Paclitaxel and TAK-228 in Urothelial Carcinoma

NCT03745911 | Unknown Phase 2

• 2 other identifiers: X310052017-004486-27
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 5

Brief Summary

Phase II Multicentre, single arm, open label study of Paclitaxel and TAK-228 in metastatic urothelial carcinoma (UC) and the impact of PI3K-mTOR pathway genomic alterations

Conditions

Metastatic Urothelial Cancer

Keywords

Urothelial carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate (ORR), defined as the sum of the complete and partial responses (CR+PR), with the goal of increasing the rate from 10% to 26%. Response rates will be measured using RECIST 1.1 criteria

  34 months

Secondary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  34 months

• Progression-Free Survival (PFS)

  34 months

• Overall Survival (OS)

  34 months

Other Outcomes (6)

• Characterization of PI3K/ AKT/ mTOR pathway mutations

  34 months

• Characterization of PI3K/ AKT/ mTOR pathway mutations

  34 months

• Characterization of PI3K/ AKT/ mTOR pathway mutations

  34 months

Study Arms (1)

Paclitaxel plus TAK-228

EXPERIMENTAL

* Paclitaxel will be given on days 1, 8, and 15 of each 28 day cycle intravenously (every Monday or first day of business week if holiday), the day before the first TAK-228 dose. It should be given over approximately one hour. * TAK-228 will be given orally on Days 2-4, 9-11, 16-18 and 23-25 of each 28-day cycle.

Combination Product: Paclitaxel and TAK-228

Interventions

Paclitaxel and TAK-228 COMBINATION_PRODUCT

Treatment with TAK-228 oral (D2, 3 and 4 of each week) and paclitaxel (D1 of each week) on Days 1, 8 and 15 for each 28-days cycle until disease progression or unacceptable toxicity. If paclitaxel is stopped, TAK-228 may be continued

Paclitaxel plus TAK-228

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years or older.
• Patients must have a diagnosis of metastatic or advanced histologically confirmed UC (urothelial cancer). Mixed histologies are allowed.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 1 effective method of contraception and 1 additional effective (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer as mandated by local labeling \[e.g., USPI, SmPC, etc,\]) after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
• Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
• Agree not to donate sperm during the course of this study or within 120 days after receiving their last dose of study drug
• Screening clinical laboratory values as specified below:
• Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL without transfusion within 1 week preceding study drug administration.
• Hepatic: total bilirubin ≤ 1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present);

You may not qualify if:

• Prior treatment with paclitaxel for UC (in any setting - neoadjuvant, adjuvant or for metastatic disease). Patients treated with prior docetaxel are eligible.
• Previous treatment with PI3K, AKT, dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK-228. In addition, patients with enteric stomata are also excluded.
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
• History of any of the following within the last 6 months prior to study entry:
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• Ischemic cerebrovascular event, including TIA and artery revascularization procedures
• Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
• Placement of a pacemaker for control of rhythm
• New York Heart Association (NYHA) Class III or IV heart failure (See Appendix C)
• Pulmonary embolism.
• Significant active cardiovascular or pulmonary disease at the time of study entry, including:
• Uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1 Day 1 is allowed.
• Pulmonary hypertension.
• Uncontrolled asthma or O2 saturation \< 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry on room air.

Sponsors & Collaborators

• Associació per a la Recerca Oncologica, Spain: lead
• Takeda: collaborator
• Pivotal S.L.: collaborator

Study Sites (5)

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

RECRUITING

Parc Taulí Hospital Universitario

Sabadell, Barcelona, 08208, Spain

RECRUITING

Clínica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

RECRUITING

Hospital del Mar

Barcelona, 08003, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

RECRUITING

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MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Paclitaxel; sapanisertib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Joaquín Bellmunt, MD/PhD

  Hospital del Mar

  PRINCIPAL INVESTIGATOR

• Alejo Rodríguez-Vida, MD/PhD

  Hospital del Mar

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joaquím Bellmunt, MD/PhD

CONTACT

+34 932 483 860; jbellmunt@imim.cat

Inmaculada Musté

CONTACT

+34 932 274 760; oncologia.apro@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2018
• First Posted: November 19, 2018
• Study Start: May 4, 2018
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: November 19, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)