A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)

NCT01100931 | Completed Phase 1 Results

• 2 other identifiers: 10005110-C-0051
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival compared to carboplatin and paclitaxel alone. However, this trial treated only patients with a specific diagnosis and treatment risks. Further research is needed to determine whether this combination is useful for other diagnoses.
• YM155 is a drug that targets a type of chemical often found in cancer cells. It has been investigated in several phase I and phase II clinical trials, and it has been shown to be well tolerated and moderately effective in treating advanced NSCLC in patients who had not responded well to one or two standard treatments. Objectives: \- To determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer. Eligibility: \- Individuals 18 years of age and older who have been diagnosed with advanced non-small-cell lung carcinoma or other solid tumors for which standard therapy is not likely to be effective. Design:
• Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors.
• Participants will be treated for six 21-day cycles, or 18 weeks of treatment. Each cycle will include blood tests and imaging studies as required.
• On day 1 of each cycle, participants will receive an infusion of paclitaxel and carboplatin, followed by a 4-day infusion of YM155 (through a portable electronic infusion pump).
• Participants will have a computed tomography scan or other imaging every other cycle (approximately every 6 weeks) to determine whether the therapy is affecting the cancer site.
• After the sixth cycle, participants will return for follow-up visits at least every 3 months, and will be asked to remain in contact with the researchers to allow further study of the long-term effects of the treatment.

Conditions

NSCLC; Solid Tumors

Keywords

NSCLC; Solid Tumors; YM155; Survivin; Non Small-Cell Lung Cancer; Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Phase 1 Safe and Tolerable Phase 2 Dose.

  Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m\^2, dose level 2:5 mg/m\^2 , dose level 3:6 mg/m\^2, dose level 4:8 mg/m\^2, dose level 5:10 mg/m\^2 (MTD), dose level 6:12 mg/m\^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days). Phase 2 dose is based upon dose limiting toxicities experienced during cycle 1.

  1 year

• Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)).

  Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  up to 18 weeks

• Number of Participants With Adverse Events

  Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

  31.5 months

Study Arms (1)

YM155 in Solid Tumors

EXPERIMENTAL

Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m\^2, dose level 2:5 mg/m\^2 , dose level 3:6 mg/m\^2, dose level 4:8 mg/m\^2, dose level 5:10 mg/m\^2 (MTD), dose level 6:12 mg/m\^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days). Phase II: 10 mg/m\^2 (MTD)intravenous infusion over 72 hours every 21 days.

Drug: YM155; Drug: Carboplatin; Drug: Paclitaxel

Interventions

YM155 DRUG

Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m\^2, dose level 2:5 mg/m\^2 , dose level 3:6 mg/m\^2, dose level 4:8 mg/m\^2, dose level 5:10 mg/m\^2 (MTD), dose level 6:12 mg/m\^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days). Phase II: 10 mg/m\^2 (MTD)intravenous infusion over 72 hours every 21 days.

YM155 in Solid Tumors

Carboplatin DRUG

Area under curve (AUC) of 6 intravenous on day 1

Also known as: Paraplatin

YM155 in Solid Tumors

Paclitaxel DRUG

200 mg/m\^2 intravenous on day 1

Also known as: Taxol

YM155 in Solid Tumors

Eligibility Criteria

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

You may qualify if:

• Response should be YES
• Phase 1 and 2:
• Has a signed consent/assent been obtained by the patient or parent/legal guardian?
• Is a male or female greater than or equal to 18 years old?
• If patient has brain metastases, is it asymptomatic and does not require steroids or antiepileptic mediations?
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky \> 60%)?
• Has adequate bone marrow, renal, and hepatic function:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/m\^3?
• Hemoglobin greater than or equal to 10.0g/dl?
• Platelets greater than or equal to 100,000/m\^3?
• Has adequate renal function defined as serum creatinine \< upper limit of normal (ULN) or calculated creatinine clearance \> 60 mL/min?
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times ULN?
• Total bilirubin less than or equal to 1.5 times ULN (in patients with evidence of Gilberts disease, elevated bilirubin should not be related to tumor or other liver diseases and should be less than or equal 2 times upper limit of normal)?
• Has negative human immunodeficiency virus (HIV) test?
• If female, has negative pregnancy test?

You may not qualify if:

• Response should be NO
• Has any of the following within 6 months prior to study enrollment: myocardial infarction, unstable angina pectoris or uncontrolled angina pectoris, uncontrolled hypertension that is not controllable with antihypertensives, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant peripheral vascular disease (Grade II or greater).
• Has history of stroke or transient ischemic attack within 6 months?
• Has history of pulmonary embolism, deep venous thrombosis or other thrombo-embolic event within 6 months?
• Has psychiatric or neurologic illness that would limit compliance with study requirements?
• Has severe active infection within 14 days requiring use of intravenous antibiotics before beginning treatment?
• Has received any other investigational agents within 30 days of the start of treatment?
• Has history of an active malignancy unless curatively treated and risk of recurrence of \< 5% at five years, with the exception of:
• Adequately treated in situ carcinoma of the cervix
• Non-melanomatous skin cancers (basal or squamous cell)?
• Has history of severe hypersensitivity reaction to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, or medicines of similar composition to YM155?
• Has history of a major surgical procedure, open biopsy, or a significant traumatic injury within 14 days prior to commencing treatment, or the anticipation of the need for a major surgical procedure during the course of the study?
• Has other serious illness, medical condition or significant laboratory abnormality that may cause undue risk for the subject's safety, inhibit protocol participation, or interference with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study?
• Phase 2 only: Has mixed tumor of any histology including small cell lung cancer?

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

  PMID: 17237035 BACKGROUND

• Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954.

  PMID: 11784875 BACKGROUND

• Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, Somerfield MR; American Society of Clinical Oncology. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol. 2004 Jan 15;22(2):330-53. doi: 10.1200/JCO.2004.09.053. Epub 2003 Dec 22. No abstract available.

  PMID: 14691125 BACKGROUND

• Kelly RJ, Thomas A, Rajan A, Chun G, Lopez-Chavez A, Szabo E, Spencer S, Carter CA, Guha U, Khozin S, Poondru S, Van Sant C, Keating A, Steinberg SM, Figg W, Giaccone G. A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013 Oct;24(10):2601-2606. doi: 10.1093/annonc/mdt249. Epub 2013 Jul 14.

  PMID: 23857959 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sepantronium; Carboplatin; Paclitaxel

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)

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

Results Point of Contact

• Title: Dr. Giuseppe Giaccone
• Organization: National Cancer Institute, National Institutes of Health

giacconeg@mail.nih.gov

301-496-4916

Study Officials

• Giuseppe Giaccone, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: April 8, 2010
• First Posted: April 9, 2010
• Study Start: February 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: October 19, 2015
• Results First Posted: April 4, 2013

Record last verified: 2015-09

Locations

US (1)