Phase I/Ib Clinical Trial of ABTL0812 in Advanced Cancer Patients

Cancer Clinical Trial

Official title:

A PHASE I/Ib, FIRST IN HUMAN, DOSE-ESCALATION STUDY OF ABTL0812 IN PATIENTS WITH ADVANCED SOLID TUMOURS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02201823
• Other study ID #: ABT-C1-2013
• Secondary ID: 2013-001293-17PE
• Status: Completed
• Phase: Phase 1
• First received: May 9, 2014
• Last updated: July 1, 2015
• Start date: February 2014
• Est. completion date: April 2015

Study information

• Verified date: July 2015
• Source: Ability Pharmaceuticals SL
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

Ability Pharmaceuticals promotes a clinical trial to determine the adequate dose of a new drug, ABTL0812, that will be administered orally daily to patients with advanced solid tumors.

Description:

This is a phase I/Ib, unicenter, open-label and single-agent study. This study consists of two different parts, a dose escalation phase and an extension phase in patients with advanced solid tumors.

ABTL0812 will be administered orally, daily, for 28 days (considered cycle 1). First endpoint is to determine the Maximum Tolerated Dose (MTD). MTD is defined as the highest dose at which no more than one in six patients experiences a ABTL0812 related Dose-Limiting Toxicity (DLT). DLT will be evaluated during the first treatment cycle.

Dose escalation phase will be performed with an accelerated design of 3 + 3

Once the 28 days cycle has finished, patients may continue receiving ABTL0812 on a daily continuous schedule if the patient is deemed to have clinical benefit from treatment, according to the treating physician. Treatment will continue until disease progression, onset of unacceptable drug toxicities, or patient/physician's request to discontinue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: April 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients older than 18 years of age

• Willing and able to provide informed consent

• Patients with histologically or cytologically confirmed diagnosis of advanced solid tumour refractory to standard treatment or for whom no effective therapy exists

• Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 guidelines

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

• All female subjects will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause), or have been sterilized surgically Female subjects of childbearing potential must agree to use two forms of highly effective contraception methods during the study and for a period of 6 months following the last administration of the study drug. Male subjects and their female partners who are of childbearing potential and are not practicing total abstinence, must agree to use two forms of highly effective contraception during the study and for a period of 6 months following the last administration of the study drug

• Adequate bone marrow function

• Adequate coagulation profile

• Adequate hepatic function

• Adequate renal function

• Life expectancy of at least 3 months, in the opinion of the investigator

• Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to = grade 1 (as defined by Common Terminology Criteria for Adverse Events version 4.02).

• Ability and willingness to comply with study visits, treatment, testing, and to comply with the protocol

Exclusion Criteria:

• Patients receiving treatment within 4 weeks prior to study entry with an investigational drug, chemotherapy, targeting agents or hormonal therapy (patients may continue to receive Luteinizing-hormone-releasing hormone analogue therapy for prostate cancer in face of rising PSA), radiation (except to bone) or surgery (except exploratory biopsy or intravenous device implantation, etc.) (6 weeks for nitrosoureas or Mitomycin C, or for investigational drug within 5 half-lives of the treatment, whichever is longer). Participation in non-interventional or observational studies is allowed.

• Patients with symptomatic brain metastases. Patients with asymptomatic brain metastases can be included in the study if they are kept on stable doses of steroids for a period of 1 month prior to study entry.

• Patients with gastrointestinal abnormalities including inability to take oral medications, malabsorption syndromes or other clinically significant gastrointestinal abnormalities that may impair the absorption of the investigational medicinal product.

• Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start.

• Patients with myocardial infarction within = 12 months prior to study entry, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina pectoris, or unstable cardiac arrhythmia requiring medication.

• Evidence of preexisting uncontrolled hypertension. Patients whose hypertension is controlled by antihypertensive therapies are eligible.

• Patients with known Hepatitis B or C or human immunodeficiency virus (HIV) infection

• Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that in the opinion of the investigator may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

Study Design

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

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• ABTL0812
ABTL0812. Five cohorts and one extension phase.

Locations

Country	Name	City	State
Spain	Hospital Clínic	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Ability Pharmaceuticals SL	Hospital Clinic of Barcelona, Institut Català d'Oncologia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluate the pharmacokinetic (PK) profile of ABTL0812 in patients with advanced solid tumours		First 28 days of treatment	No
Other	To evaluate the pharmacodynamic (PD) profile of ABTL0812 exploring preliminary biomarkers of drug activity		First 28 days of treatment	No
Primary	To determine the maximum tolerated dose (MTD) of ABTL0812, administered orally on a daily continuous schedule in adult patients with advanced solid tumours		First 28 days of treatment	Yes
Secondary	To assess safety and tolerability of ABTL0812		First 28 days of treatment	Yes
Secondary	To evaluate preliminary antitumour activity of ABTL0812		After 6 months of treatment	No
Secondary	To determine the recommended Phase II dose		First 28 days of treatment	No