A Multicenter, Randomized, Double Blind, Placebo (PB) Controlled Trial of Marimastat (MT) In Patients with Glioblastoma Multiforme (GBM) or Gliosarcoma (GS) Following Completion of Conventional, First-Line Treatment

Heather Jones, MD

University of Pennsylvania Cancer
Last Modified: May 13, 2001

Presenter: S. Phuphanich
Affiliation: The Marimastat Glioblastoma Study Group


    The standard adjuvant therapy for GBM is radiation therapy with or without BCNU. The outcomes of therapy for GBM or GS are poor. There is clearly a need for novel treatment approaches. This study looks a Marimastat administration as an attempt to increase the delivery of cytotoxicity agent to tumor cells without increasing treatment related toxicity. GBM shows prominent endothelial proliferation and Marimastat has been shown to inhibit this process in preclinical studies.

Materials and Methods:

  • A total of 162 patients (pts) with intracranial GBM or GS tumors, following the completion of surgery (S) and radiotherapy (RT), participated in this multicenter, double-blind, placebo (PB)-controlled, parallel group study conducted in the US and Canada.
  • Time interval from time of diagnosis to start of Marimastat was about four months.
  • 79 pts were randomized to PB and 83 pts were randomized to receive Marimastat (MT) 10 mg po bid.
  • Pts who experienced disease progression could continue MT/PB with the addition of PCV chemotherapy if so desired; PCV was received by 15 PB- and 12 MT-treated pts.


  • Intention-to-treat analysis showed no statistically significant difference between MT and PB groups with respect to survival (p=O.38, log-rank test).
  • Median survival from protocol initiation was 9.1 months for the PB group and 10.3 months for the MT group.
  • There were also no statistically significant differences between PB and MT groups with respect to quality of life using the FACT-Br questionnaire.
  • The most common toxicity was Musculoskeletal (MS). Toxicities led to dose modification or withdrawal in 16 MT pts and only 1 PB pt. The onset of MS events was earlier with MT treatment (median 37 days) than with PB treatment (90 days), but it was delayed in those taking concomitant steroids.

Authors' Conclusions

    This study demonstrated that Marimastat did not improve survival in pts with GBM or GS who have completed surgery and RT.

Clinical/Scientific Implications:

    It would be interesting to see the tissue level changes that occur with Marimastat administration. In the future, imaging studies should allow us to better visualize the tissue level changes that occur with this agent. Of note, the time from diagnosis to the time of Marimastat administration appears prolonged in a disease with such an aggressive natural history. In further combination studies, this interval should be decrease if possible.

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