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A Phase I Study of IPI-504 and Docetaxel in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Solid Tumors

Thank you

Trial Information

A Phase I Study of IPI-504 and Docetaxel in Patients With Advanced Solid Tumors

IPI-504 is a novel small molecule inhibitor of heat shock protein 90 (Hsp90), an emerging
and recently identified target for cancer therapy. Hsp90 is a protein chaperone that plays a
central role in maintaining the proper folding, function and viability of various "client
proteins". Many of the client proteins stabilized by Hsp90 are oncoproteins and
cell-signaling proteins important in cancer cell proliferation and cancer cell survival.

This is a multi-center, open-label, dose escalating study in which patients will be treated
with a fixed dose of docetaxel followed by IPI-504 following one of three dosing schedules.

Once an MTD has been defined, up to 20 additional patients with non-small cell lung cancer
(NSCLC) will be enrolled.

Inclusion Criteria:

- Pathologically confirmed malignancy that is metastatic or unresectable, for which one
of the two statements must apply:

- Standard therapy able to provide clinical benefit does not exist or is no
longer effective AND / OR

- Single agent docetaxel would be appropriate therapy.

- Progressive disease with development of new lesions or an increase in preexisting
lesions on CT, MRI, PET, bone scintigraphy, or by physical examination.

- Measurable disease by RECIST criteria with the exception of prostate cancer patients.

- >18 years of age at the time of signing the Informed Consent Form (ICF) and have a
life expectancy of at least 3 months.

- Karnofsky performance status of 70 or better.

- Adhere to the study visit schedule

- Voluntarily sign the Informed Consent Form (ICF).

- Baseline studies completed within 30 days of first study dose.

- Women of child-bearing potential (WCBP) defined as a sexually mature woman who has
not undergone a hysterectomy or who has not been naturally post-menopausal for at
least 24 consecutive months must have a negative serum or urine pregnancy test within
2 weeks of first study dose and prior to each additional cycle of treatment.

- All WCBP and all sexually active male patients must agree to use adequate methods of
birth control throughout the study

** Non-small cell lung cancer (NSCLC)enrolled in the Expansion Phase of the study
must meet the following additional inclusion criteria:

- NSCLC that meets the disease criteria described in the first three Inclusion

- Must have archival NSCLC tissue available for submission and analysis.

Exclusion Criteria:

- Treatment within 1 week of the start of IPI-504 for erlotinib, and imatinib; within 2
weeks for gefitinib, and any other tyrosine kinase inhibitor (approved or
investigational); within 4 weeks for any biologic therapy (antibody, vaccine, or
other protein-based therapy), radiation therapy, or conventional chemotherapy; within
6 weeks for nitrosoureas or mitomycin C.

- Radiation therapy within 2 weeks of the start of IPI-504. (Patients must have
recovered from any toxicities.)

- Concurrent radiation therapy or treatment with any other investigational agent is not

- Use of a medication or food that is a clinically relevant CYP3A inhibitor or inducer
within 2 weeks prior to Cycle 1, Dose 1.

- Symptomatic peripheral neuropathy ≥ Grade 2.

- Inadequate hematologic function defined by absolute neutrophil count (ANC) <1,500
cells/mm3, a platelet count <100,000/mm3, and a hemoglobin <9.0 g/dL (may be
increased to this level with transfusion as long as there is no evidence of active

- Inadequate renal function defined by AST and/or ALT >1.5; total bilirubin above the
upper limit of normal.

- Inadequate renal function defined by serum creatinine >1.5 x ULN.

- Sinus bradycardia (resting heart rate <50) secondary to intrinsic conduction system
disease. Patients with sinus bradycardia secondary to pharmacologic treatment may
enroll if withdrawal of the treatment results in normalization of the resting heart
rate to within normal limits.

- Baseline QTc >450 msec in males; QTc >470 msec in females, or previous history of QT
prolongation while taking other medications.

- Presence of left bundle branch block, right bundle branch block plus left anterior
hemiblock, bifasicular block or 3rd degree heart block. This does not include
patients with a history of these events with adequate control by pacemaker.

- Patients who have received >450 mg/m2 of any anthracycline during prior chemotherapy
must have a baseline LVEF >40%.

- Active keratitis or keratoconjunctivitis.

- History of severe hypersensitivity reaction to docetaxel or other drugs formulated
with polysorbate 80.

- Presence of active infection or systemic use of antibiotics within 72 hours of

- Untreated brain metastases. Note: Patients with a history of brain metastases are
eligible as long as definitive treatment has been given and patients are clinically

- Significant co-morbid condition or disease which in the judgment of the Investigator
would place the patient at undue risk or interfere with the study (e.g., cardiac
disease such as acute coronary syndrome or unstable angina within 6 months,
uncontrolled hypertension, arrhythmia requiring medication or mechanical control,
cirrhotic liver disease, or other conditions).

- Previous or current malignancies at other sites within the last 2 years, with
exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri
and basal or squamous cell carcinoma of the skin.

- HIV-positive patients receiving combination antiretroviral therapy.

- Women who are pregnant or lactating.

- Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor.

- Patients with prior hepatic resection or hepatic-directed therapy (e.g.,
chemoembolization or Theresphere).

**Patients with non-small cell lung cancer (NSCLC)enrolled in the Expansion Phase of
the study must meet the following additional exclusion criteria:

- Prior treatment with docetaxel

- Three or more chemotherapy regimens for metastatic disease. Note: Any number of
prior treatment regimens with tyrosine kinase inhibitors is permitted.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety, maximum tolerated dose(MTD)of IPI-504 in combination with docetaxel in patients with advanced solid tumors and recommend the Phase II dose of the combination of drugs.

Outcome Time Frame:


Safety Issue:


Principal Investigator

Gregory Riely, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2007

Completion Date:

December 2011

Related Keywords:

  • Solid Tumors
  • Solid Tumors, IPI-504, docetaxel,cancer
  • Neoplasms



Roswell Park Cancer InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Yale Cancer CenterNew Haven, Connecticut  06520-8028
University of Pittsburgh Medical CenterPittsburgh, Pennsylvania  15213
H. Lee Moffitt Cancer Center & Research InstituteTampa, Florida  33612
Gabrail Cancer CenterCanton, Ohio  44718
TGen Clinical Research in ScottsdaleScottsdale, Arizona  85258