Trial Title:
Sacituzumab Govitecan in Combination With Capecitabine for Advanced Gastrointestinal Cancers After Progression on Standard Therapy
NCT ID:
NCT06065371
Condition:
Gastrointestinal Cancer
Conditions: Official terms:
Gastrointestinal Neoplasms
Capecitabine
Conditions: Keywords:
pancreatic cancer
biliary tract cancers
colorectal cancer
esophageal cancer
gastroesophageal cancer
gastric cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
3+3
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Capecitabine
Description:
Capecitabine is a fluoropyrimidine that is metabolized to 5-fluorouracil, which inhibits
thymidylate synthase. Capecitabine is available in white or off-white tablets with doses
of 500mg and 150mg doses. 500mg dose tablets will be used on this trial. Capecitabine
will be ordered as a standard of care and provided commercially.
Arm group label:
Sacituzumab govitecan and capecitabine
Other name:
Xeloda
Intervention type:
Drug
Intervention name:
Sacituzumab govetican
Description:
Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2-expressing cells
and is covalently attached to the topoisomerase I inhibitor SN-38. Sacituzumab govitecan
will be provided by Gilead Sciences.
Sacituzumab govitecan for injection, 180 mg and 200 mg, is available as a powder that is
to be reconstituted with 20 mL of 0.9% Sodium Chloride Injection prior to intravenous
infusion.
Following reconstitution, each single-dose vial of Sacituzumab govitecan results in a
concentration of 10mg/mL with pH of 6.5.
Arm group label:
Sacituzumab govitecan and capecitabine
Other name:
Trodelvy
Summary:
This is a Phase I study to evaluate the safety and tolerability of sacituzumab govitecan
in combination with capecitabine for advanced gastrointestinal cancers after progression
on standard therapy, and to assess correlation of outcomes with the biomarker Trop-2.
Detailed description:
This is a single institution, open-label phase I trial that aims to assess the safety of
combination sacituzumab govitecan plus capecitabine in the treatment of patients with
gastrointestinal cancers after progression on standard therapy. Gastrointestinal cancers
eligible include pancreaticobiliary cancers, colorectal cancers, and upper
gastrointestinal cancers such as esophageal, gastroesophageal junction, and gastric
cancers. The trial follows a 3 + 3 design and has three planned dose levels. The starting
dose of sacituzumab govitecan is 7.5mg/kg intravenously on Days 1 and 8. The starting
dose of capecitabine is 500mg/m2 orally twice daily for two weeks on and one week off.
Plan is accrue a total of 20 patients.
The primary endpoint is the recommended phase 2 dose (RP2D) Secondary Endpoints include
adverse events, objective response rate (ORR), duration of response (DoR),
progression-free survival (PFS), and overall survival (OS), There is an exploratory
endpoint of the correlation between Trop-2 expression and clinical outcomes.
Patients will be recruited from the Gastrointestinal (GI) Medical Oncology clinics within
the Henry Ford Cancer Institute (HFCI) campuses. The study is divided into a Screening
period, Treatment period, End of Treatment (EOT) period, and Follow-up period.
During Screening period patients will provide written informed consent (ICF) to
participate in the study before completing any protocol-specified procedures or
evaluations not considered to be part of the patient's standard care. Procedures that
were performed for standard of care prior to signing informed consent may be used for
screening purposes (e.g., full physical exam) as long as the procedures were completed
within the 28-day screening period. After signing the ICF, patients will be evaluated for
entry criteria during the screening period within 28 days before administration of study
drugs. Rescreening after screen failure will be allowed.
Treatment will continue until unacceptable toxicity, death, progression of disease (PD)
per RECIST 1.1, Investigator's decision to discontinue treatment, the patient withdraws
consent, is lost to follow-up, or Institution decides to terminate the trial. Patients
with PD per RECIST 1.1 but with otherwise stable or improved performance and clinical
status may continue to be treated in the event of a perceived benefit per Investigator;
see Section "Treatment beyond progression". Patients with a partial response (PR) or
stable disease (SD) will continue to receive treatment until achievement of a confirmed
complete response (CR), disease progression, or intolerance to therapy. It is at the
discretion of the Investigator to continue treating patients with a confirmed CR.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Female or male patients, 18 years of age or older, able to understand and give
written informed consent
- Patients with the histologically or cytologically documented metastatic
adenocarcinoma of gastrointestinal origin, including gastroesophageal, colorectal,
and pancreaticobiliary that have failed standard therapy
- Adequate hematologic counts without transfusional or growth factor support within 2
weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC)
≥ 1500/mm3, and platelets ≥ 100,000/μL).
- Adequate hepatic function (bilirubin ≤ 1.5x upper limit normal (ULN), aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN or ≤ 5xULN if
known liver metastases, and serum albumin > 3 g/dL).
- Adequate renal function (Creatinine clearance ≥ 30 mL/min as assessed by the
Cockcroft-Gault equation.
