Safety Study Using Weekly Infusions of BB-10901 in Patients With Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study was a Phase I/II trial primarily focused on efficacy of BB-10901 in relapsed small cell lung cancer and other solid tumors.

Detailed Description
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The Phase II efficacy expansion was restricted to SCLC patients with relapsed disease and the MTD was determined by the Phase I portion of the trial (60mg/m2).

Official Title
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A Phase I, Open-Label, Dose Escalation Study of Weekly Dosing With BB-10901, Followed by a Phase II Efficacy Expansion

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: BB-10901


Participation Criteria
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Eligibility Criteria
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Inclusion: Histologically or Cytologically proven SCLC, CD 56+ small cell carcinoma of unknown origin, or CD56+ non-pulmonary small cell carcinoma Relapsed disease; defined as patients with an initial response (partial or complete) to first-line therapy, then relapse more than 3 months after completion of last chemotherapy. Patients must have received no more than 3 prior chemotherapy regimen. Patients must have measurable disease defined as: Lesions that can be measured in at least one dimension according to RECIST Predicted survival of 3 months or more Zubrod performance status 0-2 Patients must not have received chemotherapy or radiation therapy within 4 weeks of study entry, nor have planned surgery. Absolute neutrophils greater than or equal to 1.5 x 10^9/l, hemoglobin greater than or equal to 9g/dl and platelets greater than or equal to 100 x 10^9/l. Creatinine less than or equal to 1.5 times the upper limit of normal AST/ALT less than or equal to 3 times the upper limit of normal without liver metastases; less than or equal to 5 times the upper limit of normal with liver metastases and bilirubin less than or equal to 1.5 times the upper limit of normal. Patients must have normal thyroid function (patients receiving thyroxin replacement therapy who are biochemically euthyroid may be enrolled). Women of childbearing potential must provide a negative pregnancy test at screening and use adequate contraception in the opinion of the investigator, for the duration of study. Patients must be capable of understanding the nature of the trial and must give written witnessed informed consent prior to any screening procedure. Exclusion: Significant residual neurological or cardiac toxicity (grade 3 or 4) following previous chemotherapy Patients who are concurrently receiving other anti-neoplastic treatment (chemotherapy, radiotherapy, or immunotherapy including steroid therapy). Myocardial infarction within 6 months of study entry, unstable angina pectoris, uncontrolled congestive heart failure, uncontrolled arrythmia, severe aortic stenosis, a history of multiple sclerosis, or other demyelinating disease, Eaton-Lambert Syndrome, history of hemorrhagic stroke, any CNS injury with residual neurologic deficit, ischaemic stroke within the last 6 months, current known herpes zoster (shingles), or cytomegalovirus infection, or a history of recurrent infections with these viruses, chronic alcoholism, serious concomitant infection, or any other concomitant illness considered significant enough to interfere with the study outcome. Other investigational agents must not be taken during the study or within 4 weeks of study entry. Previous monoclonal antibody therapy Patients must not have known central nervous system metastases Previous malignancy with < 5 year disease free interval from the last therapeutic intervention, except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix. Patient unwilling or unable to tolerate and comply with the requirements of the study. Pregnant or lactating females.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BB-10901, 5mg/m2 - Phase I<br> | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|
| Experimental: BB-10901, 10 mg/m2 - Phase I<br> | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|
| Experimental: BB-10901, 20 mg/m2 - Phase I<br> | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|
| Experimental: BB-10901, 40 mg/m2 - Phase I<br> | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|
| Experimental: BB-10901, 60 mg/m2 - Phase I & Phase II<br>Phase I and Phase II were consecutive and sequential. Different patients received the 60mg/m2 dose in Phase I and in Phase II. | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|
| Experimental: BB-10901, 67.5 mg/m2 - Phase I<br> | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|
| Experimental: BB-10901, 75 mg/m2 - Phase I<br> | Drug: BB-10901<br>* I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | Dose limiting toxicities graded according to common terminology criteria for advers events, version 2.0 and defined as AEs (probably/definitely related to study drug) meeting the NCI CTC criteria, assessed on the basis of the first cycle of therapy (4 weeks of weekly dosing/2 week fu): Hematologic Tox (Grade 4 neutropenia ≥ 5 days, Grade 4 thrombocytopenia, neutropenic infection); Non-Hem Toxicity: (Any grade 3 or 4 non-hematologic toxicity, excluding nausea, vomiting, diarrhea and alopecia); Toxicity present at Screening (concurrent conditions), an increase in severity of 2 or more grades. | every 6 weeks | 
| Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Response was evaluated by RESIST and Investigator assessment at baseline and every 6 weeks. CR: all target lesions disappear with no clinical or radiographic evidence of disease progression in 2 observations. PR: At least 30% decrease in sum of the longest diameters of target lesions shown in 2 observations. SD: does not qalify for PR or PD based on 2 observations. PD: Either a) the appearance of one or more new lesions, or b) at least a 20% increase in the sum of longest diameters of target lesions | 6 weeks |