The study is divided into two parts. The first part, Phase Ib, is designed to evaluate the safety and tolerability of ARQ 501 in combination with gemcitabine in adult patients with solid malignancies. The result of this part of the study will be to define a combination regimen for the second part of the study. The second part of the study, Phase II, will document the safety and efficacy of the combination of ARQ 501 and gemcitabine in patients with unresected, pancreatic cancer.

Condition	Treatment or Intervention	Phase
Pancreatic Cancer Adenocarcinoma	Drug: ARQ 501 in combination with gemcitabine	Phase I Phase II

Further Study Details: 

Primary Outcomes: Phase Ib: Define a maximum tolerated dose of ARQ 501 in combination with gemcitabine; Phase II: Document progression free survival after treatment with ARQ 501 and gemcitabine
Secondary Outcomes: Phase Ib: Safety and tolerability of ARQ 501 in combination with gemcitabine; Phase II: Document safety and efficacy of ARQ 501 in combination with gemcitabine
Expected Total Enrollment:  87

This is a Phase Ib/II study of ARQ 501 in combination with gemcitabine in adult patients with solid malignancies (Phase Ib) or with metastatic pancreatic adenocarcinoma (Phase II).

Phase Ib

Phase Ib is an open-label, single-arm, non-randomized, dose-escalating study of ARQ 501 in combination with gemcitabine in adult patients with solid malignancies. The study objectives are as follows:

Primary Objective:

• To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of ARQ 501 in combination with gemcitabine in adult patients with solid malignancies.

Secondary Objectives:

• To determine the safety profile and tolerability of ARQ 501 in combination with gemcitabine;
• To determine the pharmacokinetic profile of ARQ 501 in combination with gemcitabine
• To collect information about the antitumor effects of ARQ 501 when administered in combination with gemcitabine.

Phase II

Phase II is a single-arm, non-randomized study of ARQ 501 in combination with gemcitabine in adult patients with treatment-naïve, unresectable, metastatic pancreatic adenocarcinoma. The study objectives are as follows:

Primary Objective:

• To document the progression-free survival (PFS) following treatment with ARQ 501 in combination with gemcitabine in adult patients with treatment-naïve, unresectable, metastatic pancreatic adenocarcinoma.

Secondary Objectives:

• To document the overall survival (OS) at 12 months following treatment with ARQ 501 in combination with gemcitabine;
• To document the tumor response to treatment with ARQ 501 in combination with gemcitabine;
• To monitor the pharmacokinetic profile of ARQ 501 in combination with gemcitabine

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Phase Ib

Inclusion Criteria:

• Have a histologically or cytologically confirmed diagnosis of a solid malignancy. (Patients may have either measurable or nonmeasurable disease.)
• Be ≥18 years old.
• Must not be eligible for therapy of higher curative potential. (Where an alternative therapy has been shown to prolong survival in an analogous population, that therapy will be offered to the patient prior to discussing this study.)
• Have a Karnofsky Performance Status (KPS) of ≥70%.
• Have an estimated life expectancy of ≥12 weeks.
• Be male or a non-pregnant, non-lactating female patient. Patients who are fertile agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, or cervical cap) to avoid pregnancy.
• Have a negative serum or urine pregnancy test within 7 days prior to the first dose of study drug (if patient is a female of childbearing potential).
• Sign a written informed consent document.
• Have adequate organ function as indicated by acceptable laboratory values obtained within 7 days prior to the first dose of study drug.

Exclusion Criteria:

• Have received previous treatment with ARQ 501.
• Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
• Are pregnant or lactating.
• Have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.
• Have received any chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational, within 2 weeks of treatment in this study.
• Have not recovered from acute toxicity of all previous therapy prior to enrollment.
• Have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Have symptomatic or untreated central nervous system (CNS) metastases.
• Have a known hypersensitivity to gemcitabine.

Phase II

Inclusion Criteria:

• Have a pathologically confirmed diagnosis of unresectable, metastatic pancreatic adenocarcinoma
• Be treatment-naïve.
• Have measurable disease per RECIST Criteria.
• Be ≥18 years old.
• Have a Karnofsky Performance Status (KPS) of ≥70%.
• Have an estimated life expectancy of ≥12 weeks.
• Be male or a non-pregnant, non-lactating female patient. Patients who are fertile agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, or cervical cap) to avoid pregnancy.
• Have a negative serum or urine pregnancy test within 7 days prior to the first dose of study drug (if patient is a female of childbearing potential).
• Sign a written informed consent form.
• Have adequate organ function as indicated by acceptable laboratory values obtained within 7 days prior to the first dose of study drug.

Exclusion Criteria:

• Have received any prior therapy for the treatment of their pancreatic malignancy (including chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational).
• Have an active, uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment.
• Are pregnant or lactating.
• Have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.
• Have any other severe concurrent disease, which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• Have symptomatic or untreated central nervous system (CNS) metastases.
• Have a known hypersensitivity to gemcitabine.

Amanda Ferrier, RN      781.994.0300    aferrier@arqule.com
Deb Pesik, RN      781.994.0300    dpesik@arqule.com

Texas
      MD Anderson Cancer Center, Houston,  Texas,  United States; Recruiting

Study ID Numbers:  ARQ 501-212
Record last reviewed:  March 2005
Last Updated:  March 16, 2005
Record first received:  February 1, 2005
ClinicalTrials.gov Identifier:  NCT00102700
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08