Dose Escalation Study of MLN0128 in Participants With Advanced Malignancies

Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase I, Open Label, Dose Escalation Study of Oral Administration of Single Agent INK128 in Subjects With Advanced Malignancies Followed by an Expansion in Subjects With Measurable Disease

ClinicalTrials.gov ID

NCT01058707

Acronym / sponsor ID

INK128-001

Conditions

Advanced Solid Malignancies

Keywords

Solid tumors, MLN0128, TORC1/2 inhibitors

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

198 participants (actual)

Lead sponsor

Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)

Study start

4 Jan 2010 (actual)

Primary completion

7 Feb 2019 (actual)

Study completion

7 Feb 2019 (actual)

First posted

29 Jan 2010 (estimated)

Results

Posted 1 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

7

Model description

The Escalation Phase was sequential and the Expansion Phase was parallel.

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Dose Escalation Phase: Maximum Tolerated Dose (MTD)

   Time frame: Cycle 1 (28 Days)

   MTD was defined as the highest dose level of MLN0128 at which no more than 1 out of 6 evaluable participants experienced a DLT during the first cycle (28 days) of therapy.

2. Dose Escalation Phase: Number of Participants With Dose Limiting Toxicities (DLTs)

   Time frame: Cycle 1 (28 days)

   DLTs were defined as MLN0128-related treatment-emergent adverse events (TEAEs) that occurred within the Cycle 1 (first 28 days of treatment) as per Common Terminology Criteria for Adverse Events (CTCAE): Any ≥Grade 3 or non-hematologic toxicity except for Grade 3 nausea and/or vomiting and diarrhea, Grade 3 hyperglycemia lasting ≤ 14 days, Grade 3 rash lasting ≤ 3 days; Grade 4 neutropenia lasting >7 days in the absence of growth factor support; Grade 4 neutropenia of any duration associated with fever ≥38.5 degree celsius and/or systemic infection; Any other Grade 4 hematologic toxicity; Inability to administer at least 75% of planned doses of MLN0128 within Cycle 1 due to drug-related toxicity and any clinically significant occurrence that the investigators and sponsor agreed would place participants at an undue safety risk.

3. Number of Participants Experiencing One or More Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Resulting in Discontinuation of MLN0128 and Fatal AEs Within 30 Days of Last Dose of Study Drug

   Time frame: First dose of study drug through 30 days after the administration of the last dose of study drug (Up to approximately 244 weeks)

   An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

4. Dose Expansion: Objective Response Rate (ORR)

   Time frame: From the first dose of study drug up to disease progression or death (Up to approximately 240 weeks)

   ORR is defined as the percentage of participants who achieved complete response (CR) or partial response (PR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR is defined as disappearance of all target lesions and PR was defined of at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions. Data was categorized as per type of cancer.

5. Dose Expansion Phase: Duration of Objective Response

   Time frame: From the first dose of study drug up to disease progression or death (Up to approximately 240 weeks)

   Duration of objective response is defined as the number of months from the start date of CR or PR (whichever occurred first) based on RECIST Criteria version 1.1 to the first date of objectively documented progressive disease (PD) for participants who achieved CR or PR. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

6. Dose Expansion: Duration of Stable Disease (SD)

   Time frame: From the first dose of study drug up to disease progression or death (Up to approximately 240 weeks)

   Duration of SD was evaluated for participants with best response of SD and is defined as number of months from date of first dose to date of PD. As per RECIST 1.1, SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR was defined of at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD and for non-target lesions. PD is defined as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this includes baseline sum if that is smallest on study).

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2020.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 32913286Voss MH, Gordon MS, Mita M, Rini B, Makker V, Macarulla T, Smith DC, Cervantes A, Puzanov I, Pili R, Wang D, Jalal S, Pant S, Patel MR, Neuwirth RL, Enke A, Shou Y, Sedarati F, Faller DV, Burris HA 3rd. Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer. Br J Cancer. 2020 Nov;123(11):1590-1598. doi: 10.1038/s41416-020-01041-x. Epub 2020 Sep 11.
• Individual participant dataSharing planned: Yes. Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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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.

16 sites in 2 countries: see every site and its status.