Ticilimumab (CP-675,206) in Treating Patients With Stage IIIC or Stage IV Melanoma

NCT00471887 | Completed Phase 2 Results DMC

• 4 other identifiers: 11-0002360UCLA-0606093-01PFIZER-UCLA-0606093-01CDR0000543416
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Monoclonal antibodies, such as ticilimumab (CP-675,206), 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 ticilimumab (CP-675,206) works in treating patients with stage IIIC or stage IV melanoma.

Conditions

Melanoma (Skin)

Keywords

stage III melanoma; stage IV melanoma; recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• Change in Tumor Infiltration by Cluster of Differentiation 8 (CD8) Positive Cytotoxic T Lymphocytes

  Tumor infiltration of cluster of differentiation 4 and cluster of differentiation 8 (CD4+ and CD8+) cells (intratumoral and peritumoral) was assessed by immunohistochemistry of tumor tissue obtained through biopsy before and after administration of tremelimumab. Up to 10 randomly selected fields per sample were analyzed.

  pre treatment - post treatment at 24 months

Secondary Outcomes (5)

• Change in Intratumoral Expression of the Proteins HLA-DR, CD45RO, Ki67 and FOXP3 and FOXP3"

  pre treatment - post treatment at 24 months

• Differences in Morphological and Gene Expression Profiling Studies in Peripheral Blood Mononuclear Cells

  pre treatment - post treatment at 24 months

• Changes in the Protein Content in Peripheral Blood With an Increase in Proinflammatory Cytokines and Chemokines

  pre treatment - post treatment at 24 months

• Overall Response (Complete or Partial Response) as Measured by RECIST Criteria

  pre treatment - post treatment at 24 months

• Overall Safety Profile as Measured by NCI CTCAE v2.0

  pre treatment - post treatment at 24 months

Study Arms (1)

Treatment-Single Arm

EXPERIMENTAL

See intervention descriptions

Biological: CP-675,206

Interventions

CP-675,206 BIOLOGICAL

Patients will receive intravenous administration of CP-675,206 at a dose of 15mg/kg on Day 1 of an every 90 day cycles. For purposes of treatment visits and scheduling, each cycle is defined as a 90 day period. Patients may receive up to 8 dose (8 cycles) in a 24-month period until progression of disease or intolerable toxicity.

Treatment-Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed melanoma that is surgically incurable and either:
• Stage IIIc melanoma including locally relapsed, satellite, in-transit lesions or bulky draining lymph node metastasis.
• Stage IV melanoma (M1a, M1b, M1c) with accessible lesions for biopsy.
• At least 2 lesions amenable for outpatient biopsies
• No restriction based on prior treatments
• Disease progression after the last dose of prior therapy
• A minimum of one measurable lesion defined as:
• Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors
• Skin lesion(s) selected as non-completely biopsied target lesions that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate bone marrow and hepatic function determined within 30 days prior to enrollment, defined as:
• Absolute neutrophil count \> 1.0 x 10\^9 cells/L
• Platelets \> 90 x 10\^9 /L
• Hemoglobin \> 9 g/L
• Aspartate and alanine aminotransferases \< 2.5 x upper limit of normal (ULN) (\< 5 x ULN, if documented liver metastases are present)

You may not qualify if:

• Received treatment for cancer, including immunotherapy, within one month prior to dosing.
• Previous participation in Pfizer study A3671009: A Phase 3, Open Label, Randomized Comparative Study of CP-675,206 and Either Dacarbazine or Temozolomide in Patients with Advanced Melanoma
• Eligible for enrollment to Pfizer A3671008: A Phase 2, Open Label, Single Arm Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of CP-675,206 in Patients with Advanced Refractory and/or Relapsed Melanoma
• History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis or any origin
• Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
• Clinically active brain metastases. Radiological documentation of absence of brain metastases at screening is required for all patients
• Pregnancy or breast-feeding.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Pfizer: collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Related Publications (3)

• von Euw E, Chodon T, Attar N, Jalil J, Koya RC, Comin-Anduix B, Ribas A. CTLA4 blockade increases Th17 cells in patients with metastatic melanoma. J Transl Med. 2009 May 20;7:35. doi: 10.1186/1479-5876-7-35.

  PMID: 19457253 BACKGROUND

• Huang RR, Jalil J, Economou JS, Chmielowski B, Koya RC, Mok S, Sazegar H, Seja E, Villanueva A, Gomez-Navarro J, Glaspy JA, Cochran AJ, Ribas A. CTLA4 blockade induces frequent tumor infiltration by activated lymphocytes regardless of clinical responses in humans. Clin Cancer Res. 2011 Jun 15;17(12):4101-9. doi: 10.1158/1078-0432.CCR-11-0407. Epub 2011 May 10.

  PMID: 21558401 DERIVED

• Comin-Anduix B, Sazegar H, Chodon T, Matsunaga D, Jalil J, von Euw E, Escuin-Ordinas H, Balderas R, Chmielowski B, Gomez-Navarro J, Koya RC, Ribas A. Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. PLoS One. 2010 Sep 15;5(9):e12711. doi: 10.1371/journal.pone.0012711.

  PMID: 20856802 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

tremelimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Antoni Ribas, MD
• Organization: UCLA

aribas@mednet.ucla.edu

310-206-3928

Study Officials

• Antoni Ribas, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• John A. Glaspy, MD, MPH

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• James S. Economou, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2007
• First Posted: May 10, 2007
• Study Start: January 1, 2007
• Primary Completion: July 1, 2011
• Study Completion: March 1, 2015
• Last Updated: October 26, 2020
• Results First Posted: October 26, 2020

Record last verified: 2016-01

Locations

US (1)