- Male and female patients of childbearing potential who engage in heterosexual
intercourse must agree to use protocol-specified method(s) of contraception. Females
of childbearing potential must not have had unprotected sexual intercourse within 30
days before study entry and must agree to use a highly effective method of
contraception (total abstinence [if it is her preferred and usual lifestyle], a
contraceptive implant, an oral contraceptive, or have a vasectomized partner with
confirmed azoospermia) throughout the entire study period and for 6 months after
study drug discontinuation. For sites outside of the European Union (EU), it is
permissible that if a highly effective method of contraception is not appropriate or
acceptable to the subject, then the subject must agree to use a medically acceptable
method of contraception, ie, double barrier methods of contraception such as condom
plus diaphragm or cervical/vault cap with spermicide. If currently abstinent, the
subject must agree to use a highly effective method as described above if she
becomes sexually active during the study period or for 6 months after study drug
discontinuation. Females who are using hormonal contraceptives must have been on a
stable dose of the same hormonal contraceptive product for at least 28 days before
dosing and must continue to use the same contraceptive during the study and for 6
months after study drug discontinuation.
- Male subjects who are partners of women of childbearing potential must use a condom
and spermicide and their female partners, if of childbearing potential, must use a
highly effective method of contraception (see methods described above in Inclusion
Criterion 15) beginning at least 1 menstrual cycle prior to starting study drug,
throughout the entire study period, and for 3 months after the last dose of study
drug, unless the male subjects are totally sexually abstinent or have undergone a
successful vasectomy with confirmed azoospermia or unless the female partners have
been sterilized surgically or are otherwise proven sterile.
- Willing and able to comply with the requirements and restrictions in this protocol
Exclusion Criteria:
- Positive serum pregnancy test or women who are breastfeeding.
- Known hypersensitivity to the study drug(s), its metabolites, or formulation
excipient.
- Requirement for ongoing therapy with or prior use of any prohibited medications
listed in protocol.
- Have had a prior anticancer biologic agent within 4 weeks prior to enrolment or have
had prior chemotherapy, targeted small molecule therapy, or radiation therapy within
2 weeks prior to enrollment and have not recovered (i.e., ≥ Grade 2 is considered
not recovered) from adverse events (AEs) at the time of study entry. Note: patients
with any grade neuropathy or alopecia are an exception to this criterion and will
qualify for the study. Note: if patients received major surgery, they must have
recovered adequately from the toxicity and/or complications from the intervention
prior to starting therapy.
- Have previously received topoisomerase 1 inhibitors.
- Have an active second malignancy. Note: patients with a history of malignancy that
have been completely treated, with no evidence of active cancer for 3 years prior to
enrolment, or patients with surgically cured tumors with low risk of recurrence
(e.g., nonmelanoma skin cancer, histologically confirmed complete excision of
carcinoma in situ, or similar) are allowed to enroll.
- Have unstable brain metastases. Note: Patients with stable brain metastasis can be
included. "Stable" brain metastases may be defined as: Prior local treatment by
radiation, surgery, or stereotactic surgery, imaging - stable or decreasing size
after such local treatment, clinically stable signs and symptoms for at least 4
weeks, ≥2 weeks from discontinuation of anti-seizure medication. Patient may receive
low and stable doses of corticosteroids ≤ 20 mg prednisone or equivalent daily. It
should be confirmed by MRI/CT scan that patient has had stable brain metastasis for
4 weeks prior to treatment.
- Met any of the following criteria for cardiac disease:
- Myocardial infarction or unstable angina pectoris within 6 months of enrolment.
- History of serious ventricular arrhythmia (ie, ventricular tachycardia or
ventricular fibrillation), high-grade atrioventricular block, or other cardiac
arrhythmias requiring antiarrhythmic medications (except for atrial
fibrillation that is well controlled with antiarrhythmic medication); history
of QT interval prolongation.
- New York Heart Association (NYHA) class III or greater congestive heart failure
or left ventricular ejection fraction of < 40%.
- Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease)
or GI perforation within 6 months of enrolment.
- Have active serious infection requiring antibiotics.
- Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody, if done at
screening) with detectable viral load OR taking medications that may interfere with
SN-38 metabolism.
- Have active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a
history of HBV or HCV, patients with detectable viral loads will be excluded.
- Patients who test positive for hepatitis B surface antigen (HBsAg). Patients
who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA
by quantitative polymerase chain reaction (PCR) for confirmation of active
disease.
- Patients who test positive for HCV antibody. Patients who test positive for HCV
antibody will require HCV RNA by quantitative PCR for confirmation of active
disease. Patients with a known history of HCV or a positive HCV antibody test
will not require a HCV antibody at screening and will only require HCV RNA by
quantitative PCR for confirmation of active disease.
- Patients who test positive for HIV antibody.
- Have other concurrent medical or psychiatric conditions that, in the investigator's
opinion, may be likely to confound study interpretation or prevent completion of
study procedures and follow- up examinations.
- Any medical condition that, in the investigator's or sponsor's opinion, poses an
undue risk to the patient's participation in the study [list examples as necessary].
- Use of other investigational drugs (drugs not marketed for any indication) within 28
days or 5 half-lives (whichever is longer) of first dose of study drug.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
November 2024
Completion date:
May 2026
Lead sponsor:
Agency:
Henry Ford Health System
Agency class:
Other
Collaborator:
Agency:
Gilead Sciences
Agency class:
Industry
Source:
Henry Ford Health System
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06065371
