AdenocarcinomaPhase 1/2NCT01182246
AXP107-11 in Combination With Standard Gemcitabine (Gemzar® ) Therapy for Treatment in Patients With Pancreatic Cancer
A Phase 1/2 study testing AXP107-11 in people with Adenocarcinoma, run by Axcentua Pharmaceuticals AB at 2 sites in Sweden.
Trial summary
The purpose of this study is to assess the effect and safety of AXP107-11 alone, and in combination with gemcitabine standard therapy, in patients with advanced or metastatic cancer of the pancreas. The safety, pharmacokinetics and efficacy of AXP107-11 in these patients will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma
- What is being tested?
- AXP107-11
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 2 sitesSweden
- Study dates
- Nov 2010to Mar 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years at the time of signing the informed consent
- Histologically confirmed adenocarcinoma of the pancreas
- Metastatic or locally advanced, unresectable disease stage III-IV.
- Measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid tumors (RECIST) for target lesions
- Karnofsky Performance Status ≥ 70 at study entry (Appendix 18.4).
- Life expectancy of more than three months
Show all 9Show fewer
- Negative pregnancy test for female patients
- For fertile women, willingness to perform double-barrier contraception during study and for four weeks after last treatment
- Able and willing to sign the informed consent form
Who cannot join
- Previous or ongoing severe supraventricular or ventricular arrhythmia
- Previous or ongoing coagulation or bleeding disorder (PTT > 1.5 x ULN)
- HIV infection
- Known hypersensitivity to any component of the AXP107-11 formulation or gemcitabine
- Previous or ongoing significant liver pathology (other than metastases) and/or liver function disorders
- Previous or ongoing significant chronic renal dysfunction
Show all 27Show fewer
- Previous or ongoing malignancy other than pancreatic cancer < five years prior to enrolment, except basal cell carcinoma treated locally
- Cardiovascular disease, New York Heart Association (NYHA) classification III or IV16
- Severe pulmonary obstructive or restrictive disease
- Acute or chronic inflammation (autoimmune or infectious)
- Significant active/unstable non-malignant disease likely to interfere with study assessments
- Laboratory tests (hematology, chemistry) outside specified limits:
- WBC ≤ 3 x 10³/mm³
- ANC ≤ 1.5 x 10³/mm³
- Platelets ≤ 100.000/mm³
- Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l)
- PT/PTT > 1.5 x ULN
- Serum creatinine > 130 μmol/l) or clearance < 60 ml/min
- AST and/or ALT > 3 x ULN with the exception of patients with liver metastasis (> 5 x ULN)
- Alkaline phosphatase > 3 x ULN
- Total bilirubin > 3 x ULN
- Immunotherapy within six weeks prior to enrolment.
- Any chemotherapeutical treatment for pancreatic adenocarcinoma before enrolment
- Any radiotherapy for pancreatic adenocarcinoma before enrolment except for treatment of bone metastases if target lesions are not included in the irradiated field
- Major surgery within four weeks prior to enrolment
- Pregnant or nursing woman
- Participations in other interventional clinical study within four weeks of enrolment
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites, 2 recruiting
- Recruiting
Dept. of Clinical Science, Intervention and Technology, Div. of surgery, Karolinska University Hospital, Huddinge
Stockholm, SE-141 86
Matthias Löhr, +46 8 585 89591, matthias.loehr@ki.se
Mattias Löhr, MD, PhD,Prof.
- Recruiting
Dept. of Oncology-Pathology, Karolinska University Hospital, Solna
Stockholm, SE-17176
Jan-Erik Frödin, +46 8 517 733 89, jan-erik.frodin@karolinksa.se
Jan-Erik Frödin, MD
About this study
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
The purpose of this study is to assess the effect and safety of AXP107-11 alone, and in combination with gemcitabine standard therapy, in patients with advanced or metastatic cancer of the pancreas. The safety, pharmacokinetics and efficacy of AXP107-11 in these patients will also be studied.
Read the detailed description
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.
