Clinical Trials /

Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

NCT01631552

Description:

The primary objective is to evaluate the safety and tolerability of IMMU-132 as a single agent administered in 3-week treatment cycles until unacceptable progression or toxicity, in previously treated patients with advanced epithelial cancer. In Phase II, the primary objective is the evaluation of the safety and efficacy of IMMU-132 administered in 3-week treatment cycles at a dose selected in Phase I, while the secondary objectives include pharmacokinetics and immunogenicity.

Related Conditions:
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Glioblastoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Epithelial Tumor
  • Pancreatic Ductal Adenocarcinoma
  • Prostate Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Thyroid Gland Follicular Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers
  • Official Title: A Phase I/II Study of IMMU-132 (hRS7-SN38 Antibody Drug Conjugate) in Patients With Epithelial Cancers

Clinical Trial IDs

  • ORG STUDY ID: IM-T-IMMU-132-01
  • NCT ID: NCT01631552

Conditions

  • Colorectal Cancer
  • Gastric Adenocarcinoma
  • Esophageal Cancer
  • Hepatocellular Carcinoma
  • Non-small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Ovarian Epithelial Cancer
  • Carcinoma Breast Stage IV
  • Hormone-refractory Prostate Cancer
  • Pancreatic Ductal Adenocarcinoma
  • Head and Neck Cancers- Squamous Cell
  • Renal Cell Cancer
  • Urinary Bladder Neoplasms
  • Cervical Cancer
  • Endometrial Cancer
  • Follicular Thyroid Cancer
  • Glioblastoma Multiforme
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
IMMU-132hRS7-SN38, Sacituzumab GovitecanIMMU-132

Purpose

The primary objective is to evaluate the safety and tolerability of IMMU-132 as a single agent administered in 3-week treatment cycles for up to 8 cycles, in previously treated patients with advanced epithelial cancer.The secondary objectives are to obtain initial data concerning pharmacokinetics, immunogenicity, and efficacy with this dosing regimen. IMMU-132 targets the TROP-2 antigen which is expressed on a variety of cancers. The antibody, RS7, is attached to SN38, which is the active metabolite of irinotecan. This is planned as a multi-center study. In Phase II, up to 130 patients (assessable) in triple-negative breast cancer, up to 100 patients (assessable) in non-small cell and small-cell lung cancer and up to 50 patients (assessable) per other cancer types included in the protocol will be studied at the 10 mg/kg dose.

Detailed Description

      This is a Phase I/II, open-label study of IMMU-132 in previously treated patients with
      advanced epithelial cancers, including ovarian, breast, prostate (hormone refractory), lung
      (non-small cell and small cell), head & neck (squamous cell), esophageal, gastric,
      colorectal, pancreatic, hepatocellular, renal (clear cell), endometrial, cervical,
      urothelial, thyroid cancers and glioblastoma multiforme. Patients receive IMMU-132
      administered once-weekly for the first 2 weeks of 3-week treatment cycles. Patients may
      receive up to a maximum total of 8 cycles (16 doses), but patients with a partial response or
      stable disease at that time, or patients who had achieved an objective response but relapsed
      after discontinuing treatment, may continue to be treated based on physician discretion.
      Treatment will continue until unacceptable toxicity or progression of disease. Both safety
      and efficacy will be assessed.
    

Trial Arms

NameTypeDescriptionInterventions
IMMU-132ExperimentalIMMU-132 (hRS7-SN38) is an Antibody Drug Conjugate where the antibody, hRS7 is attached to SN38. SN38 is the active metabolite of irinotecan (CPT-11).
  • IMMU-132

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female patients, >18 years of age, able to understand and give written
             informed consent.

          -  Histologically or cytologically confirmed epithelial cancer of one of the following
             types:

          -  Colorectal

          -  Gastric adenocarcinoma

          -  Esophageal cancer

          -  Hepatocellular carcinoma

          -  Non-small cell lung cancer

          -  Small cell lung cancer

          -  Ovarian epithelial cancer

          -  Cervical Cancer

          -  Endometrial Cancer

          -  Breast cancer

          -  Hormone-refractory prostate cancer

          -  Pancreatic ductal adenocarcinoma

          -  Head and neck cancers- squamous cell

          -  Renal cell cancer (clear cell)

          -  Urothelial cancers

          -  Glioblastoma multiforme

          -  Follicular thyroid cancer

        (Note: Confirmation of Trop-2 expression by immunohistology or other means is not required,
        but the Sponsor will request tissue specimens from archived materials for determination of
        Trop-2 expression.)

