Dual mTOR Inhibitor MLN0128 in Advanced Castration-Resistant Prostate Cancer (CRPC) Patients

NCT02091531 | Completed Phase 2 Results

• 1 other identifier: 13-143
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study which will test the study drug MLN0128 in patients with castration resistant prostate cancer who have received chemotherapy in the past. Phase II clinical trials test how well an investigational drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it. MLN0128 is not approved by the FDA. The purpose of this study is to see what effects (good and bad) the study drug MLN0128 has on the patient and the cancer. MLN0128 is a drug that belongs to a class of drugs called "mTOR kinase inhibitors". A protein, called "mTOR" inside the cells in the body, plays a role in controlling how cells grow. In some cancer cells, mTOR may be over-active. This over-activity may cause some cancer cells to grow out of control. Research has shown that mTOR inhibitors can block this overactivity and may help stop or slow down the growth of some types of cancer cells.

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

mTOR Inhibitor MLN0128; PSA; 13-143

Outcome Measures

Primary Outcomes (1)

• Median Time on Treatment

  from the start of treatment, as defined by the Prostate Cancer Working Group 2 (PCWG2) guidelines.

  Up to 8 months

Secondary Outcomes (2)

• Median PSA Rise at End of Treatment as Compared to Baseline

  Duration of Treatment, up to 30 weeks

• Best Response

  Duration of Treatment, up to 30 weeks

Study Arms (1)

MLN0128

EXPERIMENTAL

Patients will be treated with the established phase II dose of MLN0128 (4mg po daily continuously; 1 cycle=4 weeks) to assess mechanisms of sensitivity and resistance in men with CRPC who have received either enzalutamide and/or abiraterone.

Drug: MLN0128

Interventions

MLN0128 DRUG

MLN0128

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed prostate cancer with progressive metastatic disease based on any of the following: i) a rise in PSA, ii) transaxial imaging, or iii) radionuclide bone scan.
• PSA - a minimum of 3 consecutive rising levels, with an interval of ≥
• week between each determination. The last determination must have a minimal value of ≥ 2 ng/mL and be determined within two weeks prior to enrollment.
• Measurable Disease - patients showing new or progressive soft tissue masses on CT or MRI scans as defined by the PCWG2 criteria21
• Radionuclide bone scan - at least two new metastatic lesions.
• Detectable metastases by bone scan, CT-scan or MRI.
• Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone (GnRH) analogue or inhibitor, or orchiectomy (i.e., surgical or medical castration).
• For patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
• Castrate levels of serum testosterone \< 50 ng/dL determined within 4 weeks prior to starting treatment.
• Patients who are receiving an anti-androgen as part of their first-line hormonal therapy must have shown progression of disease off the anti-androgen prior to enrollment.
• At least 4 weeks must have elapsed from the use of androgen receptor antagonists (i.e., flutamide, nilutamide, bicalutamide, enzalutamide ); 5-α reductase inhibitors (i.e., finasteride, aminoglutethimide); abiraterone acetate; estrogens; nitrosoureas, mitomycin C, isotype therapy, ketoconazole, chemotherapy and other anti-cancer pharmacologic therapy prior to beginning protocol therapy.
• At least 8 weeks must have elapsed from the use of Strontium-89, Radium-223, Samarium-153, or immunotherapy (e.g., Provenge) prior to beginning protocol therapy.
• At least 4 weeks must have elapsed from the use of any investigational agent prior to beginning protocol therapy.
• a. Note: Prior treatment with PI3K/mTOR pathway inhibitors prohibited.
• At least 4 weeks must have elapsed from major surgery.

You may not qualify if:

• Patients that meet any of the criteria listed below will not be eligible for study entry:
• History of, or current known metastases in the brain or untreated spinal cord compression;
• History of another malignancy within the previous 2 years except for the following:
• Adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer,
• Adequately treated Stage I or II cancer currently in complete remission, or any other cancer that has been in complete remission for at least 2 years;
• Prior treatment with PI3K/mTOR pathway inhibitors;
• Diabetes mellitus on active treatment, or subjects with either of the following:
• Fasting blood glucose (FBG) ≥ 126 mg/dL (7.0 mmol/L), or
• HbA1c ≥ 6.5%;
• Use of herbal products that may decrease PSA levels (i.e., saw palmetto) or systemic corticosteroid greater than the equivalent of 10 mg of prednisone per day during the 4 weeks prior to screening or plans to initiate treatment with the above during the entire duration of the study;
• Any history of unstable angina, myocardial infarction, New York Heart Association (NYHA) Class III or IV heart failure, and/or pulmonary hypertension;
• Significant active cardiovascular disease including:
• a. Uncontrolled high blood pressure (ie, systolic blood pressure \> 180 mmHg, diastolic blood pressure \> 95 mmHg) b. Grade 3 or higher valvular disease c. Grade 3 or higher atrial fibrillation d. Grade 3 or higher bradycardia e. Endocarditis f. Pulmonary embolism g. Recent cerebrovascular accident within 6 months prior to enrollment
• A requirement for positive inotropic support (excluding digoxin) or serious uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 1 year prior to screening
• A pacemaker or implantable cardiac defibrillator

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

sapanisertib

Results Point of Contact

• Title: Dr. Dana Rathkopf, MD
• Organization: Memorial Sloan Kettering Cancer Center

rathkopd@mskcc.org

646-422-4379

Study Officials

• Dana Rathkopf, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: March 14, 2014
• First Posted: March 19, 2014
• Study Start: March 1, 2014
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: November 21, 2019
• Results First Posted: October 29, 2019

Record last verified: 2018-10

Locations

US (1)