Trial Title:
ZN-c3 + Gemcitabine in Pancreatic Cancer
NCT ID:
NCT06015659
Condition:
Advanced Pancreatic Adenocarcinoma
Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Gemcitabine
Conditions: Keywords:
Advanced Pancreatic Adenocarcinoma
Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zentalis
Description:
Small molecule inhibitor of the WEE1 tyrosine kinase, tablet taken orally per protocol.
Arm group label:
ZN-c3 + Gemcitabine
Other name:
Zn-c3, KP-2638, azenosertib, C29H34N8O2.
Intervention type:
Drug
Intervention name:
Gemzar
Description:
Nucleoside metabolic inhibitor, per standard care via intravenous infusion.
Arm group label:
ZN-c3 + Gemcitabine
Other name:
Gemcitabine hydrochloride, FF 10832, LY188011, C9H11F2N3O4 - HCl
Summary:
This study is being done to test the safety and effectiveness of combining ZN-c3 and
Gemcitabine in participants with pancreatic cancer.
The names of the study drugs involved in this study are:
- ZN-c3 (a small molecule inhibitor of the WEE1 tyrosine kinase)
- Gemcitabine (a nucleoside metabolic inhibitor)
Detailed description:
This is an open label, single arm phase 2 trial evaluating ZN-c3 combined with
gemcitabine in second-line advanced pancreatic cancer. There are lab experiments that
show that pancreatic cancer cells can respond to a combination of ZN-c3, an experimental
drug, with gemcitabine.
The U.S. Food and Drug Administration (FDA) has not approved ZN-c3 as a treatment for any
disease. The FDA has approved gemcitabine as a treatment option for advanced pancreatic
cancer.
The research study procedures include screening for eligibility, study treatment
including evaluations and follow up visits, radiological scans (Computerized Tomography,
Magnetic Resonance Imaging, or Positron Emission Tomography), blood tests,
electrocardiogram, and tumor biopsy.
It is expected that about 34 people will take part in this research study.
The Lustgarten Foundation for Pancreatic Research and Stand Up to Cancer are supporting
this research study by providing funding to conduct the study. Zentalis is supplying the
study drug, ZN-c3.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participants must have a pathologically confirmed advanced pancreatic adenocarcinoma
that is not curable with standard approaches based on the judgement of the treating
investigator. Patients with metastatic pancreatic cancer and unresectable pancreatic
cancer are eligible.
- Patients must have progressed or not tolerated a platinum-based regimen prior to
enrolling on the trial.
- Patients must have received no more than 1 prior lines of platinum-based
chemotherapy in the metastatic setting. Therapy given in the adjuvant or neoadjuvant
setting is counted as a prior therapy if it occurred less than 6 months before
cancer recurrence or progression.
- Age ≥ 18 years. As no dosing or adverse event data are currently available in
participants < 18 years of age, children and adolescents are excluded from this
study.
- ECOG performance status of 0 or 1 (see Appendix A) with no deterioration over the
previous 2 weeks prior to day of first dosing (Cycle 1, Day 1).
- Participants must have adequate organ and marrow function as defined below:
- Absolute neutrophil count ≥ 1,500/mm3
- Platelets ≥ 100,000/mm3 excluding measurements obtained within 3 days after
transfusion of platelets
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN); or total
bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with documented
Gilbert's Syndrome.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Albumin
≤2.5 x institutional ULN; ≤ 5 × institutional ULN if liver metastases ≥ 2.7
g/dL
- Creatinine clearance (CrCl) ≥ 50 ml/min based on Cockroft-Gault method
- Participants must have measurable disease by RECIST v. 1.1 criteria and be willing
to undergo a pre-treatment and on-treatment tumor biopsy. The biopsy requirement can
be waived only with approval from the sponsor-investigator.
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated, unless there
is a drug-drug interaction with study medication.
- Patient has read and understands the informed consent form (ICF) and has been given
written ICF prior to any study procedures which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
- Female patients who are not of child-bearing potential* and women of childbearing
potential who agree to use adequate contraceptive measures prior to the first dose
and for 90 days after the last dose of ZN-c3, and who have a negative serum or urine
pregnancy test within 14 days prior to the start of study treatment.
--Evidence of non-childbearing status, defined as below:
- Women who are surgically sterile (i.e., have undergone bilateral salpingectomy,
bilateral oophorectomy, or complete hysterectomy).
