Hu3S193 in Treating Women With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Recepta Biopharma
ClinicalTrials.gov Identifier:
NCT00617773
First received: February 15, 2008
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as Hu3S193, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase II trial is studying how well Hu3S193 works in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cavity cancer.


Condition Intervention Phase
Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cancer
Biological: hu3S193
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A PHASE II TRIAL OF Hu3S193 THERAPY FOR PATIENTS WITH PLATINUM REFRACTORY OR PLATINUM RESISTANT EPITHELIAL OVARIAN, PRIMARY PERITONEAL AND FALLOPIAN TUBE CANCER

Resource links provided by NLM:


Further study details as provided by Recepta Biopharma:

Primary Outcome Measures:
  • Best Overall Response [ Time Frame: From start of study treatment until the end of Cycle 1 (8 weeks), Cycle 2 (16 weeks) or Cycle 3 (24 weeks). ] [ Designated as safety issue: No ]

    Best response recorded from the start of treatment until disease progression/recurrence. Includes all patients evaluable for efficacy, regardless of used criteria: RECIST or CA-125 (Cancer Antigen 125).

    Evaluation of target lesions: Complete Response (CR), resolution of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD sum) of target lesions, taking as reference the baseline LD sum; Progressive Disease (PD), a 20% increase in LD sum of target lesions or the appearance of new lesion(s); Stable Disease (SD), no sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Evaluation of non-target lesions: CR, resolution of all non-target lesions and normalization of CA-125 level; SD, persistence of one or more non-target lesions and/or maintenance of CA-125 level above the normal limits; PD, appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.



Secondary Outcome Measures:
  • Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: From the first dose of investigational product up to 30 days after the last dose of investigational product ] [ Designated as safety issue: Yes ]
    A listing of all adverse events is located in the Reported Adverse Event module.

  • Number of Participants With Adverse Events Reasonably Related to the Investigational Product (Incidence Greater Than 5%). [ Time Frame: From the first dose of investigational product up to 30 days after the last dose of investigational product ] [ Designated as safety issue: Yes ]
    Adverse events with possible, probable or definite relationship to the investigational product were considered to be reasonably related.

  • Mean Cmax and Cmin of Hu3S193 Relating to the First 4 Doses. [ Time Frame: Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, and 4 of Cycle 1. ] [ Designated as safety issue: No ]
    Cmax = Peak (post-dosing) IP (Investigational Product) plasma concentration. Cmin = Trough (pre-dosing) IP plasma concentration (Cmin). Plasma concentration of Hu3S193 expressed in µg/mL.

  • Mean Cmax and Cmin of Hu3S193 Relating to the First 8 Doses [ Time Frame: Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, 4, 5, 6, 7 and 8 of Cycle 1. ] [ Designated as safety issue: No ]
    Cmax = Peak (post-dosing) IP plasma concentration. Cmin = Trough (pre-dosing) IP plasma concentration (Cmin). Plasma concentration of Hu3S193 expressed in µg/mL.


Other Outcome Measures:
  • Clinical Benefit [ Time Frame: From start of study treatment until the end of Cycle 3 (24 weeks). ] [ Designated as safety issue: No ]

    The clinical benefit was calculated considering all patients with objective response rate (CR + PR) or stable disease (SD) for at least 24 weeks according RECIST or CA-125 if patients were non-assessable or when assessment by RECIST was unknown.

    Clinical benefit = 100% x (Number of patients with objective response + Number of patients with stable disease for at least 24 weeks) / Number of patients included in the efficacy population.

    The evaluation of target and non-target lesions is described at the Outcome Measure titled "Best Overall Response". CR: Complete Response; PR: Partial Response; SD: Stable Disease.


  • Progression Free Survival (PFS) [ Time Frame: From the first day of the investigational product administration until documentation of disease progression or death due to any cause (whichever occurred first). An average of 16.5549 weeks. ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the duration of time from start of treatment to time of disease progression.

  • Overall Survival [ Time Frame: From start of study treatment until death or the date that patients were last known to be alive. An average of 56.126 weeks. ] [ Designated as safety issue: No ]
    Measured from the beginning of therapy until the date of death or for patients without a known date of death, they will be censored at the date they were last known to be alive.

  • 12-Month Survival Rate [ Time Frame: 12 months from the start of study treatment. ] [ Designated as safety issue: No ]
    Rate of patients alive 12 months after starting therapy with the investigational product.


Enrollment: 31
Study Start Date: May 2008
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: hu3S193 Biological: hu3S193
20 mg/m2, intravenous, weekly for a maximum of 3 cycles (of 8 weeks each)

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the efficacy of monoclonal antibody Hu3S193 in women with platinum-resistant/refractory ovarian, fallopian tube, or primary peritoneal cancer, based on RECIST criteria (Response Evaluation Criteria in Solid Tumors).

Secondary

  • To determine the safety of the study drug.
  • To determine the drug pharmacokinetics when administered in multiple weekly injections.

Exploratory analysis

  • Clinical Benefit (objective response rate + tumor stabilization).
  • Progression Free Survival (PFS).
  • Duration of Response.
  • Overall Survival.
  • 12-month survival rate.

OUTLINE: This is a multicenter study.

Patients receive monoclonal antibody Hu3S193 IV over 1 hour once weekly in weeks 1-8. Treatment repeats every 8 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed monthly.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal carcinoma

    • Progressive disease
    • Disease must express Lewis-Y antigen documented by immunohistochemistry in archived or fresh primary or metastatic tumor biopsies
  • Measurable disease, including at least one measurable lesion, according to RECIST criteria or CA-125 (Cancer Antigen-125) > 2 times upper normal limit

    • Pleural effusion, ascites, bone metastases, and lesions located in previously irradiated areas are not considered measurable
  • Disease must be considered platinum-refractory or resistant, meeting any of the following criteria:

    • Platinum-refractory defined as progression during the initial platinum-based chemotherapy regimen or failure to achieve a complete response (e.g., stable disease or partial response) with evidence of progressive disease (by physical examination, radiological exams, or CA-125) during the initial platinum-based chemotherapy
    • Platinum-resistant defined as recurrence within six months of completion of the initial platinum-based regimen (primary platinum-resistance) or recurrence after six months of completion of the initial platinum-based regimen (still considered platinum-sensitive, but incurable by any approach, that will progress to a secondary platinum-resistance scenario) and failure to ≥ 1 re-induction with a platinum-based regimen (secondary platinum-resistance)
  • No high tumor burden, as assessed by the investigator
  • No rapidly progressing disease, as assessed by clinical evaluation
  • No known CNS (Central Nervous System) involvement by tumor

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • Karnofsky performance status > 70%
  • Life expectancy ≥ 12 weeks
  • ANC (absolute neutrophil count) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Serum bilirubin ≤ 2.0 mg/dL
  • AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if with liver metastases)
  • Creatinine ≤ 2.0 mg/dL
  • Prothrombin time < 1.3 times control
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion criteria:

  • NYHA (New York Heart Association) class III or IV heart disease
  • Clinically significant arrhythmias by ECG
  • Myocardial infarction within the past 6 months
  • Any other serious illness, including any of the following:

    • Severe ascites
    • Severe active infections requiring antibiotics
    • Bleeding disorders
    • Chronic inflammatory bowel disease
    • Diseases that might interfere with the collection of accurate results from this study
  • Positive for human anti-human antibodies
  • Prior history of tumor (excluding adequately treated nonmelanoma skin cancer or carcinoma in situ of the uterine cervix)
  • Uncontrolled hypercalcemia (i.e., > 11.5 mg/dL)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from the toxic effects of any prior therapy
  • No concurrent systemic steroids or immunosuppressant agents
  • No more than 1 prior non-platinum-containing regimen for the treatment of platinum-resistant/refractory disease

    • Patients who receive 2 or more different non-platinum-containing chemotherapy regimens for platinum-resistant/refractory disease are not eligible
  • More than 4 weeks since prior and no other concurrent chemotherapy, radiotherapy, radiopharmaceuticals (e.g., ^32P), biological therapy, anti-estrogen therapy (including tamoxifen), immunotherapy, or surgery
  • More than12 weeks since prior investigational agent
  • No prior treatment with a murine or humanized antibody and/or antibody fragment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00617773

Locations
Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
Hospital da Baleia
Minas Gerais, Brazil, 30285-000
Hospital Sao Lucas da PUCRS
Porto Alegre, Brazil, 90610-000
Instituto Nacional de Cancer
Rio de Janeiro, Brazil, 20220-410
Hospital Sirio-Libanes
Sao Paulo, Brazil, 01308-050
Hospital Israelita Albert Einstein
Sao Paulo, Brazil, 05651-901
Hospital das Clinicas FMUSP
Sao Paulo, Brazil, 01246-000
Hospital Alemao Oswaldo Cruz
Sao Paulo, Brazil, 01401-904
Sponsors and Collaborators
Recepta Biopharma
Investigators
Study Chair: Oren Smaletz, MD Recepta Biopharma
  More Information

Additional Information:
No publications provided

Responsible Party: Recepta Biopharma
ClinicalTrials.gov Identifier: NCT00617773     History of Changes
Other Study ID Numbers: RCPOv01-06, RCP-Ov-01.06
Study First Received: February 15, 2008
Results First Received: May 15, 2013
Last Updated: November 1, 2013
Health Authority: United States: Food and Drug Administration
Brazil: National Health Surveillance Agency

Keywords provided by Recepta Biopharma:
recurrent ovarian epithelial cancer
recurrent fallopian tube cancer
recurrent primary peritoneal cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases

ClinicalTrials.gov processed this record on July 22, 2014