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Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma

  1. Jeffrey S. Weber MD, PhD1,†,*,
  2. Hassan Zarour MD2,
  3. Bruce Redman MD3,
  4. Uwe Trefzer MD4,
  5. Steven O'Day MD5,
  6. Alfons J. M. van den Eertwegh MD6,
  7. Ernest Marshall MD7,8,
  8. Stefan Wagner MD9

Article first published online: 17 JUN 2009

DOI: 10.1002/cncr.24473

Issue

Cancer

Cancer

Volume 115, Issue 17, pages 3944–3954, 1 September 2009

Additional Information

How to Cite

Weber, J. S., Zarour, H., Redman, B., Trefzer, U., O'Day, S., van den Eertwegh, A. J. M., Marshall, E. and Wagner, S. (2009), Randomized phase 2/3 trial of CpG oligodeoxynucleotide PF-3512676 alone or with dacarbazine for patients with unresectable stage III and IV melanoma. Cancer, 115: 3944–3954. doi: 10.1002/cncr.24473

Author Information

  1. 1

    Moffitt Cancer Center, Tampa, Florida

  2. 2

    University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

  3. 3

    University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan

  4. 4

    Humboldt University, Berlin, Germany

  5. 5

    The Angeles Clinic Research Institute, Los Angeles, California

  6. 6

    University of Graz, Graz, Austria

  7. 7

    VU Medical Center, Amsterdam, the Netherlands

  8. 8

    University of Kentucky Medical Center, Lexington, Kentucky

  9. 9

    University of Vienna, Vienna, Austria

  1. †

    Fax: (813) 745-4384

*Department of Oncologic Sciences, Moffitt Cancer Center, 12902 Magnolia Drive SRB-2, Tampa, FL 33612

Publication History

  1. Issue published online: 20 AUG 2009
  2. Article first published online: 17 JUN 2009
  3. Manuscript Accepted: 15 DEC 2008
  4. Manuscript Revised: 4 DEC 2008
  5. Manuscript Received: 3 SEP 2008

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Keywords:

  • melanoma;
  • CpG;
  • cytokines;
  • chemotherapy

A phase 2 study was performed with CpG oligodeoxynucleotide PF-3512676 alone, together with dacarbazine (DTIC), and with DTIC alone to assess the objective responses to the regimens in unresectable melanoma. The objective response rates in the 3 PF-3512676 cohorts were not superior to DTIC alone and did not warrant continuation to the phase 3 portion of the study.

Abstract

BACKGROUND:

The primary objective of this phase 2 study was to assess the objective response rate (complete response [CR] + partial responses [PR]), by Response Evaluation Criteria in Solid Tumors, of PF-3512676, a CpG oligodeoxynucleotide, alone in 2 doses or in combination with dacarbazine (DTIC) in patients with unresectable stage IIIB/C or stage IV malignant melanoma, with the aim of selecting an arm to take forward to a phase 3 portion of the study.

METHODS:

A total of 184 patients were randomized to 1 of 4 treatments: PF-3512676 10 mg (low dose), at 40 mg (high dose), 40 mg plus DTIC (850 mg/m2), or DTIC (850 mg/m2) alone. Patients received PF-3512676 subcutaneously weekly in a 3-week cycle and received DTIC intravenously on the first week of the cycle.

RESULTS:

The objective response rate (PR or CR, confirmed or unconfirmed) in the 40 mg + DTIC arm was 16% (7 patients) compared with 8% (3 patients) with DTIC alone. One (2%) patient in the 10-mg and 0 patients in the 40-mg arms achieved an objective response. Best response of CR or PR or stable disease (SD), with no minimum duration defined for SD, was achieved by 15 (33%) patients in the 40 mg + DTIC arm, 15 (38%) patients in the DTIC-only arm, 8 (17%) patients in the 10-mg arm, and 9 (20%) patients in the 40-mg arm. The most frequently reported adverse events were classified as local injection site reactions or systemic flu-like symptoms, specifically fatigue, rigors, and pyrexia.

CONCLUSIONS:

PF-3512676 at the doses used was generally well tolerated. The modest objective response rates observed in all arms did not warrant continuation to the phase 3 portion of the study. Cancer 2009. © 2009 American Cancer Society.

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