Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Mesothelioma

Mesothelioma, Malignant

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Mesothelial

Pleural Neoplasms

Malignant Mesothelioma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Pemetrexed

Cisplatin

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

480 mg orally twice daily (960 mg total daily dose)

BBI608

500 mg/m2 I.V. infusion on Day 1 of each treatment cycle (except for cycle 1, in which Pemetrexed will be given on Day 3).

75 mg/m2 I.V. infusion on Day 1 of each treatment cycle (except for Cycle 1, in which Cisplatin will be given on Day 3).

Sumitomo Pharma Co., Ltd. Japan

This is an open-label, multicenter, phase 1/2 study of BBI608 in combination with pemetrexed and cisplatin chemotherapy as a 1st line treatment for Malignant Pleural Mesothelioma (MPM).

A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

A Phase I/II Clinical Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

An AE is any untoward medical occurrence in a study subject administered an investigational drug and which does not necessarily have a causal relationship with this treatment.

A SAE was an AE that met one or more of the following criteria:

* Results in death
* Is life-threatening
* Requires hospitalization or prolongation of existing hospitalization
* Results in persistent or significant disability or incapacity
* Is a congenital anomaly or birth defect
* Is an important medical event that may jeopardize the subject or may require a medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization.

An ADR was defined as adverse events assessed to be related to the investigational drug

DLT was defined as an adverse event meeting any of the following that occurred during the DLT evaluation period in any participants given BBI608 with the causal relationship to BBI608 assessed as "Definite," "Probable," or "Possible." The severity of adverse events was graded according to the CTCAE v4.0-JCOG.

* Grade 4 neutropenia persisting for ≥ 7 days
* Grade ≥ 3 febrile neutropenia persisting for ≥ 5 days
* Grade 3 thrombocytopenia requiring platelet transfusions, grade 4 thrombocytopenia
* Grade ≥ 3 non-hematotoxicity except the following:

  1. Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment
  2. Diarrhoea and fatigue which, within 5 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment
* Other clinically significant signs in the opinion of the investigator

AUC0-12: Area under the concentration-time curve from time zero to 12 hours, AUC0-24: Area under the concentration-time curve from time zero to 24 hours, AUC0-inf: Area under the concentration-time curve from time zero to infinity

PFS was defined as the time from BBI608 administration to documented PD (as assessed according to the mRECIST or RECIST 1.1) or death, whichever is earlier. The result of imaging assessment by the imaging assessment committee was used for phase 2 part.

The best overall response is the best response recorded from the start of the study treatment until the end of treatment. The RECIST 1.1 was used for the evaluation of tumor response and overall response in patients with NSCLC, and also the evaluation of any non-pleural lesions in patients with MPM. The mRECIST was used for the evaluation of tumor response and overall response in patients with MPM. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part.

Response rate (RR): Proportion of subjects whose best overall response is CR or PR.

Disease control rate (DCR): Proportion of subjects whose best overall response is CR, PR or SD.

The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part.

OS was defined as the time from BBI608 administration to death from any cause. Participants alive at final observation or lost to follow-up were censored at their last contact (i.e., visit or telephone) date.

Sumitomo Pharma Co., Ltd.

Safety analysis population \[separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25)\]

Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles.

Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days.

MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part)

MPM: BBI608 + Pem + CDDP (Phase 2 Part)

MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Primary cancer

Weight

The Eastern Cooperative Oncology Group (ECOG) performance status measures patients' disease status on the following scale: 0=Fully active, able to carry on all pre-disease performance without restriction; 1=Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2=Ambulatory and capable of all selfcare, unable to carry out any work activities. Up and about \>50% of waking hours; 3=Capable of only limited selfcare, confined to bed or chair \>50% of waking hours; 4=Completely disabled. Totally confined to bed or chair; 5=Dead

ECOG PS

NSCLC

Most types of cancer have four stages: stages I (1) to IV (4). Some cancers also have a stage 0 (zero). Lower stages indicate that the disease is more localized, or contained, whereas higher stages refer to cancers that have spread into other areas of the body: Stage 0 = cancer in situ, which means "in place"; Stage I = a small cancer or tumor that has not grown deeply into nearby tissues; Stage II and III = larger cancers or tumors that have grown more deeply into nearby tissue; Stage IV = the cancer has spread to other organs or parts of the body.

