Part 2 of Phase 1 Study of GC1008 to Treat Advanced Melanoma (Part 2 Will Only Accept and Treat Patients With Advanced Malignant Melanoma)

NCT00923169 | Completed Phase 1

• 2 other identifiers: 06020006-C-0200
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• GC1008 is a genetically engineered antibody designed to block the activity of transforming growth factor-beta (TGF-beta). Although TGF-beta has some normal and beneficial effects in the body, it is often over-produced in malignant melanoma tumors, and it can help the melanoma grow and spread.
• Part 1 of this study enrolled 22 subjects with malignant melanoma or kidney cancer to determine the highest safe dose of GC1008, which was found to be 15 mg/kg.
• Three of 22 patients with malignant melanoma in Part 1 of the study developed skin problems, but it is not known if these problems were related to the administration of GC1008. Objectives:
• To determine the frequency of adverse skin side effects of GC1008 in patients with malignant melanoma. Eligibility:
• Patients 18 years of age and older with malignant melanoma for whom previous treatment was not successful. Design:
• GC1008 is given intravenously (through a vein) at a dose of 15 mg/kg or 10 mg/kg for four doses on study days 0, 28, 42 and 56 (one treatment cycle). Patients whose cancer responds to GC1008 may receive one or two additional treatment cycles of four doses given every two weeks.
• Physical exam and vital signs on study days 1, 14, 28, 42, 56, 84 and 140.
• Vitals signs on study days 0, 14, 28, 42, 56, 84 and 140.
• Frequent blood sample collections for routine safety tests, measurement of blood levels of GC1008, analysis for antibodies against GC1008 and for research studies.
• CT or MRI scan, bone scan and PET CT scan before treatment and on study day 84 and 140.
• Biopsy of apparently normal skin before treatment and again on day 84.
• Review of medicines and well being on study days 0, 14, 28, 42, 56, 84, 112 and 140.
• Follow-up visits every 3 months for up 2 years for patients who have not received additional treatment for their cancer. Evaluations include physical exam, CT or MRI scan, PET CT scan, blood tests and possibly tumor biopsies.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell; Melanoma; Monoclonal Antibodies; Phase I; TGF-B

Outcome Measures

Primary Outcomes (1)

• To assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and safety of GC1008 in patients with locally advanced or metastatic renal cell carcinoma or malignant melanoma.

Secondary Outcomes (1)

• To obtain pharmacokinetic (PK) and pharmacodynamic (PD) data on GC1008.

Interventions

Anti-Transforming Growth Factor-beta (GC 1008) DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• In Part 1, Dose Escalation: Patients with histologically confirmed, locally advanced and surgically inoperable or metastatic renal cell carcinoma or malignant melanoma are eligible.
• In Part 2, Patient Expansion: Patients with histologically confirmed, locally advanced and surgically inoperable or metastatic malignant melanoma are eligible.
• In both Parts 1 and 2: All patients must have failed greater than or equal to 1 prior therapy and potential patients may not be eligible for curative intent treatment (e.g., potentially curative surgical resection or chemotherapy). Other qualifying therapies include any medical, surgical, radiation, or investigational approach used for potential therapeutic benefit (but not for diagnostic purposes) in patients with advanced disease.
• In addition, in Part 1, patients with renal cell carcinoma must have failed temsirolimus and either sorafenib or sunitinib as part of their prior therapies.
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
• Serum albumin greater than or equal to 3.0 g/dL.
• Expected survival greater than or equal to 5 months.
• Adequate organ function including:
• Marrow: Hemoglobin greater than or equal to 10.0 g/dL, absolute neutrophil count (ANC) greater than or equal to 1,500/mm(3), and platelets greater than or equal to 100,000/mm(3).
• Hepatic: Serum total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) (Patients with Gilberts's Disease may be included if their total bilirubin is less than or equal to 3.0 mg/dL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 2.5 x ULN. If the patient has known liver metastases, an ALT and/or AST less than or equal to 5 x ULN are allowed.
• Renal: If negative proteinuria on urine dipstick, serum creatinine (sCR) less than 2 mg/dL or urine creatinine clearance greater than or equal to 60 mL/min. If urine is 1+ positive (30 mg/dL), urine protein must be less than or equal to 1 g/24 hours and measured creatinine clearance greater than or equal to 60 mL/min.
• Other: Prothrombin time (PT) and partial thromboplastin time (PTT) within normal ranges.
• Measurable disease. Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) within 4 weeks prior to first dose of GC1008 (tumor lesion must be new or progressive if in a previously irradiated region.
• Patients must have negative test (antibody and /or antigen) for hepatitis viruses B and C and human immunodeficiency virus (HIV), unless the result is consistent with prior vaccination or prior infection with full recovery.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Cancer Institute of New Jersey

Little Brunswick, New Jersey, 08901, United States

Location

Related Publications (3)

• Bandyopadhyay A, Zhu Y, Cibull ML, Bao L, Chen C, Sun L. A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells. Cancer Res. 1999 Oct 1;59(19):5041-6.

  PMID: 10519421 BACKGROUND

• Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor beta in human disease. N Engl J Med. 2000 May 4;342(18):1350-8. doi: 10.1056/NEJM200005043421807. No abstract available.

  PMID: 10793168 BACKGROUND

• Derynck R, Akhurst RJ, Balmain A. TGF-beta signaling in tumor suppression and cancer progression. Nat Genet. 2001 Oct;29(2):117-29. doi: 10.1038/ng1001-117.

  PMID: 11586292 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jay A Berzofsky, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: July 9, 2006
• Primary Completion: January 20, 2010
• Study Completion: January 20, 2010
• Last Updated: October 29, 2019

Record last verified: 2012-06-29

Locations

US (1)