A Study of HGS1036 in Combination With Chemotherapy in Subjects With Advanced Solid Malignancies

Multi-Center, Open-Label Phase 1B Study to Evaluate the Safety and Tolerability of HGS1036 in Combination With Paclitaxel and Carboplatin, Cisplatin and Etoposide, or Docetaxel in Subjects With Advanced Solid Malignancies

The primary purpose of this study is to determine the maximally tolerated dose (MTD) of HGS1036 when used in combination with the standard chemotherapeutic regimens paclitaxel plus carboplatin, cisplatin plus etoposide, or docetaxel.

Study Overview

• Status: Suspended
• Conditions: Cancer
• Intervention / Treatment: Drug: HGS1036 + Paclitaxel + Carboplatin; Drug: HGS1036 + Cisplatin + Etoposide; Drug: HGS1036 + Docetaxel

Detailed Description

This study will consist of 3 regimens each containing 2 dose levels of HGS1036 and full dose chemotherapy. Patients will be treated in sequence with HGS1036 at planned dose levels of 10 mg/kg and 20 mg/kg. Patients who demonstrate stable disease or better may continue to receive HGS1036 until progressive disease, unacceptable toxicity, patient requests discontinuation of study treatment, or the Investigator feels further treatment is not in the patient's best interest. After discontinuation of HGS1036, subjects will be followed for 30 days after the last dose of HGS1036 for safety. The end of study will be defined as 1 year after the last subject begins treatment of HGS1036. Any subject still receiving HGS1036 at this pre-defined end of study, may continue to receive HGS1036, but the only study assessments required will be for safety.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
  • Massachusetts
    • Boston, Massachusetts, United States, 02114

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:

• Have a histological or cytological diagnosis of malignant solid neoplasm requiring systemic chemotherapy.
• Age ≥18 years.
• ECOG performance status 0-1.
• Adequate organ function.
• Adequate hematological function.
• Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures.
• Consent to collection of previously obtained, archival biopsy or surgical specimens of the currently treated malignancy when available.

Exclusion Criteria:

• Significant cardiac disease.
• Eye trauma or disease.
• Ocular surgery or blunt force trauma to the eye requiring treatment within 3 months prior to first dose of HGS1036.
• Presence or history of ≥ Grade 2 hemoptysis within 2 weeks of the first dose of HGS1036.
• Major surgery within 4 weeks of the first dose of HGS1036.
• Prior organ or allogeneic stem cell transplant.
• Non-healing or chronic wounds.
• Receipt of any anti-cancer therapy within 4 weeks prior to first dose of HGS1036.
• Receipt of any biological therapy (such as monoclonal antibodies) within 6 weeks of the first dose of HGS1036.
• Active CNS involvement by primary or metastatic tumor.
• Documented active infection requiring the use of systemic antibiotics.
• Pregnancy or lactation.
• Known HIV-positive serology, AIDS, or an AIDS-related illness.
• Conditions likely to increase the potential for abdominal perforation or fistula formation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; HGS1036 + Paclitaxel + Carboplatin	Drug: HGS1036 + Paclitaxel + Carboplatin; HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle. Paclitaxel 175 mg/m2 or 200 mg/m2, IV and carboplatin AUC 6.0 mg∙min/mL, IV every 3 weeks on Day 1 of each 21-day cycle.
Experimental: Arm B; HGS1036 + Cisplatin + Etoposide	Drug: HGS1036 + Cisplatin + Etoposide; HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle and cisplatin 60-80 mg/m2, IV on Day 1 and etoposide 100-120 mg/m2, IV on Days 1, 2, and 3 of each 21 day cycle.
Experimental: Arm C; HGS1036 + Docetaxel	Drug: HGS1036 + Docetaxel; HGS1036 10 or 20 mg/kg, IV once weekly in each 21-day cycle and docetaxel 75 mg/m2, IV on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD)	Up to 1 year or longer if indicated.
Number of participants with adverse events	Up to 1 year or longer if indicated.

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc., a GSK Company

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): July 1, 2014

Study Registration Dates

• First Submitted: January 23, 2012
• First Submitted That Met QC Criteria: May 22, 2012
• First Posted (Estimate): May 24, 2012

Study Record Updates

• Last Update Posted (Estimate): November 1, 2012
• Last Update Submitted That Met QC Criteria: October 29, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Cancer; Lung Cancer; Prostate Cancer; Solid Tumors; Mesothelioma; Small Cell lung Cancer
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Docetaxel; Carboplatin; Etoposide; Paclitaxel
• Other Study ID Numbers: HGS1036-C1118