Clinical trial NCT00319748: Study of Immune Response Modifier in the Treatment of Breast, Ovarian, Endometrial and Cervical Cancers
Official title: Phase II Study of 852A Administered Subcutaneously in Patients With Metastatic Refractory Breast, Ovarian, Endometrial and Cervical Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Ovarian Cancer
Endometrial Cancer
Cervical Cancer
Keywords: Breast
Ovarian
Endometrial
Cervical
Metastatic
852A
IRM
Oncology
Metastatic Cervical Cancer
Metastatic Ovarian Cancer
Metastatic Breast Cancer
Metastatic Endometrial Cancer
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2006-04-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the anti-tumor activity of 852A when used to treat metastatic breast, ovarian, endometrial or cervical cancer not responding to standard treatment.

Detailed description: 852A will be administered as a subcutaneous injection (SC) 2 times per week for 12 weeks (24 doses) with provisions for dose escalation or reduction based on tolerability.

Eligibility criteria: Inclusion Criteria:

* Adequate performance status:

  * Breast - Karnofsky score \> 50;
  * Ovarian, endometrial or cervical - Gynecologic Oncology Group (GOG) performance score ≤2
* If female and of childbearing potential, are willing to use adequate contraception (hormonal, barrier method, abstinence) prior to study entry and for the duration of study participation.
* Normal organ function within 14 days of study entry
* Diagnosis of one of the following malignancies:

  * Metastatic breast cancer (BR)
  * Metastatic ovarian cancer (OV)
  * Metastatic endometrial cancer (EM)
  * Metastatic cervical cancer (CX)

Breast Cancer Inclusion Criteria:

* Measurable metastatic disease (\>1cm) in at least one site other than bone-only
* Progression on or failure to respond to at least one previous chemotherapy regimen for metastatic disease
* Progression on prior therapy with a hormonal agent if estrogen receptor or progesterone receptor positive, and/or with trastuzumab if HER2-neu positive. If patient has progressed through hormone or trastuzumab therapy only, must have received one chemotherapy regimen.

Ovarian Cancer Inclusion Criteria:

* Measurable metastatic disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)
* Primary tumor must have been diagnosed histologically as either epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (not borderline or low malignant potential epithelial carcinoma).
* Subjects must have failed at least two previous chemotherapy regimens. Paclitaxel must have been a component of one or both regimens and cisplatin or carboplatin must have been a component of one or both regimens.

Endometrial Cancer Inclusion Criteria:

* Measurable metastatic disease
* Histologically proven recurrent or persistent endometrial cancer that is not amenable to curative treatment with surgery and/or radiation therapy AND has failed 2 previous treatment regimens

Cervical Cancer Inclusion Criteria:

* Measurable metastatic disease
* Histologically proven recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy AND has failed 2 previous treatment regimens.

Exclusion Criteria:

* Had/have the following prior/concurrent therapy:

  * Systemic corticosteroids (oral or injectable) within 7 days of first dose of 852A (topical or inhaled steroids are allowed)
  * Investigational drugs/agents within 14 days of first dose of 852A
  * Immunosuppressive therapy, including cytotoxic agents within 14 days of first dose of 852A (nitrosoureas within 30 days of first dose)
  * Drugs known to induce QT interval prolongation and/or induce Torsades de pointes unless best available drug required to treat life-threatening conditions
  * Radiotherapy within 3 weeks of the first dose of 852A
  * Hematopoietic cell transplantation within 4 weeks of first dose of 852A
  * Evidence of active infection within 3 days of first dose of 852A
  * Active fungal infection or pulmonary infiltrates (prior treated disease stable for 2 weeks is allowable)
  * Cardiac ischemia, cardiac arrhythmias or congestive heart failure uncontrolled by medication
  * History of, or clinical evidence of, a condition which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk
  * Uncontrolled intercurrent or chronic illness
  * Active autoimmune disease requiring immunosuppressive therapy within 30 days
  * Active coagulation disorder not controlled with medication
  * Pregnant or lactating
  * Concurrent malignancy (if in remission, at least 5 years disease free) except for localized (in-situ) disease, basal carcinomas and cutaneous squamous cell carcinomas that have been adequately treated
  * Any history of brain metastases or any other active central nervous system (CNS) disease

Primary outcomes:
measure: Patients With Tumor Response (Response Evaluation Criteria in Solid Tumors) Who Received All 24 Doses of 852A.
timeFrame: after 12 weeks (24 doses of 852A)
Secondary outcomes:
measure: Mean Difference Values for Interleukin 1 Receptor Antagonist (IKL1ra)
timeFrame: Prior to Dose 1 and 6 hours after Dose 1
measure: Mean Difference Values for 10 kDa Interferon-gamma-induced Protein (IP-10)
timeFrame: Prior to Dose 1 and 6 Hours Post-Dose
measure: Mean Difference Values for Macrophage Inflammatory Protein-1 Alpha (MIP-1a)
timeFrame: Prior to Dose 1 and 6 Hours Post-Dose
measure: Mean Difference Values for Macrophage Inflammatory Protein-1 Beta (MIP-1b)
timeFrame: Prior to Dose 1 and 6 Hours Post-Dose
measure: Mean Difference Values for Soluble CD40 Ligand (sCD40L)
timeFrame: Prior to Dose 1 and 6 Hours Post-Dose
measure: Mean Difference Values for Tumor Necrosis Factor-alpha (TNF-a)
timeFrame: Prior to Dose 1 and 6 Hours Post-Dose
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Sarah Cooley, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Masonic Cancer Center, University of Minnesota
name: Melissa A. Geller, MD
role: PRINCIPAL_INVESTIGATOR
References: