AXP107-11 in Combination With Standard Gemcitabine (Gemzar® ) Therapy for Treatment in Patients With Pancreatic Cancer
|ClinicalTrials.gov Identifier: NCT01182246|
Recruitment Status : Unknown
Verified April 2014 by Axcentua Pharmaceuticals AB.
Recruitment status was: Recruiting
First Posted : August 16, 2010
Last Update Posted : April 23, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma||Drug: AXP107-11||Phase 1 Phase 2|
The annual incidence rate of pancreatic cancer is almost identical to the mortality rate. Despite a low incidence rate, pancreatic cancer is the fourth leading cause of cancer mortality in both men and women. Today is the only potentially curative option of these patients complete surgical resection. However, a majority of the patients (up to 80%) are not eligible for surgery for different reasons.
Today is gemcitabine the accepted first-line treatment for these patients. Recent advances in the management of pancreatic cancer suggest that gemcitabine may be improved by combining it with other anticancer drugs.
One attractive therapeutic option is genistein. Genistein appears to sensitize tumors to chemotherapy both by targeting the tumor cells and also by targeting components of the tumor microenvironment.
However, the limited bioavailability of genistein in its known crystalline form has led to difficulties in attaining adequate plasma concentration, resulting in limited application and dissemination in the clinical setting. To overcome this limitation, a novel crystalline form of genistein with improved pharmaceutical properties is being used. AXP107-11, a crystalline salt of genistein has improved physiochemical properties (solubility, dissolution rate, bioavailability) as compared to the known crystalline form of genistein.
In this study, AXP107-11, will be investigated alone and in combination with gemcitabine in patients with pancreatic cancer.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety, Pharmacokinetics and Efficacy of AXP107-11 in Combination With Standard Gemcitabine (Gemzar®) Treatment in Patients With Locally Advanced or Metastatic, Unresectable, Adenocarcinoma of the Pancreas, Stage III-IV: A Prospective, Open Label, Multi-centre, Sequential Phase Ib/IIa Study|
|Study Start Date :||November 2010|
|Estimated Primary Completion Date :||March 2016|
|Estimated Study Completion Date :||March 2016|
The drug substance, AXP107-11, is a crystalline form of genistein, a substance shown in literature data to target pancreatic tumor cells and also the tumor microenvironment and thus sensitizes tumors to chemotherapy. AXP107-11 is formulated in a capsule containing 2x100 mg of active substance.
A maximum of four cohorts of three to six patients each will be treated with escalating dose levels of AXP107-11 alone (two weeks) and in combination with gemcitabine (one week).
AXP107-11 capsules will be ingested orally twice daily (morning and evening) each day of the treatment period. In phase Ib, AXP107-11 will be administered once daily on the first treatment day (morning), followed by twice daily administrations continuously throughout the treatment period. When a minimum of six patients have been treated and evaluated on the maintenance dose (phase 1b), additional patients will be included directly into phase IIa.
Other Name: genistein
- Determine the safety profile and the maximum tolerated dose (MTD) of AXP107-11 alone and when given in combination with gemcitabine standard therapy. [ Time Frame: up to 6 months ]Safety (AEs, dose limiting toxicity, laboratory tests, vital signs, weight and ECG). MTD is defined at day 8.
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on objective response rate defined as the percentage of patients who showed complete response (CR) or partial response (PR). [ Time Frame: up to 6 months ]The tumour response evaluation will be performed according to RECIST (www.recist.org)
- To determine the pharmacokinetic (PK) profile of escalating doses of AXP107-11. [ Time Frame: Day -13, 1, 8 and 15 ]Plasma concentration of AXP107-11
- To assess the safety and tolerability of a combination therapy of AXP107-11 and gemcitabine. [ Time Frame: up to 6 months ]
Assessed by occurrence of adverse events, abnormal changes in laboratory parameters, vital signs, ECG, relevant patient withdrawal and percentage of patients having reduction, omission or discontinuation of any study medication.
Note: This is a secondary outcome measurement for patients in the phase IIa part of the study. This is a primary objective in phase Ib.
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on overall survival (OS). [ Time Frame: up to 6 months ]
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on overall survival rate at six months after start of combination therapy. [ Time Frame: up to 6 months ]
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on time to progression (TTP). [ Time Frame: up to 6 months ]
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on palliation, defined as the percentage of patients who showed CR, PR or stable disease (SD). [ Time Frame: up to 6 months ]The tumour response evaluation will be performed according to RECIST (www.recist.org)
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on clinical benefit response, a composite of measurements of pain (pain intensity and analgesics consumption), Karnofsky performance status and weight. [ Time Frame: up to 6 months ]
- To assess the effect of combination therapy of AXP107-11 and gemcitabine on the tumor mass using F-18 fluorodeoxyglucose positron emission tomography (FDG-PET). [ Time Frame: up to 6 months ]Will be performed on the first 5 patients in the phase IIa part of the study.
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on symptom distress score as measured by the Edmonton Symptom Assessment System (ESAS). [ Time Frame: up to 6 months ]
- To assess the effect of a combination therapy of AXP107-11 and gemcitabine on quality of life as assessed by the EORTC QLQ-C30 questionnaire and the PAN26 module. [ Time Frame: up to 6 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01182246
|Dept. of Clinical Science, Intervention and Technology, Div. of surgery, Karolinska University Hospital, Huddinge||Recruiting|
|Stockholm, Sweden, SE-141 86|
|Contact: Matthias Löhr +46 8 585 89591 email@example.com|
|Principal Investigator: Mattias Löhr, MD, PhD,Prof.|
|Dept. of Oncology-Pathology, Karolinska University Hospital, Solna||Recruiting|
|Stockholm, Sweden, SE-17176|
|Contact: Jan-Erik Frödin +46 8 517 733 89 firstname.lastname@example.org|
|Principal Investigator: Jan-Erik Frödin, MD|
|Principal Investigator:||Mattias Löhr, MD,PhD, Prof.||Karolinska Institutet|