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TAK228 With Carbo and Taxol in Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03430882
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : September 3, 2018
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerable dose of the combination of TAK-228, carboplatin, and paclitaxel that can be given to patients with advanced cancer. The safety of the drug combination will also be studied.

This is an investigational study. TAK-228 is not FDA approved or commercially available. TAK-228 is currently being used for research purposes only. Carboplatin and paclitaxel are both FDA approved and commercially available for the treatment of various cancers. The combination of carboplatin and paclitaxel is frequently used in clinical practice. The combination of these drugs with TAK-228 to treat advanced cancer is considered investigational.

The study doctor can explain how the study drugs are designed to work.

Up to 50 participants will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Malignant Neoplasm of Breast Malignant Neoplasms of Bone and Articular Cartilage Malignant Neoplasms of Digestive Organs Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System Malignant Neoplasms of Female Genital Organs Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites Malignant Neoplasms of Independent (Primary) Multiple Sites Malignant Neoplasms of Lip Oral Cavity and Pharynx Malignant Neoplasms of Male Genital Organs Malignant Neoplasms of Mesothelial and Soft Tissue Malignant Neoplasms of Respiratory and Intrathoracic Organs Malignant Neoplasms of Thyroid and Other Endocrine Glands Malignant Neoplasms of Urinary Tract Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic Drug: TAK-228 Drug: Paclitaxel Drug: Carboplatin Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of TAK-228 (MLN0128) in Combination With Carboplatin Plus Paclitaxel in Patients With Advanced Malignancies
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAK-228 + Paclitaxel + Carboplatin

Participants take TAK-228 by mouth at about the same time each day on Days 2-4, 9-11, and 16-18 of Cycles 1-6. Participants then take TAK-228 on Day 1 of Cycles 7 and beyond.

Participants receive Carboplatin by vein over about 60 minutes on Day 1 of Cycles 1-6.

Participants receive Paclitaxel by vein over about 3 hours on Days 1, 8, and 15 of Cycles 1-6.

Each cycle is 21 days.

Drug: TAK-228

Dose Escalation Starting Dose of TAK-228: 2 mg by mouth at about the same time each day on Days 2-4, 9-11, and 16-18 of Cycles 1-6. Participant then takes TAK-228 on Day 1 of Cycles 7 and beyond.

Dose Expansion Starting Dose of TAK-228: Maximum tolerated dose from Dose Escalation Phase.

Other Names:
  • MLN0128
  • TAK228

Drug: Paclitaxel

Dose Escalation Starting Dose of Paclitaxel: 40 mg/m2 by vein weekly for 6, 21 day cycles.

Dose Expansion Starting Dose of Paclitaxel: Maximum tolerated dose from Dose Escalation Phase.

Other Name: Taxol

Drug: Carboplatin

Dose Escalation Starting Dose of Carboplatin: AUC 5 by vein on Day of cycles 1-6.

Dose Expansion Starting Dose of Carboplatin: Maximum tolerated dose from Dose Escalation Phase.

Other Name: Paraplatin




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of TAK-228 in Combination With Carboplatin Plus Paclitaxel in Patients With Advanced Malignancies [ Time Frame: Start of study drug up to 21 days ]
    MTD is the highest dose level in which 6 patients have been treated with at most 1 experiencing dose limiting toxicity (DLT). Toxicities graded using NCI CTCAE v4.0 toxicity criteria.


