A Study to Assess the Efficacy and Safety of ABTL0812

Brief Title

A Study to Assess the Efficacy and Safety of ABTL0812

Official Title

A Phase I/II, Open Label Study to Assess the Efficacy and Safety of ABTL0812 in Combination With Paclitaxel and Carboplatin in Patients With Advanced Endometrial Cancer or Squamous NSCLC

Brief Summary

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

Detailed Description

      This is a phase I/II multicenter divided in two phases.

      Phase I: Safety and dose escalation

      This study is not randomized, and all included patients will receive ABTL0812 in addition to
      paclitaxel + carboplatin (SOC). In this phase, patients can be selected from both
      indications, regardless of the number of each indication.

      This phase will be divided in 2 periods:

      Period 1:

      A dose de-escalation phase will be performed with a 3 + 3 design, in which up to four
      different ABTL0812 dose levels will be tested in combination with SOC. Then, 12 patients will
      be included in an expansion phase. All patients will receive one week of ABTL0812 alone
      followed by ABTL0812 + SOC (up to 8 SOC cycles) as combined treatment.

      Period 2:

      After the finalization of the SOC cycles, ABTL0812 will be taken as single therapy, at 1300
      mg tid, up to 12 months from initiation of period 1. This is the Recommended Phase 2 Dose
      (RP2D) as monotherapy for ABTL0812 determined in the previous phase I clinical trial.

      Phase II: Efficacy and safety

      This phase of the study will include up to 33 patients per indication (up to 66 patients
      overall). The final number will depend on the number of patients included in the phase I. The
      number of patients selected per indication will depend on the number already selected in
      phase I, as it is necessary to compensate both indications to have a final number of 40
      patients per indication approximately.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Emergent Adverse Events

Secondary Outcome

 Objective response rate (ORR)

Condition

Endometrial Cancer

Intervention

ABTL0812 in combination with paclitaxel and carboplatin

Study Arms / Comparison Groups

 Endometrial cancer

Description:  ABTL0812 (starting 1,300 mg tid orally) in combination with paclitaxel and carboplatin will be given to patients with advanced endometrial cancer, up to 12 months from initiation.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

103

Start Date

December 1, 2016

Completion Date

November 15, 2020

Primary Completion Date

June 1, 2020

Eligibility Criteria

        Inclusion Criteria:

          -  Patients ≥18 years of age

          -  Willing and able to provide informed consent

          -  For endometrial cancer: Patients with advanced, metastatic or recurrent endometrial
             cancer, from all histological types except carcinosarcoma and leiomyosarcoma.

          -  For squamous NSCLC: Patients with histologically or radiological/cytologically
             confirmed diagnosis (non-irradiance IIIb stage or stage IV), excluding mixed tumors,
             neuroendocrine or adenocarcinoma.

          -  Have adequate tumor tissue available (either archival not older than 6 months or new
             tumor biopsy) for biomarker analyses. The most recently collected tumor tissue sample
             should be provided, if available.

          -  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. Tumors
             within a previously irradiated field will be designated as "non-target" lesions unless
             progression is documented.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

          -  Contraception: All female patients 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 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. Male patients 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 defined as:

               -  absolute neutrophil count ≥ 1.5x109/L

               -  platelet count ≥ 100x109/L

               -  hemoglobin ≥ 10.0 g/dL

          -  Total bilirubin ≤ 1.5 x upper limit of normal

          -  Aspartate transaminase (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 ULN

          -  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 previously treated with an inhibitor of the Phosphoinositide 3-kinase/Protein
             kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) pathway.

          -  Patients previously treated with adjuvant or co-adjuvant chemotherapy administered 6
             months or less in advance of patient inclusion

          -  Patients with symptomatic brain metastases. Patients with asymptomatic and treated
             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 provided they don't have
             peripheric neuropathy grade 2 or superior.

          -  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 pre-existing uncontrolled hypertension. Patients whose hypertension is
             controlled by antihypertensive therapies are eligible.

          -  Patients with active 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Ana Oaknin, , 

Location Countries

Spain

Location Countries

Spain

NCT ID

NCT03366480

Organization ID

ABT-C5-2016

Secondary IDs

2016-001352-21

Responsible Party

Sponsor

Study Sponsor

Ability Pharmaceuticals SL

Collaborators

 Hospital Vall d'Hebron

Study Sponsor

Ana Oaknin, Principal Investigator, VHIO

Verification Date

June 2021