Study to Evaluate Efficacy of CO-1.01 as Second Line Therapy for Gemcitabine-Refractory Stage IV Pancreatic Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01233375
Recruitment Status : Completed
First Posted : November 3, 2010
Last Update Posted : December 31, 2014
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Brief Summary:
The purpose of this study is to determine whether CO-1.01 is safe and effective for treating metastatic pancreatic cancer that did not respond to gemcitabine.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: CO-1.01 Phase 2

Detailed Description:
Pancreatic tumors with low hENT1 expression may show less benefit from gemcitabine compared with those with higher expression of this nucleoside transporter. Nonclinical studies indicate that CO-1.01, a gemcitabine derivative, is effective independent of such transporters. Thus patients with low or no meaningful expression of hENT1 who failed to respond to gemcitabine might derive benefit from CO1.01 before needing alternative (combination) chemotherapy. Furthermore, the PK profiles of CO-1.01 and gemcitabine are dissimilar and this may confer additional clinical benefit on CO1.01.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Multicenter Study to Evaluate the Antitumor Efficacy of CO-1.01 for Infusion as Second-Line Therapy for Gemcitabine- Refractory Patients With Stage IV Pancreatic Adenocarcinoma and No Tumor hENT1 Expression
Study Start Date : April 2011
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine

Arm Intervention/treatment
Experimental: CO-1.01 Drug: CO-1.01

1250 mg/m2/day administered on Days 1, 8, and 15 in 4-week treatment cycles.

Patients who have SD or better at the Week 8 assessment and who adequately tolerated the first 2 cycles of treatment may continue CO-1.01 at the same or an increased dose (1400 mg/m2) for Cycle 3 and subsequent cycles.

Primary Outcome Measures :
  1. Disease Control Rate (CR, PR, or SD) using RECIST 1.1 [ Time Frame: Every 8 weeks until disease progression ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Every 8 weeks ]
  2. CA 19-9 response rate [ Time Frame: Every 4 weeks ]
  3. Progression-free survival (PFS) [ Time Frame: Every 8 weeks ]
  4. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Every week ]
  5. Overall survival (OS) [ Time Frame: 3, 6, 9, and 12 months ]
  6. Median progression-free survival [ Time Frame: 3, 6, 9, and 12 months ]
  7. Median overall survival [ Time Frame: 3, 6, 9, and 12 months ]
  8. Duration of response [ Time Frame: Every 8 weeks ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Gemcitabine-refractory metastatic ductal adenocarcinoma of the pancreas

    • At least 1 measurable lesion according to RECIST 1.1 criteria
    • Computerized tomography (CT) scan ≤ 28 days prior to CO-1.01
    • First-line treatment included at least 3 doses of gemcitabine (as monotherapy or combination therapy) with the last dose administered at least 2 weeks prior to CO 1.01
    • Radiological best response of disease progression after 1st-line treatment (no radiological stable disease or better allowed at any time)
    • Patients who experienced progressive disease during (neo)-adjuvant gemcitabine-based therapy are also eligible
    • Patients who have completed previous adjuvant therapy without progression, then subsequently have a radiological best response of disease progression on 1st line gemcitabine for metastatic disease are eligible
  2. No hENT1 expression in primary or metastatic tumor sample, confirmed with IHC by a core pathology laboratory prior to study entry also eligible
  3. Performance Status (ECOG) 0 or 1
  4. Age ≥18 years
  5. Palliative radiotherapy (if administered) ≥2 weeks prior to CO-1.01
  6. Adequate hematological and biological function, with no residual gemcitabine-related toxicity
  7. Written consent on an Institutional Review Board (IRB)-approved IC Form prior to any study-specific evaluation

Exclusion Criteria:

  1. Patients who have had stable disease, partial response or complete response to first line gemcitabine-based therapy
  2. First-line chemotherapy regimen that does not contain gemcitabine
  3. First-line treatment discontinued due to intolerable gemcitabine-induced toxicity
  4. Second or subsequent line therapy for advanced disease. Prior exposure to CO-1.01 or prior randomization in a protocol studying CO-1.01 (e.g.,Protocol CO-101-001)
  5. Tumor that cannot be evaluated for hENT1 expression or that has hENT1 staining in >50% of cells
  6. Symptomatic brain metastases
  7. Concomitant treatment with prohibited medications (e.g., concurrent anticancer therapy including other chemotherapy, radiation, hormonal treatment [except corticosteroids and megestrol acetate], or immunotherapy) ≤14 days prior to CO-1.01
  8. Exploratory laparotomy, palliative (e.g., bypass) surgery, or other procedures are not allowed <14 days prior to CO-1.01 administration; stenting procedures are permissible at any time prior to dosing; in all cases, the patient must be sufficiently recovered and stable
  9. History of allergy to gemcitabine or eggs
  10. Females who are pregnant or breastfeeding
  11. Refusal to use adequate contraception for fertile patients (females and males during the study and for 6 months after the last dose of CO-1.01)
  12. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including active infection, arterial thrombosis, or symptomatic pulmonary embolism)
  13. Any other reason for which the investigator considers the patient should not participate in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01233375

United States, Arizona
Arizona Cancer Center at University of Arizona
Tucson, Arizona, United States, 85724
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
Palm Beach Institute / Collaborative Research Group
Boynton Beach, Florida, United States, 33425
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Piedmont Healthcare Research Institute (PHRI)
Atlanta, Georgia, United States, 30309
United States, Kentucky
Norton Cancer Institute Research Program
Louisville, Kentucky, United States, 40202
United States, Maryland
Johns Hopkins Oncology Center
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital (MGH)
Boston, Massachusetts, United States, 02114
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Columbia University Medical Center, Milstein Hospital
New York, New York, United States, 10032
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232-1305
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Clovis Oncology, Inc.
Principal Investigator: Eileen O'Reilly, M.D. Memorial Sloan Kettering Cancer Center

Responsible Party: Clovis Oncology, Inc. Identifier: NCT01233375     History of Changes
Other Study ID Numbers: CO-101-003
First Posted: November 3, 2010    Key Record Dates
Last Update Posted: December 31, 2014
Last Verified: December 2014

Keywords provided by Clovis Oncology, Inc.:
human equilibrative nucleoside transporter-1 (hENT1)
Stage 4
Stage IV
Second-Line Therapy

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs