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

Overview

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.

Interventions

• Drug Sacituzumab govitecan
  This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132).

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: 4 Years]

Secondary outcome measures (4)

• Duration of overall survival (OS) [Time frame: 6 Years]
• Duration of progression free survival (PFS) [Time frame: 6 Years]
• Durable disease control rate (DDCR) [Time frame: 6 Years]
• Assess the safety profile of sacituzumab govitecan in cervical cancer patients (adverse events as assessed by CTCAE v5.0) [Time frame: 6 Years]

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.
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• Smilow Cancer Hospital at Yale New Haven — New Haven
• Cleveland Clinic — Cleveland

Identifiers

NCT: NCT05838521 · 2000023639

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