Phase 2 N=22 Treatment

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)

NSCLC · Solid Tumors

Bottom Line

View on ClinicalTrials.gov: NCT01100931 ↗

Enrolled (actual)

Serious AEs

26.8%

Results posted

Apr 2013

Primary outcome: Primary: Phase 1 Safe and Tolerable Phase 2 Dose. — 10 mg/m^2

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: YM155 (Drug); Carboplatin (Drug); Paclitaxel (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Dec 2012

Outcome Measures

Outcome	Result	p-value
PRIMARY Phase 1 Safe and Tolerable Phase 2 Dose.	10	—
PRIMARY Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)).	0; 2	—
PRIMARY Number of Participants With Adverse Events	22; 19	—

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.

Eligibility Criteria

INCLUSION CRITERIA:

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 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?
Both male and female patients are willing to consent to using effective contraception (hormonal, barrier method or abstinence) prior to study entry, while on treatment and at least 3 months thereafter?

Phase 1 only:

Has recurrent or advanced cancer for whom standard therapy offers no curative potential and also for patients for whom the carboplatin/paclitaxel regimen is considered standard of care?
Has received no more than one previous chemotherapy regimen?
Has evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria?

Phase 2 only:

Has histological or cytological evidence of non small cell lung cancer?
Has evidence of metastatic disease or stage IIIB non small cell lung cancer (NSCL) with pleural effusion is required?
Has no prior chemotherapy for advanced lung cancer?

Note: Patients who received adjuvant or neo-adjuvant chemotherapy more than 12 months prior will be eligible?

Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan?

EXCLUSION CRITERIA

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

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Data sourced from ClinicalTrials.gov (NCT01100931). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.