Clinical trial NCT00617773: Hu3S193 in Treating Women With Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cancer
Keywords: recurrent ovarian epithelial cancer
recurrent fallopian tube cancer
recurrent primary peritoneal cancer
Lead sponsor: Recepta Biopharma
Sponsor class: INDUSTRY
First posted: 2008-02-18
Enrollment: 31
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: 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.

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 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

Primary outcomes:
measure: Best Overall Response
timeFrame: From start of study treatment until the end of Cycle 1 (8 weeks), Cycle 2 (16 weeks) or Cycle 3 (24 weeks).
Secondary outcomes:
measure: Number of Participants With Adverse Events and Serious Adverse Events
timeFrame: From the first dose of investigational product up to 30 days after the last dose of investigational product
measure: Number of Participants With Adverse Events Reasonably Related to the Investigational Product (Incidence Greater Than 5%).
timeFrame: From the first dose of investigational product up to 30 days after the last dose of investigational product
measure: Mean Cmax and Cmin of Hu3S193 Relating to the First 4 Doses.
timeFrame: Pre-dose (within 10 minutes) and Post-dose (5 minutes after completion of infusion) on weeks 1, 2, 3, and 4 of Cycle 1.
measure: Mean Cmax and Cmin of Hu3S193 Relating to the First 8 Doses
timeFrame: 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.
Other outcomes:
measure: Clinical Benefit
timeFrame: From start of study treatment until the end of Cycle 3 (24 weeks).
measure: Progression Free Survival (PFS)
timeFrame: 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.
measure: Overall Survival
timeFrame: From start of study treatment until death or the date that patients were last known to be alive. An average of 56.126 weeks.
measure: 12-Month Survival Rate
timeFrame: 12 months from the start of study treatment.
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande do Sul
city: Minas Gerais
country: Brazil
facility: Hospital da Baleia
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas FMUSP
city: Sao Paulo
country: Brazil
facility: Hospital Sirio-Libanes
city: Sao Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
Study officials:
affiliation: Recepta Biopharma
name: Oren Smaletz, MD
role: STUDY_CHAIR
References:
citation: Smaletz O, Diz MD, do Carmo CC, Sabbaga J, Cunha-Junior GF, Azevedo SJ, Maluf FC, Barrios CH, Costa RL, Fontana AG, Madrigal V, Wainstein AJ, Yeda FP, Alves VA, Moro AM, Blasbalg R, Scott AM, Hoffman EW. A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Gynecol Oncol. 2015 Aug;138(2):272-7. doi: 10.1016/j.ygyno.2015.05.023. Epub 2015 May 27.