NCT02503722

Brief Summary

This phase I trial studies the side effects and best dose of sapanisertib when given together with osimertinib in treating patients with stage IV EGFR mutation positive non-small cell lung cancer that has progressed after treatment with an EGFR tyrosine kinase inhibitor. Sapanisertib and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P50-P75 for phase_1

Timeline
9mo left

Started Mar 2017

Longer than P75 for phase_1

Geographic Reach
2 countries

5 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress93%
Mar 2017Feb 2027

First Submitted

Initial submission to the registry

July 20, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 21, 2015

Completed
1.7 years until next milestone

Study Start

First participant enrolled

March 23, 2017

Completed
9.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2027

Last Updated

June 11, 2026

Status Verified

June 1, 2026

Enrollment Period

9.9 years

First QC Date

July 20, 2015

Last Update Submit

June 10, 2026

Conditions

Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Non-Small Cell Cancer AJCC v7Metastatic Lung Non-Small Cell CarcinomaStage III Lung Non-Small Cell Cancer AJCC v7Stage IIIA Lung Non-Small Cell Cancer AJCC v7Stage IIIB Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

  • Maximum tolerated dose of sapanisertib in combination with osimertinib in patients with EGFRmutant (m) non-small cell lung cancer (NSCLC)

    Toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). CTCAE version 5.0 will be utilized beginning April 1, 2018.

    28 days

  • Dose-limiting toxicity (DLT) of sapanisertib in combination with osimertinib in patients with EGFRm NSCLC

    Toxicities will be graded according to the NCI CTCAE v4. CTCAE version 5.0 will be utilized beginning April 1, 2018.

    28 days

Secondary Outcomes (9)

  • Non-DLTs associated with the administration of sapanisertib and osimertinib

    Up to 30 days after completion of study treatment

  • Pharmacokinetic (PK) profiles of sapanisertib in combination with osimertinib

    Baseline, and at 1, 2, 4, 6, 8, and 24 hours post-sapanisertib administration, before administration and at 1, 2, 4, 6, 8, and 24 hours post-sapanisertib on day 26 of course 1; and day 1 of course 2

  • Response rate

    Up to 2 years

  • Disease control rate

    Up to 2 years

  • Progression free survival

    From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

  • +4 more secondary outcomes

Study Arms (1)

Treatment (sapanisertib, osimertinib)

EXPERIMENTAL

Patients receive sapanisertib PO QD on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 (day 1 is omitted in cycle 1). Patients also receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker AnalysisDrug: OsimertinibOther: Pharmacological StudyDrug: Sapanisertib

Interventions

OsimertinibDRUG

Given PO

Also known as: AZD 9291, AZD-9291, AZD9291, Mereletinib
Treatment (sapanisertib, osimertinib)
Pharmacological StudyOTHER

Correlative studies

Treatment (sapanisertib, osimertinib)
Laboratory Biomarker AnalysisOTHER

Correlative studies

Treatment (sapanisertib, osimertinib)
SapanisertibDRUG

Given PO

Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228
Treatment (sapanisertib, osimertinib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with stage IV or recurrent/metastatic histologically or cytologically confirmed non-squamous NSCLC
  • NSCLC must harbor an EGFR activating mutation (Exon 21 L858R, Exon 19 deletion)
  • Progressive disease on osimertinib (AZD9291) given first line
  • For the dose expansion portion ONLY, patient must: 1) have progression of disease with first line osimertinib administered for advanced or metastatic disease as the last previous systemic treatment, 2) be treatment naïve for other 3rd generation EGFR-TKI (CO-1686) and mTOR inhibitors
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at least one dimension \>= 10 mm (\>= 1 cm) by computed tomography (CT) imaging or magnetic resonance imaging (MRI) within 28 days prior to start of protocol therapy; the CT from a combined positron emission tomography (PET)/CT may be used if it is of diagnostic quality; laboratory parameters are not acceptable as the only evidence of disease
  • For the dose expansion, no other systemic therapies for advanced/metastatic disease is permissible after first line osimertinib
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
  • Patients with a prior history of brain metastases are eligible provided:
  • The brain metastases have been treated; patients with small brain metastases for which radiation or surgery is not indicated, may be eligible on discussion with the study chair. Brain metastases that were managed with first line osimertinib is permissible, provided that the brain metastases are stable on a baseline MRI and for whom radiation or surgical resection is not indicated
  • The patient is asymptomatic from the brain metastases
  • Corticosteroids and anti-epileptic drugs prescribed for the management of brain metastases have been discontinued at least 7 days prior to registration
  • The brain metastases are stable on pre-registration imaging
  • Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
  • Hemoglobin \>= 90 g/L (or \>= 9 g/dL)
  • Platelets \>= 100 x 10\^9/L
  • +16 more criteria

You may not qualify if:

  • Any serious intercurrent or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol including but not limited to:
  • Uncontrolled diabetes mellitus (fasting plasma glucose \> 130 mg/dL or 7.2 mmol/L)
  • Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
  • Active infections
  • Gastrointestinal disease limiting the ability to swallow oral medications or absorb oral medications including refractory nausea and vomiting, chronic gastrointestinal diseases, inflammatory bowel disease; malabsorption syndromes
  • Patients with enteric stomata or significant bowel resection
  • Prior history of corneal ulceration
  • Patients with any evidence of severe or uncontrolled systemic liver disease including those with known hepatitis B and hepatitis C (excluding treated hepatitis C that has been cured)
  • Active bleeding diatheses
  • Significant active cardiovascular or pulmonary disease including:
  • Uncontrolled hypertension (i.e., systolic blood pressure \> 180 mmHg, diastolic blood pressure \> 95 mmHg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed
  • Pulmonary hypertension
  • Uncontrolled asthma or oxygen (O2) saturation \< 90% by 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
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG) e.g. medically significant (symptomatic) bradycardia, complete left bundle branch block, third degree heart block and second-degree heart block or history of arrhythmia requiring an implantable cardiac defibrillator; or within the last 6 months before administration of the first dose of drug:
  • +28 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinibsapanisertib

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Study Officials

  • Penelope A Bradbury

    University Health Network Princess Margaret Cancer Center LAO

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 20, 2015

First Posted

July 21, 2015

Study Start

March 23, 2017

Primary Completion (Estimated)

February 28, 2027

Study Completion (Estimated)

February 28, 2027

Last Updated

June 11, 2026

Record last verified: 2026-06

Locations

CA(2)US(3)