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

NCT ID: NCT01233375

Last Updated: 2019-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-03-31

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.

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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CO-1.01

Group Type: EXPERIMENTAL

CO-1.01

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clovis Oncology, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eileen O'Reilly, M.D.

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Arizona Cancer Center at University of Arizona

Tucson, Arizona, United States

Rocky Mountain Cancer Center

Denver, Colorado, United States

Palm Beach Institute / Collaborative Research Group

Boynton Beach, Florida, United States

University of Miami

Miami, Florida, United States

Piedmont Healthcare Research Institute (PHRI)

Atlanta, Georgia, United States

Norton Cancer Institute Research Program

Louisville, Kentucky, United States

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Massachusetts General Hospital (MGH)

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Columbia University Medical Center, Milstein Hospital

New York, New York, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

CO-101-003

Identifier Type: -

Identifier Source: org_study_id