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

Phase 2

Completed

Conditions: Metastatic Pancreatic Adenocarcinoma

Interventions: Drug: CO-1.01

Registration Number: NCT01233375

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

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
No hENT1 expression in primary or metastatic tumor sample, confirmed with IHC by a core pathology laboratory prior to study entry also eligible
Performance Status (ECOG) 0 or 1
Age ≥18 years
Palliative radiotherapy (if administered) ≥2 weeks prior to CO-1.01
Adequate hematological and biological function, with no residual gemcitabine-related toxicity
Written consent on an Institutional Review Board (IRB)-approved IC Form prior to any study-specific evaluation

Exclusion Criteria

Patients who have had stable disease, partial response or complete response to first line gemcitabine-based therapy
First-line chemotherapy regimen that does not contain gemcitabine
First-line treatment discontinued due to intolerable gemcitabine-induced toxicity
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)
Tumor that cannot be evaluated for hENT1 expression or that has hENT1 staining in >50% of cells
Symptomatic brain metastases
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
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
History of allergy to gemcitabine or eggs
Females who are pregnant or breastfeeding
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)
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)
Any other reason for which the investigator considers the patient should not participate in the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CO-1.01	CO-1.01	-

Primary Outcome Measures

Name	Time	Method
Disease Control Rate (CR, PR, or SD) using RECIST 1.1	Every 8 weeks until disease progression

Secondary Outcome Measures

Name	Time	Method
Median overall survival	3, 6, 9, and 12 months
Overall Response Rate (ORR)	Every 8 weeks
CA 19-9 response rate	Every 4 weeks
Progression-free survival (PFS)	Every 8 weeks
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Every week
Overall survival (OS)	3, 6, 9, and 12 months
Median progression-free survival	3, 6, 9, and 12 months
Duration of response	Every 8 weeks

Trial Locations

Locations (13): Piedmont Healthcare Research Institute (PHRI)
🇺🇸
Atlanta, Georgia, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of Miami
🇺🇸
Miami, Florida, United States
Norton Cancer Institute Research Program
🇺🇸
Louisville, Kentucky, United States
Arizona Cancer Center at University of Arizona
🇺🇸
Tucson, Arizona, United States
Palm Beach Institute / Collaborative Research Group
🇺🇸
Boynton Beach, Florida, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Johns Hopkins Oncology Center
🇺🇸
Baltimore, Maryland, United States
Rocky Mountain Cancer Center
🇺🇸
Denver, Colorado, 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
Massachusetts General Hospital (MGH)
🇺🇸
Boston, Massachusetts, United States
University of Pittsburgh Cancer Institute
🇺🇸
Pittsburgh, Pennsylvania, United States