Docetaxel With or Without TAK-117 (MLN1117) in Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer

NCT02393209 | Terminated Phase 1 Results

• 3 other identifiers: MLN1117-15012014-004281-25U1111-1160-1736
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 11

Brief Summary

The purpose of this study is to determine the recommended phase 2 dose (RP2D) of TAK-117 when administered in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) and to evaluate efficacy, safety, and tolerability of TAK-117 administered alone and in combination with docetaxel at the RP2D in participants with locally advanced or metastatic non-small cell lung cancer.

Conditions

Non-small Cell Lung Cancer

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b

  DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count \<10,000/mm\^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.

  Cycle 1 (Up to Day 21)

• Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b

  The MTD is defined as the dose of TAK-117 in combination with docetaxel 36 mg/m\^2 at which 1 of 6 evaluable participants experience DLT. DLT was evaluated according to NCI CTCAE version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count \<10,000/mm\^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk.

  Cycle 1 (Up to Day 21)

• Recommended Phase 2 Dose of TAK-117 in Phase 1b

  The recommended phase 2 dose was determined in Phase 1b based on participant dose-limiting toxicities and the maximum tolerated dose.

  Cycle 1 (Up to Day 21)

• Progression-Free Survival (PFS) in Phase 2

  PFS is defined as the time from the date randomization to the date of first documented progressive disease (PD) or death as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease.

  Approximately 12 months in Phase 2

Secondary Outcomes (23)

• Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b

  First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

• Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b

  First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

• Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b

  First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

• Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b

  First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b

  From first dose of study drug to 30 days after last dose of study drug (Up to Day 223)

Study Arms (4)

TAK-117 200 mg + Docetaxel (36 mg/m^2)

EXPERIMENTAL

TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, intravenous (IV) infusion, on Days 1 and 8 of the 21-day cycle up ro Cycle 9 (approximately 189 days).

Drug: Docetaxel; Drug: TAK-117

TAK-117 300 mg + Docetaxel 36 mg/m^2

EXPERIMENTAL

TAK-117 200 mg, tablets, orally on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of the 21-day cycle and docetaxel 36 mg/m\^2, IV infusion, on Days 1 and 8 of the 21-day cycle up to 6 cycles (approximately 126 days).

Drug: Docetaxel; Drug: TAK-117

Phase 2 - TAK-117 + Docetaxel 36 mg/m^2

EXPERIMENTAL

TAK-117 tablets, at the dose determined in the dose escalation phase, on Days 2, 3, 4, 9, 10, 11, 16, 17, and 18 of a 21-day cycle plus Docetaxel 36 mg/m\^2 IV infusion on Days 1 and 8 of a 21-day cycle.

Drug: Docetaxel; Drug: TAK-117

Phase 2 - Docetaxel 75 mg/m^2

EXPERIMENTAL

Docetaxel 75 mg/m\^2, IV infusion once every 3 weeks (per approved prescribing information) with dosing on Day 1 of each 21-day cycle.

Drug: Docetaxel; Drug: TAK-117

Interventions

Docetaxel DRUG

Docetaxel intravenous infusion

Phase 2 - Docetaxel 75 mg/m^2; Phase 2 - TAK-117 + Docetaxel 36 mg/m^2; TAK-117 200 mg + Docetaxel (36 mg/m^2); TAK-117 300 mg + Docetaxel 36 mg/m^2

TAK-117 DRUG

TAK-117 Tablets

Also known as: MLN1117

Phase 2 - Docetaxel 75 mg/m^2; Phase 2 - TAK-117 + Docetaxel 36 mg/m^2; TAK-117 200 mg + Docetaxel (36 mg/m^2); TAK-117 300 mg + Docetaxel 36 mg/m^2

Eligibility Criteria

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

You may qualify if:

• Has a histologically and/or cytologically confirmed diagnosis of NSCLC (squamous or nonsquamous).
• \- For Phase 2 of the study, has a diagnosis of mixed squamous and nonsquamous (or adenosquamous) NSLC.
• Has locally advanced or metastatic disease (Stage IIIb or Stage IV) with radiographically or clinically evaluable lesions.
• Has experienced failure of at least 1 prior chemotherapy regimen:
• For Phase 2 of the study:
• Participants must have received 1 prior platinum-based chemotherapy regimen (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) disease followed by documented progressive disease (PD).
• A drug provided as maintenance therapy following cytotoxic chemotherapy will be considered to be part of that regimen.
• Participants who received prior therapy with paclitaxel as a part of the platinum-based doublet front-line regimen without PD on therapy.
• Participants who, after the front-line, platinum-based, non-docetaxel containing chemotherapy, have been treated with 1 line of nivolumab or other immune-checkpoint inhibitors but progressed on or after the therapy.
• For Phase 1b of the study: Participants who have experienced failure of multiple lines of prior chemotherapy are eligible.
• For Phase 2, has archived or fresh tumor biopsy samples (obtained during screening) sufficient for genotyping.
• Has adequate organ function, before the first dose of study drug.
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Female participants who are postmenopausal for at least 1 year before the screening visit or are surgically sterile, or are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 30 days (or longer, as mandated by local labeling) after the last dose of study drug, or agree to practice true abstinence.
• Female participants must agree to not donate eggs (ova) during the course of this study and for 30 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.

You may not qualify if:

• Previous treatment with a PI3K or AKT inhibitor.
• Prior cancer therapy or other investigational therapy within 2 weeks before the first administration of study drug or failed to recover from the reversible effects of prior anticancer therapies. For prior therapies with a half-life longer than 3 days, the interval must be at least 28 days before the first administration of study drug, and the participant must have documented progressive disease.
• Has poorly controlled diabetes mellitus defined as HbA1c \> 6.5%.
• Has taken strong inhibitors or strong inducers of CYP3A4 within 14 days before the first dose of study drug.
• Has taken histamine-H2 receptor antagonists and/or neutralizing antacids within 24 hours before the first administration of study drug.
• Has taken proton pump inhibitors within 7 days before the first administration of study drug.
• Has a condition that requires the concomitant use of any of the protocol-excluded medications, supplements, or food products during the course of the study .
• Has any clinically significant co-morbidities.
• Has acute myocardial infarction within 6 months before starting study drug, current or history of New York Heart Association Class III or IV heart failure; evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiogram (ECG) evidence of acute ischemia or active conduction system abnormalities; Fridericia's corrected QT interval \> 475 milliseconds (msec) (males) or \> 450 msec (females) on a 12-lead ECG during the Screening period; or abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant.
• Has known, previously diagnosed human immunodeficiency virus infection or active chronic hepatitis B or C.
• Has brain metastasis, unless has completed definitive therapy, is not on steroids, has a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids, and does not have neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Has active secondary malignancy that requires treatment.
• Has any serious medical or psychiatric illness, including drug or alcohol abuse.
• Male participants who intend to donate sperm during the course of this study or 120 days after receiving their last dose of TAK-117 and, for docetaxel, for as long as is mandated by local labeling.
• Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before administration of the first dose of study drug.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (11)

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Farmington Hills, Michigan, United States

Location

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Chattanooga, Tennessee, United States

Location

Unknown Facility

Edmonton, Alberta, Canada

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Hoofddorp, Netherlands

Location

Unknown Facility

Maastricht, Netherlands

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel; serabelisib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2015
• First Posted: March 19, 2015
• Study Start: June 3, 2015
• Primary Completion: January 12, 2017
• Study Completion: January 20, 2017
• Last Updated: February 7, 2018
• Results First Posted: February 7, 2018

Record last verified: 2018-01

Locations

CA (2); US (6); NL (3)