Study of the safety, activity, and effect on the body of ASTX660 in people with advanced cancers.

Phase 1

• Conditions: Advanced Solid Tumors and Lymphomas that are metastatic or unresectable: cohort 1:Recurrent/metastatic head and neck squamous cell carcinoma; cohort 2:Relapsed or refractory diffuse large B-cell lymphoma; cohort 3:Progressive or relapsed peripheral T-cell lymphoma; cohort 4:Relapsed or refractory cutaneous T-cell lymphoma; cohort 5: Other tumor types that may have sensitivity to ASTX660: cohort 6: Cervical carcinoma not responsive or relapsed after standard therapy; MedDRA version: 20.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10011677Term: Cutaneous T-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10034623Term: Peripheral T-cell lymphoma unspecifiedSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2016-005039-34-FR
• Lead Sponsor: Astex Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-27
• Last Update Posted: 28 May 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Subjects must fulfill all of the following inclusion criteria.
1. Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
2. Men and women 18 years of age or older.
3. Subjects with histologically or cytologically confirmed advanced solid tumors or lymphoma that is metastatic or unresectable, and for whom standard life-prolonging measures are not available.
4. Subjects must have measurable disease according to RECIST v1.1, or evaluable disease that can be reliably and consistently followed.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
6. Acceptable organ function, as evidenced by the following laboratory data:
a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.0 × upper limit of normal (ULN).
b. Total serum bilirubin =1.5 × ULN.
c. Absolute neutrophil count (ANC):
o (except subjects with known lymphoma): =1500 cells/mm3.
o subjects with known lymphoma: =1000 cells/mm3 (=750 cells/mm3 for subjects with lymphoma in bone marrow).
d. Platelet count:
o (except subjects with known lymphoma): =100,000 cells/mm3.
o subjects with known lymphoma: =50,000 cells/mm3 (=25,000 cells/mm3 for subjects with lymphoma in bone marrow).
e. Serum creatinine levels =1.5 × ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measured creatinine clearance =50 mL/min.
7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and all men with female partners of child-bearing potential must be practicing 2 medically acceptable methods of birth control and must not become pregnant or father a child while receiving treatment with study drug and for at least 3 months after completing treatment
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 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1. Hypersensitivity to ASTX660, excipients of the drug product, or other components of the study treatment regimen.
2. Poor medical risk because of systemic diseases (eg, active uncontrolled infections) in addition to the qualifying disease under study.
3. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator’s opinion, could compromise subject safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of ASTX660.
4. History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
a) Abnormal left ventricular ejection fraction (LVEF; <50%) on echocardiogram (ECHO) or multiplegated acquisition scan (MUGA). [Applies to Phase 1 only; ECHO/MUGA scans are not performed in Phase 2.]
b) Congestive cardiac failure of = Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as subjects with marked limitation of activity and who are comfortable only at rest.
c) Unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
d) History or presence of complete left bundle branch block, heart block, cardiac pacemaker or significant arrhythmia.
e) Concurrent treatment with any medication that prolongs QT interval and may induce torsades de pointes, and which cannot be discontinued at least 2 weeks before treatment with ASTX660. [Applies to Phase 1 only.]
f) Personal history of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy.
g) Screening 12-lead ECG with measurable QTc interval (according to either Fridericia's or Bazett’s correction) of =470 msec).
5. Known history of human immunodeficiency virus (HIV) infection, or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
6. Grade 2 or greater neuropathy. [Applies to Phase 1 only.]
7. Known brain metastases, unless stable or previously treated.
8. Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments.
9. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX660), as follows:
• Cytotoxic chemotherapy or radiotherapy within 3 weeks prior and any encountered treatment-related toxicities (excepting alopecia) not resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
• Monoclonal antibodies within 4 weeks prior and any encountered treatment-related toxicities not resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
• Investigational drugs (small molecules or biologics) within the longer of 2 weeks or 5 half-lives prior to study treatment and any encountered treatment-related toxicities not resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].

Study & Design

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