Small Cell Lung Cancer
Conditions
Brief summary
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
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).
Interventions
DRUGBB-10901
I.V. Infusion - See Arms for dosage - Once/Week for three weeks - Until Progression of disease.
Sponsors
ImmunoGen, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | every 6 weeks | 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. |
| Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | 6 weeks | 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 |
Countries
United States
Participant flow
Recruitment details
In Phase I, 32 patients were treated with doses ranging from 5 mg/m2/week to 75 mg/m2/week, with 9 patients treated at the MTD dose of 60 mg/m2/week. In Phase II, 32 advanced cancer patients were treated with BB-10901 at a dose of 60 mg/m2/week. (Total N=64)
Pre-assignment details
This study was an open-label study. All patients that consented to the trial and met inclusion/exclusion criteria were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| IMGN 5 mg/m2 Arm 1, Phase 1 | 4 |
| IMGN 10 mg/m2 Arm 2, Phase 1 | 3 |
| IMGN 20 mg/m2 Arm 3, Phase 1 | 4 |
| IMGN 40 mg/m2 Arm 4, Phase 1 | 4 |
| IMGN 60 mg/m2 Arm 5, Phase 1 and 2 | 41 |
| IMGN 67.5 mg/m2 Arm 6, Phase 1 | 4 |
| IMGN 75 mg/m2 Arm 7, Phase 1 | 4 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Phase II - Apr 2003 - Aug 2008 | Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Phase II - Apr 2003 - Aug 2008 | Lack of Efficacy | 0 | 0 | 0 | 0 | 4 | 0 | 0 |
| Phase I - May 2001 - Oct 2002 | Adverse Event | 0 | 0 | 0 | 1 | 0 | 1 | 2 |
| Phase I - May 2001 - Oct 2002 | Death | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Phase I - May 2001 - Oct 2002 | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Phase I - May 2001 - Oct 2002 | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phase I - May 2001 - Oct 2002 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | IMGN 5 mg/m2 | IMGN 10 mg/m2 | IMGN 20 mg/m2 | IMGN 40 mg/m2 | IMGN 60 mg/m2 | IMGN 67.5 mg/m2 | IMGN 75 mg/m2 | Total |
|---|---|---|---|---|---|---|---|---|
| Age Continuous | 64.0 years STANDARD_DEVIATION 10.86 | 59.0 years STANDARD_DEVIATION 13.08 | 60.0 years STANDARD_DEVIATION 12.65 | 59.8 years STANDARD_DEVIATION 9.07 | 61.2 years STANDARD_DEVIATION 10.1 | 59.5 years STANDARD_DEVIATION 4.8 | 54.5 years STANDARD_DEVIATION 9.5 | 62.67 years STANDARD_DEVIATION 10.01 |
| Age, Customized >=18 years | 4 participants | 3 participants | 4 participants | 4 participants | 41 participants | 4 participants | 4 participants | 64 participants |
| Region of Enrollment United States | 4 participants | 3 participants | 4 participants | 4 participants | 41 participants | 4 participants | 4 participants | 64 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 14 Participants | 1 Participants | 4 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 2 Participants | 3 Participants | 27 Participants | 3 Participants | 0 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 4 | 4 / 4 | 41 / 41 | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 1 / 4 | 0 / 3 | 0 / 4 | 1 / 4 | 5 / 41 | 1 / 4 | 0 / 4 |
Outcome results
Primary
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.
Time frame: every 6 weeks
Population: All Phase I enrolled patients who received study drug were analyzed for DLTs.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Phase I | Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | Headache Grade 3 | 1 participants | — |
| Phase I | Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | Non-infective meningitis | 3 participants | 0 |
| Phase I | Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | Hyperesthesia Grade 4 | 1 participants | — |
| Phase I | Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | Peripheral sensory neuropathy Grade 3 | 1 participants | — |
| Phase I | Phase I Toxicity Based Upon Adverse Events Clasified by the NCI Common Terminology Ctireria Version 2.0 (Phase I) | Fatigue Grade 3 | 1 participants | — |
Primary
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
Time frame: 6 weeks
Population: All patients with a baseline and follow up imaging scan were evaluated. Data represents information following the first cycle of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Stable Disease | 10 participants |
| Phase I | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Progressive Disease (PD) | 16 participants |
| Phase I | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Unknown | 3 participants |
| Phase I | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Complete Response (CR) or Partial Response (PR) | 0 participants |
| Phase II | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Unknown | 0 participants |
| Phase II | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Complete Response (CR) or Partial Response (PR) | 2 participants |
| Phase II | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Stable Disease | 10 participants |
| Phase II | Response Evaluation Criteria in Solid Tumors (RESIST) [Phase I and II] | Progressive Disease (PD) | 17 participants |