A Study of IMGN901 for Patients With Advanced Solid Tumors and Extensive Stage Small Cell Lung Cancer

NCT ID: NCT01237678

Last Updated: 2018-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2015-05-31

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.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMGN901 with carboplatin and etoposide

Patients will receive IMGN901 along with carboplatin and etoposide for up to 6 cycles and then be able to continue on IMGN901 alone until no further benefit or toxicity.

Group Type: EXPERIMENTAL

IMGN901

Intervention Type: DRUG

Phase 2 regimen is IMGN901, Carboplatin, and Etoposide. IMGN901 to be given on days 1 and 8 every 21 days.

Carboplatin and Etoposide

Patients will receive Carboplatin and etoposide for up to 6 cycles.

Group Type: ACTIVE_COMPARATOR

Carboplatin and Etoposide

Intervention Type: DRUG

Patients assigned to Arm 2 were to receive carboplatin at the same AUC as utilized in Arm 1

Interventions

IMGN901

Phase 2 regimen is IMGN901, Carboplatin, and Etoposide. IMGN901 to be given on days 1 and 8 every 21 days.

Intervention Type: DRUG

Carboplatin and Etoposide

Patients assigned to Arm 2 were to receive carboplatin at the same AUC as utilized in Arm 1

Intervention Type: DRUG

Other Intervention Names

BB-10901, Lorvotuzumab mertansine; Toposar®, VePesid®, Etopophos®

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ImmunoGen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arizona Cancer Center @ UMC North

Tucson, Arizona, United States

UCLA Oncology Center

Los Angeles, California, United States

St. Joseph's Hospital

Orange, California, United States

UCLA Hematology

Pasadena, California, United States

UCLA Oncology Clinic

Santa Monica, California, United States

UCLA Santa Clarita Valley Cancer Center

Valencia, California, United States

UCLA Oncology Center

Westlake Village, California, United States

Yale Medical Center

New Haven, Connecticut, United States

Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Holy Cross Hospital Bienes Comprehensive Cancer Center

Fort Lauderdale, Florida, United States

University of Florida

Gainesville, Florida, United States

Anne Arundel Medical Center

Annapolis, Maryland, United States

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Bayview Medical Center

Baltimore, Maryland, United States

Johns Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Johnson Therurer Cancer Center at Hackensack

Hackensack, New Jersey, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Oklahoma University

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

UPMC Cancer Centers East, Oxford Drive

Monroeville, Pennsylvania, United States

UPMC Cancer Center St. Margaret

Pittsburgh, Pennsylvania, United States

Univeristy of Pittsburg Medical Center

Pittsburgh, Pennsylvania, United States

UPMC Cancer Center at UPMC Passavant (HOA)

Pittsburgh, Pennsylvania, United States

South Carolina Oncology Associates

Columbia, South Carolina, United States

University of Tennessee Medical Center Cancer Institute

Knoxville, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

UTHSC at San Antonio

San Antonio, Texas, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Juravinski Cancer Center

Hamilton, Ontario, Canada

Montreal General Hospital

Montreal, Quebec, Canada

Jewish General Hospital

Montreal, Quebec, Canada

St. Mary's Hospital

Montreal, Quebec, Canada

Royal Victoria

Montreal, Quebec, Canada

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital de la Santa Creu y Sand Pau

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Royal Sussex Hospital

Brighton, East Sussex, United Kingdom

University College of London

London, England, United Kingdom

The Christie Hospital

Withington, Manchester, United Kingdom

Royal Marsden

Sutton, Surrey, United Kingdom

Royal Marsden, London

London, , United Kingdom

Countries

United States; Canada; Spain; United Kingdom

Other Identifiers

Immunogen 0007

Identifier Type: -

Identifier Source: org_study_id