Hepatocellular CarcinomaPhase 1/2NCT02575339
MLN0128 Compared to Sorafenib in Advanced or Metastatic Hepatocellular Carcinoma
A Phase 1/2 study testing MLN0128, MLN0128 (RP2D) and Sorafenib in people with Hepatocellular Carcinoma and Liver Cancer, run by Kathy Miller at 6 sites in United States.
Trial summary
This is an open label, multi-center, randomized phase I/II study of MLN0128 versus standard sorafenib. Eligible subjects in the phase I trial will receive MLN0128 in escalating doses. Eligible subjects in the phase II trial will be 1:1 randomized to either the MLN0128 arm or the sorafenib arm. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Liver Cancer, HCC
- What is being tested?
- MLN0128, MLN0128 (RP2D) and Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 6 sitesUnited States
- Study dates
- 18 Jul 2016to 24 Nov 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects 18 years or older at the time of informed consent.
- Voluntary written consent must be signed before performance of any study related procedure not part of standard medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
- Females of childbearing potential must agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
- Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to prior to registration for protocol therapy. NOTE: Female subjects are considered of childbearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Male subjects, even if surgically sterilized (i.e., status post-vasectomy), must agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
- Subjects must have a diagnosis of measurable advanced or metastatic hepatocellular carcinoma (HCC). Advanced HCC is defined as disease not amenable to surgery, ablation, transplant, or embolic therapy.
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- Phase II subjects must be willing to provide a tissue biopsy prior to registration if archived HCC tumor tissue is not available for correlative studies.
- For the phase I cohort, subjects with one prior systemic treatment are eligible.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
- Adequate organ function, as specified below, within 28 days before study registration:
- Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; platelet count ≥ 50 x 10^9/L; hemoglobin ≥ 9 g/dL;
- Hepatic: total bilirubin ≤ 2 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤ 5 x ULN
- Renal: creatinine clearance ≥50 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour);
- Metabolic: Glycosylated hemoglobin (HbA1c) ≤7.0%, fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL.
- Ability to swallow oral medications.
- Measurable disease according to RECIST v1.1 and obtained by imaging within 28 days prior to registration for protocol therapy.
- Subjects who have a history of brain metastasis are eligible for the study provided all the following criteria are met:
- Must have completed their treatment for brain metastasis
- Must be asymptomatic
- Must not have evidence of disease progression for ≥3 months or hemorrhage after treatment;
- Must be off-treatment from dexamethasone for 4 weeks prior to study registration and
- Must not have an ongoing requirement for dexamethasone or anti-epileptic drugs.
- Prior locoregional liver directed therapy is allowed as long as treatment was at least 6 weeks prior to study registration, and clear progression is demonstrated by RECIST v1.1 criteria. Subject must have recovered from the acute toxic effects (≤ grade 1 CTCAE v4) of previous anti-cancer treatment prior to study enrollment; the only exception is that grade 2 neuropathy is permitted.
- Prior radiation therapy is allowed to < 25% of the bone marrow, but is not permitted within 28 days prior to study registration.
- Estimated life expectancy > 3 months as determined by the treating physician.
Who cannot join
- Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:
- Female subjects who are both lactating and breastfeeding
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Treatment with any investigational products within 28 days prior to study registration.
- No prior systemic treatment is allowed, except for subjects in the phase I cohort who are permitted one prior systemic treatment.
- Failed to recover from the reversible effects of prior anticancer therapies with the exception of alopecia and grade 2 neuropathy.
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- Have initiated treatment with bisphosphonates less than 30 days prior to study registration. Concurrent bisphosphonate use is only allowed if the bisphosphonate was initiated at least 30 days prior to study registration.
- Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128.
- No condition that could affect the absorption of study drug, including any of the following:
- Malabsorption syndrome
- Disease significantly affecting gastrointestinal function
- Bowel obstruction or sub-obstruction
- History of any of the following within the last 6 months prior to study registration:
- Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
- Ischemic cerebrovascular event, including transient ischemic attack (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
- Pulmonary embolism
- Significant active cardiovascular or pulmonary disease at the time of study registration, including:
- Uncontrolled high blood pressure (i.e., systolic blood pressure >160 mm Hg, diastolic blood pressure > 95 mm Hg)
- Pulmonary hypertension
- Uncontrolled asthma or O2 saturation < 90% by ABG (Arterial Blood Gas) analysis or pulse oximetry on room air
- Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement
- Medically significant (symptomatic) bradycardia
- History of arrhythmia requiring an implantable cardiac defibrillator
- 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)
- Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids (either IV or oral steroids, excluding inhalers) within 1 week prior to study registration (subjects already receiving erythropoietin on a chronic basis for ≥ 28 days are eligible).
- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise participation of the subject in the study.
- Cirrhosis with Child-Pugh score > 7
- Variceal bleeding within 1 month prior to study registration.
- Refractory encephalopathy or ascites
- Known HIV positivity
- Hepatitis B surface antigen (HBsAg) positivity without active treatment. A subject found to be HBsAg positive should be on antiviral therapy for at least two weeks prior to study registration.
- Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4, CYP2C19 or CYP2C19 within 7 days prior to study registration.
- Subjects requiring daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI within 7 days prior to study registration.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Noth Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
University of Illinois Cancer Center
Chicago, Illinois, 60612
Penn State Cancer Institute
Hershey, Pennsylvania, 17033
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
University of Wisconsin
Madison, Wisconsin, 53705
About this study
Official title: An Open Label Randomized Phase I/II Trial of MLN0128 Compared to Sorafenib in Patients With Advanced or Metastatic Hepatocellular Carcinoma: Big Ten Cancer Research Consortium BTCRC-GI13-002
This is an open label, multi-center, randomized phase I/II study of MLN0128 versus standard sorafenib. Eligible subjects in the phase I trial will receive MLN0128 in escalating doses. Eligible subjects in the phase II trial will be 1:1 randomized to either the MLN0128 arm or the sorafenib arm.
Read the detailed description
OUTLINE: This is a multi-center trial.
The phase 1 dose escalation trial will evaluate MLN0128 in a standard 3+3 successive cohort design to identify the highest planned dose level. Phase II trial subjects will be 1:1 randomized to receive either MLN0128 (investigational arm) or sorafenib (control arm).
PHASE I DOSE ESCALATION INVESTIGATIONAL TREATMENT:
Cohort 1 (dose level +1) will consist of 3-6 evaluable patients who will receive MLN0128 15mg on day 1 of the 28-day cycle.
Cohort 2 (dose level +2) will consist of 3-6 evaluable patients who will receive MLN0128 20mg on day 1 of the 28-day cycle.
Cohort 3 (dose level +3) will consist of 3-6 evaluable patients who will receive MLN0128 30mg on day 1 of the 28-day cycle.
Subjects will be evaluated for dose limiting toxicity (DLT) in the first 28 days of treatment (1 cycle). However, decisions to move to next dose escalation cohort will not be made until all subjects complete 2 cycles of therapy at a given dose. There will be no further dose escalation beyond dose level +3.
PHASE II INVESTIGATIONAL TREATMENT:
Randomization will take place following completion of the screening evaluations and eligibility assessments. Stratification factors will be employed during randomization to minimize between-arm assignment imbalance.
- 1 Child-Pugh score 5-6
- 2 Child-Pugh score 7
Within the strata, subjects will be randomly assigned with equal probability to either the investigational arm (Arm A: MLN0128) or the control arm (Arm B: sorafenib).
Arm A: MLN0128 will be administered orally at the recommended phase II dose (RP2D) once weekly.
Arm B: Sorafenib will be administered at 400mg PO BID daily, with dose adjustment per standard of care.
A new treatment cycle (1 cycle = 28 days) will only be initiated when all of the following conditions are met:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
- Platelets ≥ 50 x 10*9/L
- Non-hematologic treatment related toxicities have improved to grade 1 or resolved per Common Terminology Criteria for Adverse Events v4.0 (CTCAE)
Treatment may continue until progression, unacceptable toxicity, or withdrawal from study.
Estimated Life Expectancy: ≥ 3 months
Subjects must have adequate organ function, as specified below, within 7 days before study registration:
Bone marrow reserve consistent with:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
- Platelet count ≥ 50 x 10*9/L
- Hemoglobin ≥ 9 g/dL
Hepatic:
- Total bilirubin ≤ 2 x upper limit of normal (ULN)
- Transaminases (aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN
Renal:
- Creatinine clearance ≥50 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour)
Metabolic:
- Fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL.
- Glycosylated hemoglobin (HbA1c) <7.0%
- Conditions
- Hepatocellular Carcinoma, Liver Cancer, HCC
- Being tested
- MLN0128, MLN0128 (RP2D), Sorafenib
- Keywords
- MLN0128, Sapanisertib, TORC1/2 inhibitor, INK128, Nexavar, Sorafenib
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN0128Drug
Also called Sapanisertib
Phase I Dose Escalation Study Cohort 1 MLN0128 15mg QW; Cohort 2 MLN0128 20mg QW; Cohort 3 MLN0128 30mg QW
MLN0128 (RP2D)Drug
Also called Sapanisertib
Phase II Arm A:
MLN0128 administered orally at the recommended phase II dose (RP2D) once weekly.