Secondary Outcome Measures :
  1. Clinical Response of TAK-228 in Combination With Carboplatin Plus Paclitaxel in Patients With Advanced Malignancies [ Time Frame: Start of drug combination up to 6 months ]
    Categorization of response based on RECIST v1.1.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients 18 years or older.
  2. Patients must have a diagnosis of a solid tumor malignancy and is refractory to standard therapies who have relapsed after standard therapy, or whose cancers have no standard therapy.
  3. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status <=1.
  4. 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.)
  5. Continued from Inclusion Criteria # 4: 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.
  6. Screening clinical laboratory values as specified below: a) Bone marrow reserve consistent with: absolute neutrophil count (ANC) >/= 1.5 x 10^9/L; platelet count >/= 100 x 10^9/L; hemoglobin >/= 9 g/dL without transfusion within 1 week preceding study drug administration b) 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); c) Renal: creatinine clearance >/=50 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour); d) Metabolic: Glycosylated hemoglobin (HbA1c)<7%, fasting serum glucose (</= 130 mg/dL) and fasting triglycerides </= 300 mg/dL
  7. Ability to swallow oral medications.
  8. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  9. Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met: a) Brain metastases which have been treated b) No evidence of disease progression for >/= 3 months before the first dose of study drug. c) No hemorrhage after treatment d) Off-treatment with dexamethasone for 4 weeks before administration of the first dose of TAK-228 e) No ongoing requirement for dexamethasone or anti-epileptic drugs.
  10. Patients must have evaluable or measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
  11. Patients must be 4 weeks beyond previous treatment of any chemotherapy or radiotherapy, and must have recovered to </= grade 1 or previous baseline for each toxicity. Exception: Patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field. Patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 weeks, whichever is shorter, from the last day of treatment of non-chemotherapeutic biological agents.

Exclusion Criteria:

  1. Carboplatin or Paclitaxel exposure within past 6 months
  2. Central nervous system (CNS) metastasis.
  3. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
  4. Known history of human immunodeficiency virus infection.
  5. Known history of hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
  6. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  7. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  8. Breast feeding or pregnant.
  9. Treatment with any investigational products within 4 weeks before the first dose of study drug.
  10. Previous treatment with dual PI3K/mTOR inhibitors, TORC1/2 inhibitors or TORC1 inhibitors.
  11. 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.
  12. History of any of the following within the last 6 months before administration of the first dose of the drug: a) Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures b) Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures c) Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) d) Placement of a pacemaker for control of rhythm e) New York Heart Association (NYHA) Class III or IV heart failure f) Pulmonary embolism.
  13. Significant active cardiovascular or pulmonary disease including: a) Uncontrolled hypertension (i.e., systolic blood pressure >150 mm Hg, diastolic blood pressure > 90 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle1 Day 1 is allowed. b) Pulmonary hypertension c) Uncontrolled asthma or O2 saturation < 90% by arterial blood gas analysis or pulse oximetry on room air d) Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement e) Medically significant (symptomatic) bradycardia f) History of arrhythmia requiring an implantable cardiac defibrillator g) Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes).
  14. Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c) > 7%; patients with a history of transient glucose intolerance due to corticosteroid administration may be enrolled in this study if all other inclusion/exclusion criteria are met.
  15. Patients receiving systemic corticosteroids (either IV or oral steroids, excluding inhalers or low-dose hormone replacement therapy) within 1 week before administration of the first dose of study drug.
  16. Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days before receiving the first dose of study drug.
  17. Patients with hypersensitivity or other allergic reaction to platinum chemotherapy.
  18. Patients with hypersensitivity or other allergic reaction to taxanes.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03430882


Contacts
Contact: Vivek Subbiah, MD 713-563-1930 vsubbiah@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact       vsubbiah@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Takeda
Investigators
Principal Investigator: Vivek Subbiah, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03430882     History of Changes
Other Study ID Numbers: 2016-0845
NCI-2018-00989 ( Registry Identifier: NCI CTRP )
First Posted: February 13, 2018    Key Record Dates
Last Update Posted: September 3, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Solid tumor malignancy
TAK-228
MLN0128
TAK228
Paclitaxel
Taxol
Carboplatin
Paraplatin

Additional relevant MeSH terms:
Neoplasms
Breast Neoplasms
Genital Neoplasms, Female
Bone Neoplasms
Lip Neoplasms
Genital Neoplasms, Male
Urologic Neoplasms
Thyroid Neoplasms
Cartilage Diseases
Soft Tissue Neoplasms
Neoplasms, Fibrous Tissue
Eye Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Urogenital Neoplasms
Bone Diseases
Musculoskeletal Diseases
Mouth Neoplasms
Head and Neck Neoplasms
Lip Diseases
Mouth Diseases
Stomatognathic Diseases
Genital Diseases, Male
Endocrine Gland Neoplasms
Endocrine System Diseases
Thyroid Diseases
Connective Tissue Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue