent medication.
- Patients with treated brain metastases are eligible if follow-up brain imaging ≥ 12
weeks after central nervous system (CNS)-directed therapy shows no evidence of
progression.
- 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, with permission of the
protocol chair.
- 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.
Exclusion Criteria:
- Prior treatment with a poly ADP ribose polymerase (PARP) inhibitor or temozolomide.
- Patients who are currently receiving or have previously received any other
investigational agents within 3 weeks prior to entering the study.
- Patients who have not recovered (CTCAE v5 grade ≤1) from adverse events due to
agents administered more than 4 weeks earlier, unless those events are deemed to
have returned to baseline, are irreversible, or are unlikely to develop into a
life-threatening condition at the permission of the Protocol Chair (e.g., alopecia).
- Patients who have any of the following:
- A prior history of myeloid malignancies, including myelodysplastic syndrome
(MDS).
- Abnormalities known to be associated with MDS (e.g. del 5q, chr 7 abn) and
myeloproliferative neoplasms (MPN) (e.g. JAK2 V617F) observed in cytogenetic
testing and DNA sequencing.
- A prior history of T-cell lymphoblastic lymphoma/lymphoblastic leukemia
(T-ALL).
- Patients with clinical or radiographic evidence of bowel obstruction.
- Severe, active comorbidity per the treating investigator's clinical discretion.
- Pregnant or lactating patients.
- Patients with known human immunodeficiency virus (HIV) infection are ineligible
because the treatments involved in this protocol may be immunosuppressive,
increasing the risk of lethal infections in this patient population.
- Patients with known, untreated brain metastases, as progressive neurologic
dysfunction may develop that would confound the evaluation of neurologic and other
adverse events.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to senaparib or temozolomide.
- Strong CYP3A4 inhibitors or inducers should not be used within 3 days of Day 1
dosing until the end of study. Moderate CYP3A4 inhibitors or inducers should be used
with caution.
Because the lists of these agents are constantly changing, it is important to regularly
consult a frequently updated list such as http://medicine.iupui.edu/
clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference
may also provide this information. 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.
- Uncontrolled intercurrent illness including, but not limited to, the following:
- ongoing or active infection, including latent tuberculosis infection,
- clinically significant GI disease (such as active Crohn's disease or ulcerative
colitis),
- recent or significant cardiovascular disease (defined as any major CV event
within the previous 6 months including myocardial infarction, unstable angina,
cardiac arrhythmia, stroke, Pulmonary Embolism (PE), or New York Heart
Association Class III or IV heart failure),
- history of liver function abnormality requiring investigation, drug induced
liver injury, chronic liver disease, excessive alcohol consumption or chronic
alcohol-induced disease,
- psychiatric illness/social situations that would limit compliance with study
requirements, or
- any other severe acute or chronic medical condition or laboratory abnormality
that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation
of study results and, in the judgment of the investigator, would make the
patient inappropriate for entry into this study
- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects of senaparib and temozolomide. Because there is an unknown
but potential risk for adverse events in nursing infants secondary to treatment of
the mother with these agents, breastfeeding should be discontinued if the mother is
treated on study. These potential risks may also apply to other agents used in this
study.
Gender:
Female
Gender based:
Yes
Gender description:
Women with clear cell or endometrioid ovarian, fallopian tube, or primary peritoneal
cancer.
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
December 2024
Completion date:
December 2029
Lead sponsor:
Agency:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
Impact Therapeutics
Agency class:
Other
Source:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06617923