SorafenibDrug
Also called Nexavar
Phase II Arm B:
Sorafenib administered at 400mg PO BID daily
| Study group | Role | What they receive |
|---|---|---|
| Phase I MLN0128 Dose Escalation Study | Experimental | Subjects will receive MLN0128 orally on days 1, 8, 15 and 22 in successive cohorts.
Cohort 1 MLN0128 15mg each week (QW); Cohort 2 MLN0128 20mg QW; Cohort 3 MLN0128 30mg QW Receives: Drug: MLN0128 |
| Phase II Arm A: MLN0128 | Experimental | Subjects randomized to experimental arm will receive MLN0128 orally at the recommended phase II dose (RP2D) once weekly. Receives: Drug: MLN0128 (RP2D) |
| Phase II Arm B: Sorafenib | Active comparator | Subjects randomized to control arm will receive sorafenib 400mg by mouth (PO) twice a day (BID) daily. Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Maximum Tolerated Dose (MTD) of MLN0128
The primary objective for phase I of this study is to determine the maximum tolerated dose (MTD) of MLN0128.
Maximum Tolerated Dose is defined as the dose level at which fewer than 33% of subjects experience a dose limiting toxicity (DLT).
Measured: From start of treatment Day 1 (D1) until completion of two cycles of treatment (maximum 56 days)
Phase II: Time to Progression (TTP)
The primary endpoint of Phase II of the study is to evaluate the time to progression, which is defined as the time from randomization until tumor progression as defined by RECIST v1.1.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 7 months (estimated).
Secondary outcomes (10)
Phase I: Characterize Adverse Effects (AE)
Toxicity assessed using Common Terminology Criteria for Adverse Events v4.0 (CTCAE) criteria
Measured: From date of first dose until 30 days after the last treatment, assessed for estimated 7 cycles (est. 196 days)
Phase I: Overall Survival (OS) Rate
Overall Survival of subjects receiving MLN0128 is defined by the time from randomization to date of death from any cause.Here median overall survival in months has been reported for subjects per dose level with 95% confidence interval.
Measured: From date of registration until death from any cause, up to a maximum of 27 months
Phase II: Overall Survival (OS) Rate
Overall Survival of subjects randomized to both MLN0128 and sorafenib arms is defined by the time from randomization to date of death from any cause.
Measured: From date of registration until death from any cause, up to a maximum of 24 months
Phase I: Time to Progression (TTP)
Time to progression (TTP) of subjects receiving MLN0128 assessed using RECIST v1.1 criteria is defined as the time from randomization until tumor progression as defined by RECIST v1.1. Here median Time to Progression in months has been reported for subjects per dose level with 95% confidence interval.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 6 months (estimated).
Phase I: Progression-free Survival (PFS)
Progression free survival (PFS) of subjects receiving MLN0128 assessed using RECIST v1.1 criteria is defined by time from randomization to tumor progression or death from any cause. Here median Progression-free survival in months has been reported for subjects per dose level with 95% confidence interval.
Measured: From date of randomization to tumor progression or death from any cause, up to a maximum of 6 months
Phase II: Progression Free Survival (PFS)
Progression Free Survival of subjects randomized to both MLN0128 and sorafenib arms assessed using RECIST v1.1 criteria, is defined as time from randomization to tumor progression or death from any cause.
Measured: From date of randomization to tumor progression or death from any cause, up to a maximum of 24 months
Phase I: Objective Response Rate (ORR)
Objective Response Rate (ORR) of subjects receiving MLN0128 defined as complete response (CR)+partial response (PR), as defined by RECIST v1.1.
Measured: Objective Response Rate is assessed at 16 weeks and 24 weeks from start of treatment cycle until Progressive disease is documented.
Phase I: Disease Control Rate (DCR)
Disease Control Rate (DCR) of subjects receiving MLN0128 as a sum of stable disease (SD for 8 weeks or longer), partial response (PR), and complete response (CR), as defined by RECIST v1.1.
Measured: Disease Control Rate is assessed at 16 weeks and 24 weeks from start of treatment cycle until Progressive disease is documented.
Phase II: Characterize Adverse Effects (AE)
Toxicity for subjects randomized to both MLN0128 and sorafenib arms, assessed using CTCAE v4 criteria
Measured: From date of first dose until 30 days after the last treatment, assessed for estimated 7 cycles (est. 196 days)
Phase II: Radiographic Response Rate (RRR)
Radiographic Response Rate for subjects randomized to both MLN0128 and sorafenib arms, determined utilizing objective response rate (ORR) and disease control rate (DCR) at 16 and 24 weeks.