          -  Stage IV (metastatic) disease.

          -  Refractory to or relapsed after at least one prior standard therapeutic regimen
             (Appendix 1 lists approved or standard chemotherapeutic agents for each cancer type.
             Patients who have not received all approved or standard treatments for their cancer
             must be informed that these alternatives to receiving IMMU-132 are available prior to
             consenting to participate in this trial.)

          -  Adequate performance status (ECOG 0 or 1)

          -  Expected survival > 6 months.

          -  Measurable disease by CT or MRI.

          -  At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small
             molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and
             recovered from all acute toxicities to Grade 1 or less (except alopecia).

          -  At least 2 weeks beyond high dose systemic corticosteroids (however, low dose
             corticosteroids < 20 mg prednisone or equivalent daily are permitted).

          -  Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC >
             1,500 per mm3, platelets > 100,000 per mm3).

          -  Adequate renal and hepatic function (creatinine ≤ 2.0 x IULN, bilirubin ≤ 1.5 IULN,
             AST and ALT ≤ 3.0 x IULN or 5 x IULN if know liver metastases).

          -  Otherwise, all toxicity at study entry < Grade 1.

        Exclusion Criteria:

        -•Women who are pregnant or lactating.

          -  Women of childbearing potential and fertile men unwilling to use effective
             contraception during study until conclusion of 12-week post-treatment evaluation
             period.

          -  Patients with Gilbert's disease.

          -  Patients with brain metastases can be enrolled only if treated, non-progressive brain
             metastases and off high-dose steroids (>20 mg prednisone or equivalent) for at least 4
             weeks.

          -  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 medical monitor.

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

          -  Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are
             eligible, while patients with other prior malignancies must have had at least a 3-year
             disease-free interval.

          -  Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.

          -  Known history of unstable angina, MI, or CHF present within 6 months or clinically
             significant cardiac arrhythmia (other than stable atrial fibrillation) requiring
             anti-arrhythmia therapy.

          -  Known history of clinically significant active COPD, or other moderate-to-severe
             chronic respiratory illness present within 6 months.

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

          -  Infection requiring intravenous antibiotic use within 1 week.

          -  history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior
             irinotecan,

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety
Time Frame:During treatment, at the final evaluation and at follow up after treatment
Safety Issue:
Description:Safety will be assessed by monitoring the patient for adverse events, monitoring the change in lab values during and after treatment compared to baseline over an average of 6 months.

Secondary Outcome Measures

Measure:Efficacy
Time Frame:Efficacy will be assessed every 8 weeks during treatment and then every 12 weeks after treatment
Safety Issue:
Description:Efficacy will be evaluated from CT scans (or MRI studies), using RECIST 1.1 to classify tumor response, time to onset of objective response, duration of objective response, and time to progression. Efficacy will be assessed every 8 weeks until the end of treatment or progression of disease and every 12 weeks at the follow up, over an average of 6 months.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Immunomedics, Inc.

Trial Keywords

  • Colorectal (CRC)
  • Gastric adenocarcinoma (GC)
  • Esophageal cancer (EC)
  • Hepatocellular carcinoma (HCC)
  • Non-small cell lung cancer (NSCLC)
  • Small cell lung cancer (SCLC)
  • Ovarian epithelial cancer (OEC)
  • Triple-negative breast cancer (TNBC)
  • Hormone-refractory prostate cancer (HRPC)
  • Pancreatic ductal adenocarcinoma (PDC)
  • Head and neck cancers- squamous cell (SCCHN)
  • Renal cell cancer -clear cell (RCC)
  • Bladder cancer
  • Endometrial Cancer
  • Cervical Cancer
  • Breast cancer
  • Metastatic non-triple negative breast cancer
  • Glioblastoma multiforme
  • Follicular thyroid cancer

Last Updated

June 13, 2017