Clinical trial NCT01237678: A Study of IMGN901 for Patients With Advanced Solid Tumors and Extensive Stage Small Cell Lung Cancer
Official title: A Phase 1/2 Study to Assess the Safety and Efficacy of Lorvotuzumab Mertansine in Combination With Carboplatin/Etoposide in Patients With Advanced Solid Tumors Including Extensive Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Small Cell Lung Cancer
Keywords: Immunogen
Lung
Small Cell Lung Cancer
Carboplatin
ADC
Lead sponsor: ImmunoGen, Inc.
Sponsor class: INDUSTRY
First posted: 2010-11-09
Enrollment: 181
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to test safety and efficacy of this combination treatment (IMGN901, carboplatin and etoposide) in patients with solid tumors and extensive stage small cell lung cancer.

Detailed description: Small-Cell Lung Cancer (SCLC) is a neuroendocrine cancer of the lung that is typically caused by smoking. Patients generally present with symptoms of cough, dyspnea, pain and weakness, and often have extensive disease at that time. It is estimated that 13% of lung cancers are SCLC in origin1. Approximately 28,530 new cases of SCLC were expected in 2009 based on an estimate of 219,440 new cases of any cancer of the lung in the US in 20092.

There are 2 stages of the disease: limited-stage disease (LD) and extensive-stage disease (ED). SCLC-LD is confined to a region of the chest (the hemithorax and mediastinum) that is more amenable to radiation therapy. Thirty percent (30%) of patients present with SCLC-LD. The remaining patients (70%) present with SCLC-ED, in which the disease has progressed outside this region of the chest. Common sites of metastatic disease include the contralateral lung, liver, adrenal glands, brain, bones and/or bone marrow3. Recurrence after therapy is typical. In the rare patient who has longer-term survival, secondary malignancies (new SCLC tumors and other malignancies) are common because of long-term exposure to carcinogens.

SCLC is very responsive to chemotherapy and radiation therapy, having response rates of up to 80%4-7. In limited stage disease, the standard treatment is 'combined-modality therapy' consisting of combination chemotherapy such as cisplatin plus etoposide followed by thoracic radiation therapy. Surgery is rarely used.

Despite high response rates, therapy is rarely curative due to high rates of recurrence and metastasis. Overall 5-year survival for SCLC patients is 4%5. SCLC-LD patients typically achieve median survival of 14 to 24 months after therapy, with a 2-year survival rate of 40% to 50%. This survival rate drops to about 20% at 5 years4-7. SCLC-ED patients achieve a median survival of 8 to 12 months on therapy8.

Patients will typically have recurrent disease after therapy. While many of these patients may be eligible for further chemotherapy, survival at this stage is usually less than 6 months.

No treatment modality has a significant impact on overall survival. Studies utilizing regimens with greater numbers of chemotherapeutic agents or longer therapy duration have not improved survival. Thus, a new therapy that can improve survival is needed.

IMGN901 is an antibody drug conjugate which is anticipated to result in lower systemic toxicity and greater efficacy than currently available therapies based on its specific and high affinity binding to its target antigen, CD56. This antigen has been shown to be present in almost all cases of SCLC (\~ 95% based on in-house data). In in vivo studies, IMGN901 has demonstrated potent anti-tumor activity against CD56-positive carcinomas including xenograft models of SCLC as well as complete regressions when combined with cisplatin/etoposide. Preliminary clinical activity of single agent IMGN901 based on data from two Phase 1 studies shows a disease control rate (PR and SD, defined as non-progression for at least 75 days) estimated to be 24% in a heterogeneous population of patients with pretreated and drug resistant SCLC. Additional data supportive of the potential activity of IMGN901 includes complete responses and clinically relevant stable disease in patients with MCC (clinical benefit rate = 39%). Further, the tolerability profile demonstrating minimal myelosuppression with administration of IMGN901 is supportive of exploring its use in combination with established chemotherapy regimens.

