Clinical Trials /

A Study of Sacituzumab Govitecan (IMMU-132) in Endometrial Carcinoma

NCT04251416

Description:

This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132) in subjects with persistent or recurrent endometrial carcinoma.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Sacituzumab Govitecan (IMMU-132) in Endometrial Carcinoma
  • Official Title: A Phase II Evaluation of Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2-SN-38 Antibody-drug Conjugate, in Patients With Persistent or Recurrent Endometrial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2000026850
  • NCT ID: NCT04251416

Conditions

  • Endometrial Carcinoma

Interventions

DrugSynonymsArms
Sacituzumab GovitecanIMMU-132Sacituzumab Govitecan

Purpose

This is a non-randomized Phase 2 study of sacituzumab govitecan (IMMU-132) in subjects with persistent or recurrent endometrial carcinoma.

Detailed Description

      This is an open-label, Phase 2 study designed to assess the clinical activity of sacituzumab
      govitecan in subjects with persistent or recurrent endometrial carcinoma with elevated Trop-2
      expression.
    

Trial Arms

NameTypeDescriptionInterventions
Sacituzumab GovitecanExperimentalSacituzumab govitecan will be administered at 10 mg/kg weekly as an infusion for 2 consecutive weeks (2 weekly doses plus 1 week without treatment represents a single 3 week cycle). Treatment can be continued without a rest period in the absence of progression of disease or unacceptable toxicity.
  • Sacituzumab Govitecan

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have radiologically confirmed (ie, CAT scan and/or MRI) persistent or
             recurrent EC of epithelial origin that has progressed after prior platinum based
             chemotherapy or is refractory to platinum-based chemotherapy and has at least 2+
             staining for Trop-2.

               -  Must have availability of archival tumor tissue FFPE block for TROP-2 testing or
                  newly acquired biopsy (FFPE block) from a metastatic site. Bone biopsies are not
                  allowed.

          -  The diagnosis must be histologically confirmed by a gynecologic pathologist.

          -  All patients must have measurable disease. Measurable disease is defined as lesions
             which can be measured by physical examination or by means of medical imaging
             techniques. Measurable disease is defined as at least one lesion that can be
             accurately measured in at least one dimension (longest dimension to be recorded). Each
             lesion must be ≥ 20 mm when measured by conventional techniques, including palpation
             or plain x-ray, or ≥ 10 mm when measured by spiral CT and/or MRI. Ascites and pleural
             effusions are not to be considered 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 X laboratory normal.
             SGOT/SGPT ≤ 3 X laboratory normal or ≤ 5 X laboratory normal 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 ≤ 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 multiple prior chemotherapies for
             treatment of their endometrial 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:

          -  Have an active second malignancy. Note: Patients with a history of malignancy that has
             been completely treated, with no evidence of active cancer for 3 years prior to
             enrollment, or subjects with surgically-cured tumors with low risk of recurrence are
             allowed to enroll.

          -  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 a known history of HIV-1/2 with uncontrolled viral load and on 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.

          -  Patients with active ≥ grade 2 anorexia, nausea or vomiting, diarrhea, and/or signs of
             intestinal obstruction.

          -  Prior history of clinically significant bleeding, intestinal obstruction, or GI
             perforation within 6 months of initiation of study treatment.

          -  Patients with a history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI
             toxicity to prior irinotecan.

          -  Patients who have previously received topoisomerase I inhibitors.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:4 Years
Safety Issue:
Description:Objective response rate (complete response and partial response rates) by RECIST1.1 criteria in patients with persistent or recurrent endometrial carcinoma (EC)

Secondary Outcome Measures

Measure:Duration of overall survival (OS)
Time Frame:6 Years
Safety Issue:
Description:Overall survival is defined as the duration of time from study entry to death or the date of last contact.
Measure:Duration of progression free survival (PFS)
Time Frame:6 Years
Safety Issue:
Description:Progression free survival is defined as the duration of time from study entry to time of progression, death, or is censored at date of last disease assessment
Measure:Durable disease control rate (DDCR)
Time Frame:6 Years
Safety Issue:
Description:The percentage of patients who have achieved complete response, partial response, and stable disease
Measure:Assess the safety profile of sacituzumab govitecan in endometrial cancer patients (adverse events as assessed by CTCAE v5.0)
Time Frame:6 Years
Safety Issue:
Description:Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Alessandro Santin

Last Updated

January 30, 2020