AXP107-11 in Combination With Standard Gemcitabine (Gemzar® ) Therapy for Treatment in Patients With Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Axcentua Pharmaceuticals AB
Sponsor:
Information provided by (Responsible Party):
Axcentua Pharmaceuticals AB
ClinicalTrials.gov Identifier:
NCT01182246
First received: August 4, 2010
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma
Drug: AXP107-11
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Axcentua Pharmaceuticals AB:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The tumour response evaluation will be performed according to RECIST (www.recist.org)


Secondary Outcome Measures:
  • To determine the pharmacokinetic (PK) profile of escalating doses of AXP107-11. [ Time Frame: Day -13, 1, 8 and 15 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • To assess the effect of a combination therapy of AXP107-11 and gemcitabine on time to progression (TTP). [ Time Frame: up to 6 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 44
Study Start Date: November 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AXP107-11 Drug: AXP107-11

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years at the time of signing the informed consent
  2. Histologically confirmed adenocarcinoma of the pancreas
  3. Metastatic or locally advanced, unresectable disease stage III-IV.
  4. Measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid tumors (RECIST) for target lesions
  5. Karnofsky Performance Status ≥ 70 at study entry (Appendix 18.4).
  6. Life expectancy of more than three months
  7. Negative pregnancy test for female patients
  8. For fertile women, willingness to perform double-barrier contraception during study and for four weeks after last treatment
  9. Able and willing to sign the informed consent form

Exclusion Criteria:

  1. Previous or ongoing severe supraventricular or ventricular arrhythmia
  2. Previous or ongoing coagulation or bleeding disorder (PTT > 1.5 x ULN)
  3. HIV infection
  4. Known hypersensitivity to any component of the AXP107-11 formulation or gemcitabine
  5. Previous or ongoing significant liver pathology (other than metastases) and/or liver function disorders
  6. Previous or ongoing significant chronic renal dysfunction
  7. Previous or ongoing malignancy other than pancreatic cancer < five years prior to enrolment, except basal cell carcinoma treated locally
  8. Cardiovascular disease, New York Heart Association (NYHA) classification III or IV16
  9. Severe pulmonary obstructive or restrictive disease
  10. Acute or chronic inflammation (autoimmune or infectious)
  11. Significant active/unstable non-malignant disease likely to interfere with study assessments
  12. 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
  13. Immunotherapy within six weeks prior to enrolment.
  14. Any chemotherapeutical treatment for pancreatic adenocarcinoma before enrolment
  15. Any radiotherapy for pancreatic adenocarcinoma before enrolment except for treatment of bone metastases if target lesions are not included in the irradiated field
  16. Major surgery within four weeks prior to enrolment
  17. Pregnant or nursing woman
  18. Participations in other interventional clinical study within four weeks of enrolment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01182246

Locations
Sweden
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    matthias.loehr@ki.se   
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    jan-erik.frodin@karolinksa.se   
Principal Investigator: Jan-Erik Frödin, MD         
Sponsors and Collaborators
Axcentua Pharmaceuticals AB
Investigators
Principal Investigator: Mattias Löhr, MD,PhD, Prof. Karolinska Institutet
  More Information

No publications provided

Responsible Party: Axcentua Pharmaceuticals AB
ClinicalTrials.gov Identifier: NCT01182246     History of Changes
Other Study ID Numbers: AXP-CT-001
Study First Received: August 4, 2010
Last Updated: April 22, 2014
Health Authority: Sweden: Medical Products Agency

Keywords provided by Axcentua Pharmaceuticals AB:
adenocarcinoma
Pancreatic cancer

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Genistein
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens

ClinicalTrials.gov processed this record on July 29, 2014