IMGN901 is supportive of exploring its use in combination with established chemotherapy regimens.

Therefore, the Phase 1 portion of this study is designed to first determine the MTD, presumably the recommended Phase 2 dose, of IMGN901 when administered in combination with carboplatin/etoposide treatment and to characterize the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity of this triplet combination.

Improvement in disease control and survival of patients with SCLC-ED remains a major therapeutic challenge. New agents with better activity and tolerability are needed for this population. However, because large-scale clinical studies often are necessary to demonstrate the safety and effectiveness of these new agents, it is desirable to first evaluate some measure of relative effectiveness in a Phase 2 study.

Therefore the Phase 2 portion of the study will utilize a Simon two-stage design in which the activity of IMGN901 will be assessed by comparing the PFS rate at six months in the IMGN901 experimental arm (triplet combination) against the historical 6 month PFS rate of 0.44 (equivalently a median PFS = 5 months). In this study, an improvement of 2.5 months in median PFS will be deemed clinically relevant and correlates to a PFS rate of 0.58 (HR = 0.667). The control arm will be used primarily to reliably assess the safety of IMGN901 and will further serve as an informal validation of the historical data.

Eligibility criteria: Inclusion Criteria:

* Patients must be 18 years old
* Patients must have been diagnosed with small-cell lung cancer (SCLC) and extensive disease
* ECOG performance status of 0, 1, or 2
* No prior systemic chemotherapy for the treatment of SCLC

Exclusion Criteria:

- Pregnant or lactating females

Primary outcomes:
measure: Occurrence of Dose Limiting Toxicities (DLT)
timeFrame: 21 days (Cycle 1)
measure: Progression Free Survival (PFS) in Phase II
timeFrame: From randomization to objective tumor progression or death (up to post-treatment follow-up 28 days after last dose, up to 22 months)
measure: Maximum Tolerated Dose (MTD) of IMGN901
timeFrame: 21 days (Cycle 1)
Secondary outcomes:
measure: Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose of study drug on Cycle 1, Day 1 until 28 days after the last study treatment (up to 22 months)
measure: Progression Free Survival (PFS) Rate at 6 Months
timeFrame: 6 months
measure: Median Overall Survival (OS) in Phase II
timeFrame: From the time of enrollment until death on study due to any cause (up to post-treatment follow-up 28 days after last dose, up to 22 months)
measure: Overall Survival (OS) Rate at 12 Months
timeFrame: 12 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center @ UMC North
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Oncology Center
state: California
city: Orange
country: United States
facility: St. Joseph's Hospital
state: California
city: Pasadena
country: United States
facility: UCLA Hematology
state: California
city: Santa Monica
country: United States
facility: UCLA Oncology Clinic
state: California
city: Valencia
country: United States
facility: UCLA Santa Clarita Valley Cancer Center
state: California
city: Westlake Village
country: United States
facility: UCLA Oncology Center
state: California
city: New Haven
country: United States
facility: Yale Medical Center
state: Connecticut
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital Bienes Comprehensive Cancer Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: Johnson Therurer Cancer Center at Hackensack
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Monroeville
country: United States
facility: UPMC Cancer Centers East, Oxford Drive
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center St. Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univeristy of Pittsburg Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC Passavant (HOA)
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Cancer Institute
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: UTHSC at San Antonio
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Hamilton
country: Canada
facility: Juravinski Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: St. Mary's Hospital
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria
state: Quebec
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu y Sand Pau
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Brighton
country: United Kingdom
facility: Royal Sussex Hospital
state: East Sussex
city: London
country: United Kingdom
facility: University College of London
state: England
city: Withington
country: United Kingdom
facility: The Christie Hospital
state: Manchester
city: Sutton
country: United Kingdom
facility: Royal Marsden
state: Surrey
city: London
country: United Kingdom
facility: Royal Marsden, London
Study officials:
References: