Study of Motesanib (AMG 706) in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer

NCT02629848 | Terminated Phase 3 DMC

• 3 other identifiers: TB-AB030103U1111-1176-7347JapicCTI-121887
• Study Type: interventional
• Target: 401
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate progression free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, and safety of motesanib (AMG706) in combination with paclitaxel and carboplatin compared to placebo in combination with paclitaxel and carboplatin.

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  PFS was defined as the time from the date of randomization to the date of disease progression per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death from any cause, whichever occurred first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  Up to 24 Months

Secondary Outcomes (7)

• Overall Survival (OS)

  6, 12, 18 and 24 months

• Objective Response Rate (ORR)

  Up to 30 months

• Duration of Response (DOR)

  Up to 30 months

• Percentage of Participants with Treatment Emergent Adverse Events (TEAEs)

  Up to 30 months

• Percentage of Participants with Abnormal Clinical Laboratory Findings

  Up to 30 months

Study Arms (2)

Motesanib + Paclitaxel + Carboplatin

EXPERIMENTAL

Motesanib 125 mg, (5 x 25 mg) tablets, orally, once daily and paclitaxel 200 mg/m\^2, intravenous, once on Day 1 and carboplatin at a dose to achieve a target Area Under the Curve (AUC) of 6.0 mg/mL x minute, once on Day 1 of a 3 week Cycle for up to 6 Cycles. After 6 Cycles, motesanib 125 mg, tablets, orally, once daily alone until disease progression, drug intolerability, study withdrawal or death for up to 36 months.

Drug: Motesanib; Drug: Paclitaxel; Drug: Carboplatin

Placebo + Paclitaxel + Carboplatin

PLACEBO COMPARATOR

Motesanib placebo-matching tablets, orally, once daily and paclitaxel 200 mg/m\^2, intravenous, once on Day 1 and carboplatin at a dose to achieve a target AUC of 6.0 mg/mL x minute, once on Day 1 of a 3 week Cycle for up to 6 Cycles. After 6 Cycles, motesanib placebo-matching, tablets, orally, once daily alone until disease progression, drug intolerability, study withdrawal or death for up to 36 months.

Drug: Placebo; Drug: Paclitaxel; Drug: Carboplatin

Interventions

Motesanib DRUG

Motesanib (AMG 706) 5 x 25 mg tablets

Also known as: AMG 706

Motesanib + Paclitaxel + Carboplatin

Placebo DRUG

Motesanib placebo-matching tablets

Placebo + Paclitaxel + Carboplatin

Paclitaxel DRUG

Paclitaxel IV

Motesanib + Paclitaxel + Carboplatin; Placebo + Paclitaxel + Carboplatin

Carboplatin DRUG

Carboplatin IV

Motesanib + Paclitaxel + Carboplatin; Placebo + Paclitaxel + Carboplatin

Eligibility Criteria

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

You may qualify if:

• Disease Related:
• Histologically or cytologically confirmed, Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) (except diagnosis by sputum cytology only). Adenosquamous histology or an unclear histology subtype containing more than 10% squamous cells was not allowed.
• No prior chemotherapy, molecularly-targeted therapy, or immunotherapy. Neoadjuvant and post-operative adjuvant therapy except chemotherapy with platinum agent completed 1 year prior to randomization was permitted.
• Measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 criteria (except non-measurable lesion with malignant effusion only).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Life expectancy of ≥ 3 months as documented by the Investigator.
• Demographic:
• Must have been 18 years of age or older at the time informed consent was obtained.
• Laboratory:
• Hematological function, as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L.
• Platelet count ≥ 100 x 10\^9/L and ≤ 850 x 10\^9/L.
• Hemoglobin ≥ 9 g/dL.
• Renal function, as follows:
• Creatinine clearance (GFR) \> 40 mL/min (calculated by Cockcroft-Gault formula).

You may not qualify if:

• Disease Related:
• Symptomatic central nervous system metastases. Participants with asymptomatic brain metastases were eligible if definitive therapy had been administered (surgery and/or radiation therapy), there was no planned treatment for brain metastasis, and the participant was clinically stable and off corticosteroids for at least 2 weeks prior to randomization. Participants with asymptomatic brain metastases were also eligible if the participant did not need definitive therapy (surgery and/or radiation therapy) or corticosteroids according to the Investigator's judgement.
• Palliative radiation therapy:
• Radiation therapy within 28 days prior to randomization for central (chest).
• Radiation therapy within 14 days prior to randomization for distant metastatic foci.
• History of pulmonary hemorrhage or gross hemoptysis (approximately 3 mL of bright red blood or more) within 6 months prior to randomization.
• Medications:
• Prior targeted therapies, including but not limited to:
• AMG 706, inhibitors of vascular endothelial growth factor (VEGF) (eg, SU5416, SU6668, ZD6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib, bevacizumab), or epidermal growth factor receptor (EGFR) (eg, panitumumab, cetuximab, gefitinib, erlotinib).
• Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin (≤ 2 mg daily) or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis was allowed.
• Known history of allergy or hypersensitivity reaction to paclitaxel or carboplatin.
• General:
• History of arterial or venous thrombosis within 12 months prior to randomization.
• History of bleeding diathesis or bleeding within 14 days prior to randomization.
• Peripheral neuropathy ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

motesanib diphosphate; Paclitaxel; Carboplatin

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; Coordination Complexes

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: December 14, 2015
• Study Start: July 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: March 1, 2015
• Last Updated: December 14, 2015

Record last verified: 2015-12