Measured: Radiographic Response Rate is assessed at 16 weeks and 24 weeks from start of treatment cycle until Progressive disease is documented.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2015 (estimated)
- Study start18 Jul 2016
- Primary completion26 Jun 2018
- Study completion24 Nov 2020
Why it stopped: Funder Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kathy Miller
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Big Ten Cancer Research Consortium
- Responsible party
- Sponsor-investigator, Kathy Miller, Big Ten Cancer Research Consortium
- Investigators
- Kathy D Miller, M.D., Principal investigator, Big Ten Cancer Research Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02575339
- Sponsor's protocol ID
- BTCRC GI13-002
- Status last verified
- Jul 2022
- First submitted
- 9 Oct 2015
- Last updated
- 26 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Randomized Phase I/II Trial of MLN0128 Compared to Sorafenib in Patients With Advanced or Metastatic Hepatocellular Carcinoma: Big Ten Cancer Research Consortium BTCRC-GI13-002
- ClinicalTrials.gov ID
- NCT02575339
- Acronym / sponsor ID
- BTCRC GI13-002
- Conditions
- Hepatocellular Carcinoma, Liver Cancer, HCC
- Keywords
- MLN0128, Sapanisertib, TORC1/2 inhibitor, INK128, Nexavar, Sorafenib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funder Decision
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Kathy MillerUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Big Ten Cancer Research Consortium
- Study start
- 18 Jul 2016 (actual)
- Primary completion
- 26 Jun 2018 (actual)
- Study completion
- 24 Nov 2020 (actual)
- First posted
- 14 Oct 2015 (estimated)
- Results
- Posted 31 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, multi-center, randomized phase I/II study of MLN0128 versus standard sorafenib. Eligible subjects in the phase I trial will receive MLN0128 in escalating doses. Eligible subjects in the phase II trial will be 1:1 randomized to either the MLN0128 arm or the sorafenib arm.
Detailed description
OUTLINE: This is a multi-center trial.
The phase 1 dose escalation trial will evaluate MLN0128 in a standard 3+3 successive cohort design to identify the highest planned dose level. Phase II trial subjects will be 1:1 randomized to receive either MLN0128 (investigational arm) or sorafenib (control arm).
PHASE I DOSE ESCALATION INVESTIGATIONAL TREATMENT:
Cohort 1 (dose level +1) will consist of 3-6 evaluable patients who will receive MLN0128 15mg on day 1 of the 28-day cycle.
Cohort 2 (dose level +2) will consist of 3-6 evaluable patients who will receive MLN0128 20mg on day 1 of the 28-day cycle.
Cohort 3 (dose level +3) will consist of 3-6 evaluable patients who will receive MLN0128 30mg on day 1 of the 28-day cycle.
Subjects will be evaluated for dose limiting toxicity (DLT) in the first 28 days of treatment (1 cycle). However, decisions to move to next dose escalation cohort will not be made until all subjects complete 2 cycles of therapy at a given dose. There will be no further dose escalation beyond dose level +3.
PHASE II INVESTIGATIONAL TREATMENT:
Randomization will take place following completion of the screening evaluations and eligibility assessments. Stratification factors will be employed during randomization to minimize between-arm assignment imbalance.
- 1 Child-Pugh score 5-6
- 2 Child-Pugh score 7
Within the strata, subjects will be randomly assigned with equal probability to either the investigational arm (Arm A: MLN0128) or the control arm (Arm B: sorafenib).
Arm A: MLN0128 will be administered orally at the recommended phase II dose (RP2D) once weekly.
Arm B: Sorafenib will be administered at 400mg PO BID daily, with dose adjustment per standard of care.
A new treatment cycle (1 cycle = 28 days) will only be initiated when all of the following conditions are met:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
- Platelets ≥ 50 x 10*9/L
- Non-hematologic treatment related toxicities have improved to grade 1 or resolved per Common Terminology Criteria for Adverse Events v4.0 (CTCAE)
Treatment may continue until progression, unacceptable toxicity, or withdrawal from study.
Estimated Life Expectancy: ≥ 3 months
Subjects must have adequate organ function, as specified below, within 7 days before study registration:
Bone marrow reserve consistent with:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10*9/L
- Platelet count ≥ 50 x 10*9/L
- Hemoglobin ≥ 9 g/dL
Hepatic:
- Total bilirubin ≤ 2 x upper limit of normal (ULN)
- Transaminases (aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN
Renal:
- Creatinine clearance ≥50 mL/min based either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour)
Metabolic:
- Fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL.