Of 4 participants in Phase 1 part, 3 participants with NSCLC and 1 participant with MPM enrolled.

Disease classification

Tissue classification (MPM)

Tissue classification (NSCLC)

Metastases

Disease duration

Participants were NOT enrolled in Phase 1 and Phase 2 in duplicate.

Clinical Research (Oncology)

Any AEs

AEs leading to death

Serious AEs

AEs leading to drug withdrawn (BBI608)

AEs leading to drug interrupted (BBI608)

AEs leading to dose reduced (BBI608)

Any ADRs

ADRs leading to death

Serious ADRs

ADRs leading to drug withdrawn (BBI608)

ADRs leading to drug interrupted (BBI608)

ADRs leading to dose reduced (BBI608)

Safety analysis populations (Phase 1 part)

Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs)

DLT evaluable population (3 participants with NSCLC in Phase 1 part)

1 participant with MPM was excluded from DLT evaluable population because the BBI608 treatment compliance rate during DLT evaluation period did not meet the rate of 80% which of assessable for DLT and no adverse events assessed as DLT occurred.

Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs)

Day 1: Cmax

Day 23: Cmax

Day 23: Cmin

Pharmacokinetic (PK) analysis population

1 participant with MPM of 4 participants in the pharmacokinetic analysis population completed BBI608 administration on Day 14 in Cycle 1 and therefore was not included in the analysis for Cmax and AUC on Day 23.

Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP

Day 1: AUC0-12

Day 1: AUC0-24

Day 1: AUC0-inf

Day 23: AUC0-12

Day 23: AUC0-24

Day 23: AUC0-inf

Phase 1 Part: Area Under the Concentration-time Curve

Participants orally received BBI608(480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days1 in Cycles 2 and subsequent cycles.

Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days.

modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25).

Phase 2 Part: Progression-free Survival (PFS)

NSCLC: BBI608 + Pem + CDDP (Phase 1 Part)

MPM: BBI608 + Pem +CDDP (Phase 1 Part)

MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part)

Best Overall Response

Response rate (RR)

Disease control rate (DCR)

Response Rate (RR) and Disease Control Rate (DCR)

Overall Survival(OS)

The change from baseline in VC: 6 weeks

The change from baseline in VC: 12 weeks

The change from baseline in VC: 18 weeks

The change from baseline in VC: 24 weeks

The change from baseline in VC: 30 weeks

The change from baseline in VC: 39 weeks

The change from baseline in VC: 48 weeks

The change from baseline in VC: 57 weeks

The change from baseline in VC: 66 weeks

The change from baseline in VC: 75 weeks

The change from baseline in VC: 84 weeks

The change from baseline in VC: 93 weeks

The change from baseline in VC: 102 weeks

The change from baseline in VC: 111 weeks

The change from baseline in FVC: 6 weeks

The change from baseline in FVC: 12 weeks

The change from baseline in FVC: 18 weeks

The change from baseline in FVC: 24 weeks

The change from baseline in FVC: 30 weeks

The change from baseline in FVC: 39 weeks

The change from baseline in FVC: 48 weeks

The change from baseline in FVC: 57 weeks

The change from baseline in FVC: 66 weeks

The change from baseline in FVC: 75 weeks

The change from baseline in FVC: 84 weeks

The change from baseline in FVC: 93 weeks

The change from baseline in FVC: 102 weeks

The change from baseline in FVC: 111 weeks

modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). In respiratory function tests, data from 1 participant with MPM in Phase 1 part were not collected.

Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC])

The change from baseline in FEV1: 6 weeks

The change from baseline in FEV1: 12 weeks

The change from baseline in FEV1: 18 weeks

The change from baseline in FEV1: 24 weeks

The change from baseline in FEV1: 30 weeks

The change from baseline in FEV1: 39 weeks

The change from baseline in FEV1: 48 weeks

The change from baseline in FEV1: 57 weeks

The change from baseline in FEV1: 66 weeks

The change from baseline in FEV1: 75 weeks

The change from baseline in FEV1: 84 weeks

The change from baseline in FEV1: 93 weeks

The change from baseline in FEV1: 102 weeks

The change from baseline in FEV1: 111 weeks

Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1])

Overall Study

Spots Global Cancer Trial Database for A Study of BBI608 in Combination With Pemetrexed and Cisplatin in Adult Patients With Malignant Pleural Mesothelioma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial