A phase I/ II study to assess the efficacy and safety of ABTL0812 in combination with paclitaxel and carboplatin in patients with advanced endometrial cancer or squamous NSCLC

Phase 1

• Conditions: Squamous Cell Non-Small Cell Lung Cancerandadvanced endometrial cancer; MedDRA version: 19.0Level: PTClassification code 10025120Term: Lung squamous cell carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10025124Term: Lung squamous cell carcinoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10014749Term: Endometrial carcinoma stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10014751Term: Endometrial carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10025125Term: Lung squamous cell carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10014750Term: Endometrial carc; MedDRA version: 19.0Level: LLTClassification code 10014743Term: Endometrial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: PTClassification code 10071533Term: Lung squamous cell carcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.0Level: LLTClassification code 10014747Term: Endometrial carcinoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2016-001352-21-ES
• Lead Sponsor: Ability Pharmaceuticals, S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-07-15
• Last Update Posted: 9 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Patients =18 years of age
For endometrial cancer: Patients with histologically or radiological/cytologically confirmed diagnosis of advanced, metastatic or recurrent endometrial cancer
For squamous NSCLC: Patients with histologically or radiological/cytologically confirmed diagnosis (non irradiable IIIb stage or stage IV)
Have adequate tumor tissue available (either archival or new tumor biopsy) for biomarker analyses.
Life expectancy = 12 weeks in the opinion of the investigator
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 guidelines with at least one target lesion to be used to assess response.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Contraception: Female patients 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.
Adequate bone marrow function defined as:
- absolute neutrophil count = 1.5x109/L
- platelet count = 100x109/L
- hemoglobin = 9.0 g/dL
Total bilirubin = 1.5 x upper limit of normal
AST = 2.5 times upper limit of normal (ULN) (=5 times the ULN in patients with evidence of liver metastases)
Alkaline phosphatase = 2.5 times ULN (=5 times the ULN in patients with evidence of liver metastases)
Glomerular filtration rate = 50 mL/min
Serum creatinine =1.5 mg/dL
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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

Patients previously treated with an inhibitor of the PI3K/Akt/mTOR pathway.
Patients with symptomatic brain metastases.
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.
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 pre-existing uncontrolled hypertension.
Patients with known Hepatitis B or C or human immunodeficiency virus (HIV) infection with non-controlled disease according to the treating physician.
Patients with any other medical conditions (such as psychiatric illness, infectious diseases, abnormal 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

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess safety and tolerability of ABTL0812 plus paclitaxel + carboplatin in patients with advanced or metastatic endometrial cancer or squamous NSCLC at first line therapy;Secondary Objective: To evaluate the efficacy of ABTL0812 plus paclitaxel + carboplatin in patients with advanced or metastatic endometrial cancer or squamous NSCLC at first line therapy<br>To evaluate the pharmacokinetics of ABTL0812<br>To evaluate biomarkers to monitor activity ABTL0812<br>To evaluate biomarkers for response prediction to ABTL0812<br>To determine the recommended Phase II Dose (RP2D) of ABTL0812 plus paclitaxel + carboplatin;Primary end point(s): To assess safety and tolerability of ABTL0812 plus paclitaxel + carboplatin in patients with advanced or metastatic endometrial cancer or squamous NSCLC at first line therapy;Timepoint(s) of evaluation of this end point: Phase I: every 3 weeks<br>Phase II: every 2 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. To evaluate the efficacy of ABTL0812 plus paclitaxel + carboplatin in patients with advanced or metastatic endometrial cancer or squamous NSCLC at first line therapy<br>2. To evaluate the pharmacokinetics of ABTL0812<br>3. To evaluate biomarkers to monitor activity ABTL0812<br>4. To evaluate biomarkers for response prediction to ABTL0812<br>5. To determine the recommended Phase II Dose (RP2D) of ABTL0812 plus paclitaxel + carboplatin;Timepoint(s) of evaluation of this end point: 1. Every 2 months aprox. <br>2. At study innitiation and 1 month after<br>3. At study innitiation and 1 month after<br>4. At study innitiation <br>5. At the end of de-escalation phase (phase I)