A Study of Intravenous INO-1001 Plus Oral Temozolomide to Evaluate Tolerability, Safety, and Pharmacokinetics in Patients With Melanoma

A Phase Ib, Open-Label, Multicenter Trial of Intravenous INO-1001 Plus Oral Temozolomide to Evaluate the Tolerability, Safety, and Pharmacokinetics in Subjects With Newly-Diagnosed or Recurrent Unresectable Stage III or Stage IV Melanoma

This is a prospective, open-label, non-randomized, multicenter study in adults, aged eighteen (18) or older, with newly-diagnosed or recurrent unresectable Stage III or Stage IV melanoma. A maximum of 18 subjects will be enrolled in Stage 1 of this study. (Stage 1 completed enrollment in June 2006.) A maximum of 39 subjects will be enrolled in Stage 2 of this study.

Study Overview

• Status: Terminated
• Conditions: Melanoma
• Intervention / Treatment: Drug: INO-1001; Drug: temozolomide

• Study Type: Interventional
• Enrollment (Anticipated): 39
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Biopsy proven malignant melanoma with metastasis that is unresectable Stage III or Stage IV. Subjects with recurrent melanoma that is unresectable are also eligible
• Measurable indicator metastases
• Age 18 years or older
• ECOG status 0-2
• An interval at the time of enrollment of at least: a) 2 weeks since surgical resection (if conducted); b) 4 weeks since prior radiotherapy or chemotherapy, and c) 6 weeks since chemotherapy with a nitrosourea
• Hematocrit > 29%, ANC > 1500 cells/ul, platelets > 100,000 cells/ul
• Serum creatinine within the laboratory's upper limit of normal
• Serum AST and ALT ≤ 1.5 x the laboratory's upper limit of normal
• Subject signed informed consent prior to subject entry

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to administration of each cycle of the study drug regimen.
• Subjects of childbearing potential who are not willing or able to use an effective method of contraception, consisting of at least one-barrier method (e.g., condom and diaphragm), for the duration of the study and for at least 3 months after completing the treatment.
• Subjects previously treated with DTIC or TMZ
• Symptomatic central nervous metastases
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study.
• Confirmed diagnosis of hepatitis or HIV infection
• Any medical, psychiatric, or social problem that might interfere with the performance, completion, and/or interpretation of the trial
• Patients who have had any surgery within two weeks prior to enrollment in this study, or who have not recovered from the side effects of this or any other therapy
• Patients unwilling to comply with the protocol or who in the judgment of the Principal Investigator are unable to abide by the rules of the protocol
• Subjects who have received a potent CYP3A4 inhibitor or inducer orally or parenterally within approximately 14 days prior to enrollment
• Subjects who have received amiodarone within 30 days of study drug administration
• History of hypersensitivity reaction to more than three (3) drugs or to mannitol
• Patients who have received any investigational study agent within 30 days of Day 1 of Cycle 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: INO-1001; Intravenous repeating dose; Drug: temozolomide; Oral repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD) or recommended Phase II dose of INO-1001 to be used in combination with TMZ	Length of study
Pharmacokinetic (PK) profile of intravenous INO-1001	Length of study
Safety and tolerability of combined therapy with oral temozolomide (TMZ) and intravenous INO-1001	Length of study

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Length of study
Safety of repeat dosing	Length of study
Pharmacodynamic (PD) activity of intravenous INO-1001	Length of study
Response	Length of study
Overall survival	Length of study

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Jennifer Low, M.D., Ph.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2005

Study Registration Dates

• First Submitted: January 3, 2006
• First Submitted That Met QC Criteria: January 3, 2006
• First Posted (Estimate): January 6, 2006

Study Record Updates

• Last Update Posted (Estimate): March 11, 2009
• Last Update Submitted That Met QC Criteria: March 9, 2009
• Last Verified: November 1, 2007

More Information

Terms related to this study

• Keywords: Temodar; INO4136g; inotek; Parp
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: IPC-06-2004; INO4136g