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A Phase I Study of AR-67 (7-t-butyldimethylsilyl-10-hydroxycamptothecin) Given on Days 1, 4 8, 12 & 15 of an Every 21-day Cycle in Adult Patients With Refractory or Metastatic Solid Malignancies

Phase 1
18 Years
Not Enrolling
Solid Malignancies

Thank you

Trial Information

A Phase I Study of AR-67 (7-t-butyldimethylsilyl-10-hydroxycamptothecin) Given on Days 1, 4 8, 12 & 15 of an Every 21-day Cycle in Adult Patients With Refractory or Metastatic Solid Malignancies

Inclusion Criteria:

- Patients must be 18 years of age or greater and have a histologically or
cytologically proven solid malignancy that is metastatic or unresectable and for
which standard curative or palliative measures do not exist or are no longer
effective. Patients who have recurred after previous surgery and/or radiation may
participate in this trial, although no restriction is placed on the number of prior
therapies. Patients must be willing and able to have two core-needle biopsies of
their tumor to participate in this trial.

- Patients with known brain metastases are eligible for this clinical trial if their
disease has been treated and they are clinically stable (based on the assessment of
their treating physician) and documented by a stable or improved pretreatment CT or
MRI scan of the brain to evaluate for CNS disease within 28 days prior to

- Patients may have measurable OR non-measurable disease documented by CT, MRI, X-ray
or nuclear exam (FDG-PET). All disease must be assessed within 28 days prior to
registration. Pleural effusions, ascites and laboratory parameters are not
acceptable as the only evidence of measurable disease.

- Patients must have progressed after at least one prior chemotherapy and not be
candidates for salvage surgery. Prior biologic therapy or prior radiation is
permitted; however, at least two weeks must have elapsed since the completion of
prior therapy and patients must have recovered from all associated toxicities (due to
prior therapy) at the time of registration.

- At least three weeks must have elapsed since surgery (thoracic or other major
surgeries) and patients must have recovered from all associated toxicities at the
time of registration.

- Patients must have acceptable organ and marrow function documented within seven days
of registration and as defined below:

- Leukocytes >3,000/mcL

- Absolute neutrophil count >1,500/mcL

- Platelets >100,000/mcL

- Total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) <2.5 X institutional ULN

- Creatinine within normal institutional limits, OR

- Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal.

- Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of

- No other prior malignancy is allowed except for the following: adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
Stage I or II cancer from which the patient is currently in complete remission or
other cancer from which the patient has been disease-free for 3 years.

- Pregnant or nursing women may not participate in this trial because of the increased
risk of fetal harm including fetal death from the chemotherapeutic agents. In order
to participate in this trial, women / men of reproductive potential must agree to use
an effective contraceptive method (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation. Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately. Women of childbearing
potential must have a negative serum pregnancy test documented within seven days of

- Patients must be informed of the investigational nature of this study and must sign
and provide a written informed consent in accordance with institutional and federal

- Patients must have a life expectancy of greater than 12 weeks.

- Eligibility of patients receiving any medications or substances known to affect or
with the potential to affect the activity or pharmacokinetics of AR-67 will be
determined following review of their case by the Principal Investigator. Efforts
should be made to switch patients taking drugs that are strong inducers of the enzyme
CYP3A4 including anticonvulsants (i.e., phenytoin, phenobarbital, carbamazepine, or
primidone) and rifampin OR strong inhibitors of CYP3A4 (clarithromycin, itraconazole,
and ketoconazole) to other appropriate medications

Exclusion Criteria:

- Patients must not have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study.

- Patients may not be receiving any other investigational agents.

- 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.

- History of ≥ Grade 3 allergic reactions attributed to compounds of similar chemical
or biologic composition to AR-67 (i.e. camptothecins such as irinotecan, topotecan or
others of this class of pharmaceuticals).

- Patients with prior anaphylactic injection reaction of > Grade 3 to paclitaxel or any
other product formulated with Cremophor.

- Pregnant women are excluded from this study because AR-67 is a camptothecin with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with AR-67, breastfeeding should be discontinued if the mother is treated with

- HIV-associated symptoms may preclude accurate assessment of toxicity or response to
the treatment and because the primary endpoint of this Phase I trial is toxicity,
patients with HIV disease will be ineligible for participation. HIV-positive
patients on combination antiretroviral therapy are ineligible because of the
potential for pharmacokinetic interactions with AR-67. In addition, these patients
are at increased risk of lethal infections when treated with marrow-suppressive
therapy and are ineligible for enrollment on this study.

- Subjects with leukemia or primary brain tumors are excluded from this study.

- Subjects may not receive any of the following medications two weeks prior to, during
or two weeks after initiation of AR-67: aprepitant, atazanavir, bacillus of Calmette
and Guerin vaccine, carbamazepine, citalopram, ketoconazole, intraconazole, measles
virus vaccine, mumps virus vaccine, phenobarbital, phenytoin, poliovirus vaccine,
rifabutin, rifampin, rotavirus vaccine, rubella virus vaccine, smallpox vaccine, St
John's wort, typhoid vaccine, varicella virus vaccine or yellow fever vaccine.

Type of Study:


Study Design:

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

Outcome Measure:

To evaluate the feasibility of obtaining two serial tumor biopsies and plasma pharmacokinetics for the determination of AR-67 half life in tumor and plasma during day 1 of AR-67 treatment given on days 1, 4, 8, 12 and 15 of an every 21-day cycle.

Outcome Time Frame:

Cycle 1 days 1 and 2

Safety Issue:


Principal Investigator

Susanne M Arnold, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Lucille P. Markey Cancer Center at University of Kentucky


United States: Food and Drug Administration

Study ID:




Start Date:

September 2010

Completion Date:

July 2011

Related Keywords:

  • Solid Malignancies
  • Cancer
  • Tumors
  • Neoplasms



Markey Cancer Center, University of Kentucky Lexington, Kentucky  40536