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, refractory 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: 21.0Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 22.0Level: PTClassification code 10011677Term: Cutaneous T-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10067821Term: Head and neck cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10008229Term: Cervical cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: 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-ES
• Lead Sponsor: Astex Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-02-28
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 230

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.
a) For Phase 2 Cohort 3, subjects must have histologically confirmed PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study: adult T-cell lymphoma/leukemia, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, nodal peripheral T-cell with T-follicular helper (THF) phenotype, and anaplastic large-cell lymphoma.
4. For Phase 2 Cohorts 3 and 4, patients must have evidence of documented progressive disease and must have received at least two prior systemic therapies [Phase 2 Cohort 3 and 4].
a) Subjects with CD30-positive lymphoma must have received, be ineligible for, or intolerant to brentuximab vedotin.
b) Subjects with mycosis fungoides or Sezary syndrome must have received, be ineligible, or intolerant to mogamulizumab.
5. In the Phase 2 portion of the protocol only, subjects must have measurable disease according to response criteria appropriate to their type of cancer (as explained in Section 9.1).
a) For Phase 2 Cohort 3 (PTCL), measurable disease by contrast-enhanced diagnostic CT (at least 1 nodal lesion =1.5 cm or extranodal lesions >1.0 cm) is required.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7. 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 Phase 1 and 2 (except subjects with known lymphoma): =1500 cells/mm3.
o Phase 2 subjects with known lymphoma: =1000 cells/mm3 (=750 cells/mm3 for subjects with lymphoma in bone marrow) (Administration of myeloid growth factors within 14 days prior to study entry are not allowed).
d. Platelet count:
o Phase 1 and 2 (except subjects with known lymphoma): =100,000 cells/mm3.
o Phase 2 subjects with known lymphoma: =50,000 cells/mm3 (=25,000 cells/mm3 for subjects with lymphoma in bone marrow) (transfusion within 21 days prior to study entry are not allowed).
e. Serum creatinine levels =1.5 × ULN, or calculated (by Cockcroft-Gault formula or other accepted formula) or measured creatinine clearance =50 mL/min.
f. Amylase and lipase =ULN. [Applies to Phase 2].
8. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]; see protocol for details) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control (as describe

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 both Phase 1 and 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, third-degree heart block, cardiac pacemaker or clinically 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).
h) Any other condition that, in the opinion of the investigator, could put
the subject at increased cardiac risk.
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 ]. Grade 3 or greater neuropathy [Applies to Phase 2].
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:
a) Cytotoxic chemotherapy or radiotherapy within 3 weeks prior (6 weeks if nitrosoureas). Palliative radiotherapy to a single lesion within 2 weeks prior. Any encountered treatment-related toxicities (excepting alopecia) must be stabilized or resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
b) Skin directed treatments, including topicals and radiation within 2 weeks prior.
c) Monoclonal antibodies within 4 weeks prior. Any encountered treatment-related toxicities must be stabilized or resolved to Grade 1 or less [Phase 1] or Grade 2 or less [Phase 2].
d) At least 6 weeks must have elapsed since CAR-T infusion and subjects must have experienced disease progression, and not have residual circulating CAR-T cells in peripheral blood (based on local assessment). Any encountered treatment-related toxicities must have resolved to Grade =1.
e) Investigational drugs (small molecules

Study & Design

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