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

NCT01182246 | Unknown Phase 1 DMC

• 1 other identifier: AXP-CT-001
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Adenocarcinoma

Keywords

adenocarcinoma; Pancreatic cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

  up to 6 months

Secondary Outcomes (10)

• To determine the pharmacokinetic (PK) profile of escalating doses of AXP107-11.

  Day -13, 1, 8 and 15

• To assess the safety and tolerability of a combination therapy of AXP107-11 and gemcitabine.

  up to 6 months

• To assess the effect of a combination therapy of AXP107-11 and gemcitabine on overall survival (OS).

  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.

  up to 6 months

• To assess the effect of a combination therapy of AXP107-11 and gemcitabine on time to progression (TTP).

  up to 6 months

Study Arms (1)

AXP107-11

EXPERIMENTAL

Drug: AXP107-11

Interventions

AXP107-11 DRUG

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.

Also known as: genistein

AXP107-11

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Axcentua Pharmaceuticals AB: lead

Study Sites (2)

Dept. of Clinical Science, Intervention and Technology, Div. of surgery, Karolinska University Hospital, Huddinge

Stockholm, SE-141 86, Sweden

RECRUITING

Dept. of Oncology-Pathology, Karolinska University Hospital, Solna

Stockholm, SE-17176, Sweden

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma; Pancreatic Neoplasms

Interventions

Genistein

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Isoflavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mattias Löhr, MD,PhD, Prof.

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2010
• First Posted: August 16, 2010
• Study Start: November 1, 2010
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

SE (2)