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Phase I/II Study of PCI-24781 in Combination With Doxorubicin for Treatment of Advanced Sarcomas Following Failure or Prior Anthracycline Therapy

Phase 1/Phase 2
18 Years
Open (Enrolling)

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Trial Information

Phase I/II Study of PCI-24781 in Combination With Doxorubicin for Treatment of Advanced Sarcomas Following Failure or Prior Anthracycline Therapy

- In the phase I portion of the study, since we are looking for the highest dose of
PCI-24781 that can be administered safely without severe or unmanageable side effects
in participants that have advanced sarcoma, not everyone who participates in this
research study will receive the same dose of PCI-24871.

- Each treatment cycle is 3 weeks (21 days). Participants will take capsules of
PCI-24871 for five consecutive days starting on Day 1 of each 3 week cycle. On Day 4
of each cycle, participants will come to the clinic to receive doxorubicin

- At specific time intervals, participants will return to the clinic for the following
tests and procedures: physical examination, vital signs, blood tests, urine test, EKG,
assessment of the tumor by CT scan, and an ECHO or MUGA.

- Participants may remain on the study for a maximum of 6 cycles (about 4-5 months).
After the last cycle, as long as the participant is showing benefit, they may elect to
continue taking PCI-24781 alone, in which case they will continue in this research
study until there is evidence of their tumor growing.

Inclusion Criteria:

- Participants must have histologically confirmed metastatic or unresectable sarcoma

- All participants must have received no more than a lifetime cumulative maximum dose
of 300 mg/m2 or less of prior doxorubicin and no other anthracycline therapy.

- Participants must have measurable disease, defined as at least one unirradiated
lesion that can be accurately measured in at least one dimension as 20mm or greater
with conventional techniques or as 10mm or greater with spiral CT scan.

- ECOG performance status of 2 or less

- Ability to swallow oral capsules without difficulty

- Participants must have normal organ and marrow function as outlined in the protocol.

- Women of childbearing potential must have a negative serum/urine pregnancy test
within 7 days prior to receiving the first dose of PCI-24781.

- An ECHO or MUGA demonstrating EF > 50% is required within 4 weeks prior to study drug

- 18 years of age or older

Exclusion Criteria:

- Participants who have had immunotherapy, chemotherapy, experimental therapy or
radiotherapy within 4 weeks before first day of study drug dosing or those who have
not recovered to grade 1 or baseline from adverse events due to agents administered
more than 4 weeks earlier.

- Participants who have previously received > 300 mg/m2 cumulative lifetime dose of
doxorubicin, or who have received any other anthracycline chemotherapy.

- Major surgery within 4 weeks before first day of study drug dosing

- Participants with known central nervous system/brain metastases

- Participants receiving chronic corticosteroids > 20 mg prednisone equivalent per day
for > 7 consecutive days (Topical, inhaled or nasal corticosteroids are permitted).

- Participants with any documented malabsorption syndromes or other conditions that may
impair the absorption of PCI-24781 capsules.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Participants requiring concurrent therapeutic anticoagulation or have received
therapeutic anticoagulation within 2 weeks of the first day of dosing.

- Risk factors for Torsades de Pointes, or use, within 4 weeks of starting study drug
administration, of medications known to prolong QTc interval or that may be
associated with Torsades de Pointes.

- QTc prolongation or other significant ECG abnormalities defined as 2nd degree AV
block type II, 3rd degree AV block, or bradycardia.

- History of myocardial infarction, acute coronary syndromes, coronary angioplasty
and/or coronary artery stenting within the past 6 months.

- For patients with history of major coronary artery disease in the judgement of the
responsible physician, a cardiac stress test that demonstrates clinically significant
abnormalities when performed within 28 days of first dose of study drug

- Pregnant or breastfeeding women

- Women of childbearing potential, or sexually active men unwilling to use adequate
contraceptive protection during the course of the study

- HIV-positive individuals

- Other medical or psychiatric illness or organ dysfunction that, in the opinion of the
investigator, would either compromise the patient's safety or interfere with the
evaluation of the safety of PCI-24781

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I: To determine the MTD (and/or recommended phase II dose) of PCI-24781 when given orally twice a daily for 5 days in combination with doxorubicin.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Edwin Choy, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

February 2009

Completion Date:

December 2013

Related Keywords:

  • Sarcoma
  • PCI-24781
  • doxorubicin
  • Sarcoma



Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Massachusetts General HospitalBoston, Massachusetts  02114-2617