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A Randomized Phase 2 Study of ARQ 197 Versus Gemcitabine in Treatment-Naïve Patients With Unresectable Locally Advanced or Metastatic Pancreatic Adenocarcinoma

Phase 2
18 Years
Not Enrolling
Pancreatic Neoplasms

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Trial Information

A Randomized Phase 2 Study of ARQ 197 Versus Gemcitabine in Treatment-Naïve Patients With Unresectable Locally Advanced or Metastatic Pancreatic Adenocarcinoma

This is a multi-center, open-label randomized phase 2 study designed to evaluate the PFS of
treatment-naïve patients with unresectable (locally advanced or metastatic) pancreatic
adenocarcinoma following treatment with either ARQ 197 (ARQ arm) or gemcitabine alone (GEM
arm). The study will also evaluate other efficacy and safety parameters including ORR, OS
and adverse events in the two treatment arms. Patients randomly assigned to the GEM arm
will receive gemcitabine alone. Patients assigned to the ARQ arm will receive oral ARQ 197

ARQ 197 is an investigational oral drug supplied as capsules in multiple strengths. For the
study initial shipment the capsules were 120 mg each, 30 count. In the ARQ arm, patients
will take 120 mg of ARQ 197 twice daily, once in the morning and once in the evening one
hour prior to or two hours after a meal. ARQ 197 treatment will be continued until
unacceptable toxicity, documented progression of disease, or another discontinuation
criterion is met.

Gemcitabine is a commercially available drug for the treatment of patients with locally
advanced or metastatic adenocarcinoma of the pancreas. In the GEM arm, gemcitabine will be
administered by intravenous infusion over 30 minutes at a dose of 1000 mg/m2. The dosing
schedule of gemcitabine will be once weekly for the first cycle (4 weeks), then once weekly
for 3 consecutive weeks followed by a week of rest for each subsequent cycle. Gemcitabine
therapy will be continued until unacceptable toxicity, documented progression of disease, or
another discontinuation criterion is met.

A treatment cycle is defined as 28 days for both treatment arms. Cycles may be repeated
every 4 weeks (28 days) based on toxicity and response. The assigned treatment should
continue until unacceptable toxicity, disease progression (clinical or radiological) or
another discontinuation criterion is met.

Tumor evaluations: Tumor evaluations will be performed in 8-week intervals. Tumor response
(complete response, partial response, stable disease, progressive disease and ORR) will be
evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).

Progression-free survival: The time of disease progression-free will be calculated from
randomization until disease progression per RECIST or death due to any cause. Patients who
are alive and progression free will be censored at the date of their last tumor evaluation.

Overall survival: Overall survival time will be calculated from the date of randomization
until death due to any cause.

Safety assessments: Data on vital signs, physical examination, adverse events, serum
chemistry, hematological laboratory tests, and electrocardiograms will be collected.

This study is designed to establish potential efficacy of ARQ 197 in treatment naive
pancreatic cancer patients in a controlled, randomized study. The sample size of 30
Evaluable patients per treatment group is considered adequate to provide meaningful
estimates of the PFS and ORR and OS rates, however, this study is not powered to show
statistically significant differences between the treatment groups. Therefore, the analyses
will be primarily descriptive in nature. Taking into account an anticipated
drop-out/loss-to-follow-up rate of 20%, the total sample size will be 72 patients.

Primary and secondary objectives will be analyzed in the two treatment arms using
appropriate patient populations and statistical methods.

Inclusion Criteria:

1. Able to provide signed and dated informed consent prior to study-specific screening

2. ≥ 18 years old

3. Histologically or cytologically confirmed locally advanced or metastatic unresectable
pancreatic adenocarcinoma

4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors

5. Karnofsky performance status (KPS) ≥ 70%

6. Male or female patients of child-producing potential must agree to use double barrier
contraception, oral contraceptives or avoidance of pregnancy measures during the
study and for 90 days after the last day of treatment

7. Females of childbearing potential must have a negative serum pregnancy test

8. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × upper limit of
normal (ULN) or ≤ 5 × ULN with metastatic liver disease

9. Hemoglobin ≥ 10 g/dl

10. Total bilirubin ≤ 1.5 × ULN

11. Serum creatinine ≤ 1.5 x ULN

12. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L

13. Platelets ≥ 100 x 10^9/L

Exclusion Criteria:

1. 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)

2. Central nervous system metastases

3. Pregnant or breastfeeding

4. Significant gastrointestinal disorder, in the opinion of the Principal Investigator
(e.g. Crohn's disease, ulcerative colitis, extensive gastric resection)

5. Unable or unwilling to swallow ARQ 197 capsules twice daily

6. Other cancer within the last five years, with the exception of adequately treated
cone-biopsied in situ carcinoma of the cervix uteri or basal or squamous cell
carcinoma of the skin

7. Significant co-morbid conditions that in the opinion of the Investigator would impair
study participation

8. Known human immunodeficiency virus (HIV) or hepatitis C virus (HCV) infection

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluate progression-free survival (PFS) in patients receiving ARQ 197 versus gemcitabine.

Outcome Time Frame:

6 month

Safety Issue:


Principal Investigator

Cezary Szczylik, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Klinika Onkologii WIM


United States: Food and Drug Administration

Study ID:

ARQ 197-205



Start Date:

November 2007

Completion Date:

April 2008

Related Keywords:

  • Pancreatic Neoplasms
  • Pancreatic cancer
  • pancreas cancer
  • Locally advanced or metastatic pancreatic adenocarcioma
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Neoplasms
  • Pancreatic Neoplasms