- Age ≥50 years with any one or more of the conditions below:
- Amenorrheic for 12 months or more following cessation of all hormonal
replacement therapy
- Had radiation-induced menopause with last menses >1 year ago
- Had chemotherapy-induced menopause with last menses >1 year ago
- Age <50 if amenorrhoeic for 12 months or more following cessation of all
hormonal replacement therapy and if luteinizing hormone and follicle-
stimulating hormone levels are in the post-menopausal range per institutional
standards of practice.
- Male patients should be willing to abstain or use barrier contraception (i.e.,
condoms) for the duration of the study drug exposure and for 90 days after the last
dose of ZN- c3 after study treatment discontinuation.
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For participants with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load, unless
there is a drug-drug interaction with study medication.
Exclusion Criteria:
- Patients who have previously received a WEE1 inhibitor are not eligible.
- Patients who received gemcitabine for incurable pancreatic cancer (locally advanced
unresectable or metastatic) or patients progressing within 6 months of receiving
neoadjuvant/adjuvant gemcitabine.
- Use of an anti-cancer treatment drug ≤ 21 days or 5 half-lives (whichever is
shorter) prior to the first dose of ZN-c3.
- Active use of treatment prescription or non-prescription drugs, or food and herbal
supplements, that are strong/moderate CYP3A4 inhibitors, P-gp inhibitors, or strong
CYP3A4 inducers.
- Any prior palliative radiation to ≥5% of the bone marrow, and must have been
completed and recovered from adverse effects of therapy at least 21 days prior to
the first dose of ZN-c3.
- Participants who have undergone major surgical procedures ≤ 28 days, or minor
surgical procedures ≤ 7 days, of the first dose of ZN-c3. No waiting period is
required following port-a-cath or other central venous access placement.
- Presence of CTCAE v5.0 Grade >1 toxicity from prior therapy (except alopecia,
anorexia or CTCAE grade 2 peripheral neuropathy).
- Patient is unable to swallow oral medications. Note: Patient may not have a
percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral
nutrition (TPN).
- Participants with known malignant central nervous system (CNS) disease other than
neurologically stable, treated brain metastases - defined as metastasis having no
evidence of progression or hemorrhage for at least 2 weeks after the completion of
treatment (including brain radiotherapy). Must be off any systemic corticosteroids
for the treatment of brain metastases for at least 14 days prior to enrollment.
- History of hypersensitivity to compounds of similar chemical or biologic composition
to gemcitabine or ZN-c3.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection*, uncontrolled major seizure disorder, unstable spinal cord compression,
superior vena cava syndrome, or psychiatric illness/social situations that would
limit compliance with study requirements.
- Recurrent, active or suspected infection and/or patients who are predisposed to an
increased risk of severe infection. Patients with infections that require
antibiotics or antifungal agents may be eligible, provided that infection is
resolved and treatment is completed at least 7 days prior to study treatment start.
- Participants with a clinically significant gastrointestinal disorder that in the
opinion of the treating investigator could impact the absorption of the study drugs,
including but not limited to refractory nausea and vomiting, chronic
gastrointestinal disease, inability to swallow the formulated product, or previous
significant bowel resection that would preclude adequate absorption, distribution,
metabolism, or excretion of ZN-c3.
- Participants with a history of a clinically relevant second primary malignancy
within the past 2 years. Exceptions include: resected basal and squamous cell
carcinomas of the skin and completely resected carcinoma in situ of any type.
- Administration of strong or moderate CYP3A4 inhibitors or inducers and P-gp
inhibitors. (See Appendix B)
- Pregnant or lactating women are excluded from this study because gemcitabine/ZN- c3
are anti-cancer agents 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 gemcitabine/ZN-c3, breastfeeding should be
discontinued if the mother is treated with gemcitabine/ZN-c3.
- Any of the following cardiac diseases currently or within 6 months of the first dose
of ZN-c3:
- 12-lead ECG demonstrating a corrected QT interval using Fridericia's formula
(QTcF) of >470 ms, except for subjects with atrioventricular pacemakers or
other conditions (e.g., right bundle branch block) that render the QT
measurement invalid.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Brandon Huffman, MD
Email:
Brandon_Huffman@DFCI.HARVARD.EDU
Investigator:
Last name:
Brandon Huffman, MD
Email:
Principal Investigator
Start date:
November 16, 2023
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Brandon Huffman
Agency class:
Other
Collaborator:
Agency:
Lustgarten Foundation
Agency class:
Other
Collaborator:
Agency:
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Agency class:
Industry
Collaborator:
Agency:
Stand Up To Cancer
Agency class:
Other
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06015659