- Conditions
- Adenocarcinoma
- Being tested
- AXP107-11
- Keywords
- adenocarcinoma, Pancreatic cancer
- Medical subject headings
- Adenocarcinoma, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AXP107-11Drug
Also called genistein
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.
| Study group | Role | What they receive |
|---|---|---|
| AXP107-11 | Experimental | Not described Receives: Drug: AXP107-11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety profile and the maximum tolerated dose (MTD) of AXP107-11 alone and when given in combination with gemcitabine standard therapy.
Safety (AEs, dose limiting toxicity, laboratory tests, vital signs, weight and ECG). MTD is defined at day 8.
Measured: up to 6 months
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).
The tumour response evaluation will be performed according to RECIST (www.recist.org)
Measured: up to 6 months
Secondary outcomes (10)
To determine the pharmacokinetic (PK) profile of escalating doses of AXP107-11.
Plasma concentration of AXP107-11
Measured: Day -13, 1, 8 and 15
To assess the safety and tolerability of a combination therapy of AXP107-11 and gemcitabine.
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.
Measured: up to 6 months
To assess the effect of a combination therapy of AXP107-11 and gemcitabine on overall survival (OS).
Measured: 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.
Measured: up to 6 months
To assess the effect of a combination therapy of AXP107-11 and gemcitabine on time to progression (TTP).
Measured: 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).
The tumour response evaluation will be performed according to RECIST (www.recist.org)
Measured: up to 6 months
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.
Measured: 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).
Will be performed on the first 5 patients in the phase IIa part of the study.
Measured: up to 6 months
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).
Measured: 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.
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2010 (estimated)
- Study startNov 2010
- Primary completionMar 2016 (estimated)
- Study completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Axcentua Pharmaceuticals AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mattias Löhr, MD,PhD, Prof., Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01182246
- Sponsor's protocol ID
- AXP-CT-001
- Status last verified
- Apr 2014
- First submitted
- 4 Aug 2010
- Last updated
- 23 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01182246
- Acronym / sponsor ID
- AXP-CT-001
- Conditions
- Adenocarcinoma
- Keywords
- adenocarcinoma, Pancreatic cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Axcentua Pharmaceuticals ABIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Mar 2016 (estimated)
- Study completion
- Mar 2016 (estimated)
- First posted
- 16 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the effect and safety of AXP107-11 alone, and in combination with gemcitabine standard therapy, in patients with advanced or metastatic cancer of the pancreas. The safety, pharmacokinetics and efficacy of AXP107-11 in these patients will also be studied.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AXP107-11 | Experimental | Drug: AXP107-11 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age ≥ 18 years at the time of signing the informed consent
- Histologically confirmed adenocarcinoma of the pancreas
- Metastatic or locally advanced, unresectable disease stage III-IV.
- Measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid tumors (RECIST) for target lesions
- Karnofsky Performance Status ≥ 70 at study entry (Appendix 18.4).
Key exclusion criteria (27 listed)
- Previous or ongoing severe supraventricular or ventricular arrhythmia
- Previous or ongoing coagulation or bleeding disorder (PTT > 1.5 x ULN)
- HIV infection
- Known hypersensitivity to any component of the AXP107-11 formulation or gemcitabine
- Previous or ongoing significant liver pathology (other than metastases) and/or liver function disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AXP107-11Also: genisteinThe 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. | Drug | AXP107-11 |
Primary outcome
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)
10 secondary outcomes
To determine the pharmacokinetic (PK) profile of escalating doses of AXP107-11.
Time frame: Day -13, 1, 8 and 15
To assess the safety and tolerability of a combination therapy of AXP107-11 and gemcitabine.
Time frame: up to 6 months
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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
Related trials for Adenocarcinoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dept. of Clinical Science, Intervention and Technology, Div. of surgery, Karolinska University Hospital, Huddinge
Stockholm, Sweden
Dept. of Oncology-Pathology, Karolinska University Hospital, Solna
Stockholm, Sweden
Mattias Löhr, MD,PhD, Prof. principal investigator
Karolinska Institutet
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AXP107-11 in people with Adenocarcinoma, run by Axcentua Pharmaceuticals AB at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2014.