Phase 1, Open-Label, Dose-Escalation Study of CP-870,893 in Patients With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02225002
Recruitment Status : Completed
First Posted : August 25, 2014
Last Update Posted : August 28, 2018
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania

Brief Summary:
CD40, a member of the Tumor Necrosis Factor receptor superfamily, is expressed on many tumor types, including melanoma, prostate, colon, breast, renal, pancreatic, and nonsmall cell lung cancers. In preclinical models, activation of CD40 results in increased antigen presentation and induction of apoptosis. CD40 is also expressed on antigen presenting cells (APCs) (B cells, dendritic cells, monocytes) and is a key regulator of both cellular and humoral immune responses. Activation of CD40 by CP-870,893, an agonistic anti-CD40 monoclonal antibody, enhances host immune responses and abrogates the growth of tumors independently of the expression of CD40 on tumor cells. Therefore, it is hypothesized that therapeutic intervention with CP-870,893 may be beneficial to a large number of cancer patients either through an immunomodulatory effect or through a direct effect on CD40-positive tumor cells.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: CP-870,893 Phase 1

Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: Phase 1, Open-Label, Dose-Escalation Study of CP-870,893 in Patients With Solid Tumors
Study Start Date : January 2004
Actual Primary Completion Date : February 2006
Actual Study Completion Date : February 2006

Primary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: 2 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Men and women at least 18 years old with advanced solid tumors relapsed or refractory to standard therapy or for whom no effective therapy exists;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1;
  • Adequate bone marrow function documented within 2 weeks prior to treatment, defined as:
  • White blood cell (WBC) count >3000 cells/μL without growth factor support;
  • Absolute neutrophil count (ANC) ≥1500/μL without growth factor support;
  • Platelets >100,000/μL without growth factor support; and
  • Hemoglobin ≥10 g/dL;
  • D-dimer WNL;
  • Adequate renal and hepatic function documented within 2 weeks prior to treatment, defined as:
  • Total bilirubin <1.5 times the upper limit of normal (ULN);
  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <2.5 × ULN;
  • Creatinine clearance (CLcr, measured or calculated) >80 mL/min; and
  • Life expectancy of at least 12 weeks;
  • Fully recovered from the acute effects of prior cancer therapy: 4 weeks for chemotherapy (8 weeks for mitomycin C or nitrosoureas), 10 days for prior palliative radiation therapy or hormonal therapy, and 4 weeks for prior immunotherapy or other biologic therapy; and
  • Signed written informed consent.

Exclusion Criteria:

  • Previously treated with any other agent that targets CD40;
  • Concurrent treatment with any anticancer agent;
  • History of autoimmune disorder, including pemphigus vulgaris, systemic mastocytosis, systemic lupus erythamatosus, dermatomyositis/polymyositis, rheumatoid arthritis, systemic sclerosis, Sjörgen's syndrome, vasculitis/arteritis, Behcet's syndrome, inflammatory boweldisease, autoimmune thyroiditis, multiple sclerosis, or other chronic inflammatory disease;
  • Treatment with any other investigational therapy within 4 weeks prior to baseline;
  • History (within the previous year) of congestive heart failure, stroke, or myocardial infarction;
  • Patients with known hereditary or acquired coagulopathies (eg. hemophilia, von Willebrand's disease, cancer-associated DIC, abnormal D-dimer);
  • Patients with known brain metastases. Patients with clinical evidence suggestive of new brain metastases prior to enrollment are excluded if brain metastases have not been ruled out via CT or MRI. Patients with previously diagnosed brain metastases are eligible if they have completed their CNS treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable;
  • Patients having reproductive potential who are not using an effective method of birth control or who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test during baseline;
  • Known sensitivity to immunomodulating agents or monoclonal antibodies;
  • Alcohol abuse or illicit drug use within 12 months of enrollment;
  • History of serum creatinine ≥2 mg/dL for any duration and for any reason;
  • Patients, other than menstruating females, with urine dipstick 1+ or more positive for blood or 2+ or more positive for protein;
  • Patients with clinically significant presence of granular or cellular casts in centrifuged urine sediment;
  • Patients with renal carcinoma or renal metastases;
  • Patients that have had a partial or complete nephrectomy;
  • Patients requiring dialysis (peritoneal or hemodialysis);
  • Prior treatment with Amphotericin B or cisplatin;
  • Patients with history of insulin-dependent diabetes for greater than 5 years;
  • Concomitant treatment with systemic high dose corticosteroids or treatment with systemic corticosteroids within 4 weeks of baseline;
  • Concomitant treatment with anticoagulants, such as coumadin or heparin, except to maintain patency of in-dwelling catheters;
  • Prior allergic reactions attributed to compounds of similar chemical or biologic composition to study drug (eg, rituximab or immunoglobulin G);
  • Ongoing or active infection;
  • Required the use of systemic antibiotics or antifungals for ongoing or recurrent infections.

Topical use of antibiotics or antifungals is allowed;

  • Other uncontrolled concurrent illness that would preclude study participation; or
  • Psychiatric illness or social situation that would preclude study participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02225002

United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Principal Investigator: Robert Vonderheide, MD Abramson Cancer Center of the University of Pennsylvania

Responsible Party: Abramson Cancer Center of the University of Pennsylvania Identifier: NCT02225002     History of Changes
Other Study ID Numbers: UPCC 10903
First Posted: August 25, 2014    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: August 2018

Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
refractory to standard therapy
no effective therapy exists

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs