Clinical trial NCT05838521: A Study of Sacituzumab Govitecan (IMMU-132) in Patients With Recurrent or Persistent Cervical Cancer
Official title: A Phase II Evaluation of Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2-SN-38 Antibody-drug Conjugate in Patients With Recurrent or Persistent Cervical Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cervical Cancer
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2023-05-01
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132) in subjects with recurrent or persistent cervical cancer.

Detailed description: This is an open-label, Phase 2 study designed to assess the clinical activity of sacituzumab govitecan in subjects with recurrent or persistent cervical cancer.

Eligibility criteria: Inclusion Criteria:

* Patients must have radiologically confirmed (i.e., CAT scan and/or MRI) persistent or recurrent histologically confirmed cervical cancer of epithelial origin who have progressed following at least one prior chemotherapy treatment regimen.

  * Must have availability of archival tumor tissue FFPE block for TROP-2 testing
  * Chemotherapy administered concurrent with primary radiation (i.e., weekly cisplatin) is not counted as a systemic chemotherapeutic regimen for management of persistent or recurrent carcinoma of the cervix.
* All patients must have measurable disease.
* Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST v1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence following completion of radiation therapy.
* After undergoing surgery, patients may be optimally or sub optimally debulked.
* Patients with measurable recurrent disease of any previous substage (I-IV) are eligible to enrollment.
* Patients must have adequate bone marrow function: WBC greater than or equal to 3,000/ul, Platelets greater than or equal to 75,000/ul, Granulocytes greater than or equal to 1500/ul.
* Patients must have adequate renal function: creatinine less than or equal to 2.0 mg/dL.
* Patients must have adequate hepatic function: bilirubin ≤ 1.5 institutional upper limit of normal, aspartate aminotransferase \[AST\], and alanine aminotransferase \[ALT\] ≤ 2.5 × IULN or ≤ 5 × IULN if known liver metastases
* Patients must have an ECOG performance status of 0 or 1.
* Patients must have signed an approved informed consent.
* Patients must be at least 2 weeks beyond prior treatment (chemotherapy, investigational drugs including small molecular inhibitors, endocrine therapy, immunotherapy and/or radiation therapy) or major surgery.
* Patients must be at least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids \< or equal to 20 mg prednisone or equivalent daily are permitted)
* Patients must have recovered from all acute toxicities to Grade 1 or less from adverse events due to a previously administered agent Note: Patients with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may 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
* Patients with recurrent disease may have received no more than 2 prior chemotherapies for treatment of their cervical cancer.
* Patients may have received prior immunotherapy therapy alone or in combination with chemotherapy. A 4-week washout period is required between prior immunotherapy treatment and first dose of sacituzumab govitecan.
* Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the study entry and be practicing an effective form of contraception during the study and until conclusion of 12-week post-treatment evaluation period.
* Patients must be at least 18 years of age.

Exclusion Criteria:

* Patients with a positive serum pregnancy test or women who are breastfeeding.
* Patients with known hypersensitivity to the study drug, its metabolites, or formulation excipient.
* Patients who require ongoing therapy with or prior use of any prohibited medication(s) such as UGT1A1 inhibitors.
* 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.
* Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers or carcinoma in situ of the cervix, are excluded if there is any evidence of other malignancy being present within the last 5 years.
* Patients with a significant history of cardiac disease within 6 months, i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure (NYHA classification III-IV) or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring antiarrhythmia therapy.
* Patients with known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months
* Patients with any unstable medical issue (including cardiac issues as above, active treatment for symptomatic pulmonary embolism, CVA, renal or hepatic insufficiency, and active infection/sepsis requiring IV antibiotics).
* Have known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking ≤20 mg/day of prednisone or its equivalent. All patients with carcinomatous meningitis are excluded regardless of clinical stability
* Patients who have an uncontrolled seizure disorder, or active neurological disease.
* Have known history of HIV-1 or 2 (or positive HIV-1/2 antibody) with detectable viral load OR taking medications that may interfere with SN-38 metabolism
* Have active HBV or HCV. In subjects with a history of HBV or HCV, subjects with a detectable viral load will be excluded.
* Known hemorrhagic diathesis or active bleeding disorder.
* Patients with Gilbert's disease
* Presence of bulky disease (defined as any single mass \>7 cm in its greatest dimension). Patients with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the study PI.
* Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
* Prior history of intestinal obstruction within 6 months of initiation of study treatment.
* Patients with a history of an anaphylactic reaction to irinotecan or ≥ Grade 3 toxicity to prior irinotecan.
* Have previously received topoisomerase I inhibitors

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 4 Years
Secondary outcomes:
measure: Duration of overall survival (OS)
timeFrame: 6 Years
measure: Duration of progression free survival (PFS)
timeFrame: 6 Years
measure: Durable disease control rate (DDCR)
timeFrame: 6 Years
measure: Assess the safety profile of sacituzumab govitecan in cervical cancer patients (adverse events as assessed by CTCAE v5.0)
timeFrame: 6 Years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
Study officials:
affiliation: Yale University
name: Alessandro D. Santin, MD
role: PRINCIPAL_INVESTIGATOR
References: