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 Information
Recruitment Status
Drug
Estimated Enrollment
80
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, , [email protected]
Location Countries
Spain
Location Countries
Spain
Administrative Informations
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
February 2019