Phase II Randomized, Open-Label, Multicenter Study Comparing CO-1.01 With Gemcitabine as First-Line Therapy in Patients with Metastatic Pancreatic Adenocarcinoma
- Conditions
- Gemetastaseerd pancreatisch adenocarcinoom (stadium 4).Metastatic pancreatic adenocarcinoma. Pancreatic cancer.
- Registration Number
- NL-OMON36550
- Lead Sponsor
- Clovis Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
* Metastatic pancreatic adenocarcinoma (i.e., Stage 4).
* Histological/cytological confirmation of metastatic tissue (not primary tumor) by a
central pathology laboratory (H&E stain) to ensure sufficient material is available for
later hENT1 analysis.
* Biopsy from metastases must be obtained *3 months after adjuvant
chemotherapy (if applicable).
* Paraffin block sufficient for preparing *6 unstained slides for central storage and
subsequent hENT1 analysis is required.
* Adjuvant chemotherapy/radiotherapy *6 months prior to randomization.
* Palliative radiotherapy (if administered) *1 month prior to randomization.
* CT scan *30 days prior to randomization.
* Performance Status (ECOG) 0 or 1.
* Estimated life expectancy *12 weeks.
* Age *18 years.
* Adequate hematological and biological function, defined as the following changes in
the central laboratory values:
Bone marrow function
* Neutrophils *1.5 × 109/L
* Platelets >100.0 × 109/L
* Hemoglobin *10 g/dL
Hepatic function
* AST *2.5 × upper limit of normal (ULN); if liver metastases, *5 × ULN
* Bilirubin *1.5 times ULN; if liver metastases, *3 × ULN
* Albumin >3 g/dL
* PT/PTT within 10% ULN
Renal function
* Serum creatinine *1.5 × ULN
* Written consent on an IRB/IEC-approved Informed Consent Form prior to any
study-specific evaluation.
* Prior palliative chemotherapy for pancreatic cancer.
* Radical pancreatic resections (e.g., Whipple procedure) are not allowed < 6 months
prior to randomization. Exploratory laparotomy, palliative (e.g., bypass) surgery, or
other procedures (e.g., stents) are not allowed <14 days prior to randomization. In
both cases the patient must be sufficiently recovered and stable.
* Symptomatic brain metastases.
* Participation in other investigational drug clinical studies *30 days prior to
randomization.
* Concomitant treatment with prohibited medications (e.g., concurrent anticancer
therapy including other chemotherapy, radiation, hormonal treatment, or
immunotherapy) *30 days prior to randomization.
* QTcF > 450 msec (male) or > 470 msec (female).
* History of allergy to gemcitabine or eggs.
* Presence of any serious or unstable concomitant systemic disorder incompatible with
the clinical study (e.g., substance abuse, uncontrolled intercurrent illness including
active infection, arterial thrombosis, symptomatic pulmonary embolism).
* Significant neurological or psychiatric disorder that would hamper protocol
compliance.
* Prior nonpancreatic malignancy treated with chemotherapy. Prior malignancies
treated with surgery or radiotherapy alone must be in remission *3 years. Prior
malignancies allowed irrespective of when they occurred are in situ carcinoma of the
cervix, in situ ductal breast cancer, low-grade local bladder cancer, and nonmelanotic
skin cancer.
* Females who are pregnant or breastfeeding.
* Refusal to use adequate contraception (Section 6.3) for fertile patients (females and
males for 6 months after the last protocol-specified treatment).
* Any other reason the investigator considers the patient should not participate in the
study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall survival in patients with low hENT1 expression.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* OS in all patients and patients with high hENT1 expression<br /><br>* Objective tumor response rate (ORR), duration of response, and<br /><br>progression-free<br /><br>survival (PFS) in patients with measurable/evaluable disease using RECIST 1.1<br /><br>* CA 19-9 response rate<br /><br>* Drug tolerability and toxicity using clinical AE monitoring, clinical<br /><br>laboratory<br /><br>testing, ECG outcomes, and dose modifications of protocol-specified treatment<br /><br>* Change from baseline in pain severity measured by the worst pain on the BPI<br /><br>short<br /><br>form<br /><br>* Change from baseline in health status measured by the EQ-5D instrument and EQ<br /><br>VAS<br /><br>* PK profiles for CO-1.01and gemcitabine (substudy only) correlated with ECG<br /><br>changes (especially QTc interval)</p><br>