- Glycosylated hemoglobin (HbA1c) <7.0%
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase I MLN0128 Dose Escalation Study | Experimental | Drug: MLN0128Subjects will receive MLN0128 orally on days 1, 8, 15 and 22 in successive cohorts. Cohort 1 MLN0128 15mg each week (QW); Cohort 2 MLN0128 20mg QW; Cohort 3 MLN0128 30mg QW |
| Phase II Arm A: MLN0128 | Experimental | Drug: MLN0128 (RP2D)Subjects randomized to experimental arm will receive MLN0128 orally at the recommended phase II dose (RP2D) once weekly. |
| Phase II Arm B: Sorafenib | Active comparator | Drug: SorafenibSubjects randomized to control arm will receive sorafenib 400mg by mouth (PO) twice a day (BID) daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Male or female subjects 18 years or older at the time of informed consent.
- Voluntary written consent must be signed before performance of any study related procedure not part of standard medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
- Females of childbearing potential must agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
- Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to prior to registration for protocol therapy. NOTE: Female subjects are considered of childbearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Male subjects, even if surgically sterilized (i.e., status post-vasectomy), must agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
Key exclusion criteria (36 listed)
- Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:
- Female subjects who are both lactating and breastfeeding
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Treatment with any investigational products within 28 days prior to study registration.
- No prior systemic treatment is allowed, except for subjects in the phase I cohort who are permitted one prior systemic treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MLN0128Also: SapanisertibPhase I Dose Escalation Study Cohort 1 MLN0128 15mg QW; Cohort 2 MLN0128 20mg QW; Cohort 3 MLN0128 30mg QW | Drug | Phase I MLN0128 Dose Escalation Study |
| MLN0128 (RP2D)Also: SapanisertibPhase II Arm A: MLN0128 administered orally at the recommended phase II dose (RP2D) once weekly. | Drug | Phase II Arm A: MLN0128 |
| SorafenibAlso: NexavarPhase II Arm B: Sorafenib administered at 400mg PO BID daily | Drug | Phase II Arm B: Sorafenib |
Primary outcome
Phase I: Maximum Tolerated Dose (MTD) of MLN0128
Time frame: From start of treatment Day 1 (D1) until completion of two cycles of treatment (maximum 56 days)
The primary objective for phase I of this study is to determine the maximum tolerated dose (MTD) of MLN0128. Maximum Tolerated Dose is defined as the dose level at which fewer than 33% of subjects experience a dose limiting toxicity (DLT).
Phase II: Time to Progression (TTP)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 7 months (estimated).
The primary endpoint of Phase II of the study is to evaluate the time to progression, which is defined as the time from randomization until tumor progression as defined by RECIST v1.1.
10 secondary outcomes
Phase I: Characterize Adverse Effects (AE)
Time frame: From date of first dose until 30 days after the last treatment, assessed for estimated 7 cycles (est. 196 days)
Phase I: Overall Survival (OS) Rate
Time frame: From date of registration until death from any cause, up to a maximum of 27 months
Phase II: Overall Survival (OS) Rate
Time frame: From date of registration until death from any cause, up to a maximum of 24 months
Phase I: Time to Progression (TTP)
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever occurs first, assessed up to 6 months (estimated).
Phase I: Progression-free Survival (PFS)
Time frame: From date of randomization to tumor progression or death from any cause, up to a maximum of 6 months
Phase II: Progression Free Survival (PFS)
Time frame: From date of randomization to tumor progression or death from any cause, up to a maximum of 24 months
Phase I: Objective Response Rate (ORR)
Time frame: Objective Response Rate is assessed at 16 weeks and 24 weeks from start of treatment cycle until Progressive disease is documented.
Phase I: Disease Control Rate (DCR)
Time frame: Disease Control Rate is assessed at 16 weeks and 24 weeks from start of treatment cycle until Progressive disease is documented.
Phase II: Characterize Adverse Effects (AE)
Time frame: From date of first dose until 30 days after the last treatment, assessed for estimated 7 cycles (est. 196 days)
Phase II: Radiographic Response Rate (RRR)
Time frame: Radiographic Response Rate is assessed at 16 weeks and 24 weeks from start of treatment cycle until Progressive disease is documented.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Big Ten Cancer Research Consortium WebsiteLink provided by the sponsor.
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Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy D Miller, M.D. principal investigator
Big Ten Cancer Research Consortium
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MLN0128, MLN0128 (RP2D) and Sorafenib in people with Hepatocellular Carcinoma and Liver Cancer, run by Kathy Miller at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Maximum Tolerated Dose (MTD) of MLN0128 (time frame: From start of treatment Day 1 (D1) until completion of two cycles of treatment (maximum 56 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.