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Pilot Study to Evaluate the Effects of a Vaccine (HSPPC-96) Combined With Ipilimumab in Patients With Advanced Melanoma

Primary Purpose

Melanoma

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ipilimumab

HSPPC-96

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Therapeutically Unresectable, Stage III or Stage IV, Malignant Melanoma, Advanced Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:Pre-surgery Inclusion criteria:

Signed informed consent
≥ 18 years of age
Stage III or Stage IV melanoma according to TNM staging criteria/AJCC version 7 determined by PET/MRI/CT scan
ECOG score 0 or 1
Life expectancy ≥6 months
Candidate for surgical resection with viable melanoma tissue to ascertain ≥ 7 grams of viable cancer tissue (in aggregate), which is equivalent to a ≥ 2 cm lesion on CT/MRI or clinical examination
Adequate cardiac function (≤ NYHA class II)
Adequate bone marrow function, including: absolute granulocyte count (ANC) ≥ 1,500x106/L, absolute lymphocyte count (ALC) ≥ 500/mm3, platelets count ≥100,000 x 106/mm3. Adequate liver function including: serum glutamic oxaloacetic transaminases/aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the upper limit of institutional normal (IULNs), bilirubin ≤ 1.5 mg/dL or 25 µmol/L (SI units). Adequate renal function: BUN and Serum creatinine of ≤ 1.5 mg/dL or 130 µmol/L (SI units)
Female subjects of childbearing potential and fertile males must agree to use adequate contraception during the course of the study. Adequate contraception includes condoms with contraceptive foam; oral, implantable or injectable contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal gel; or a sexual partner who is surgically sterilized or postmenopausal.
- Post-surgery Inclusion Criteria (must be completed within 4 weeks of surgery)
Histologically and clinically confirmed Stage III and/or Stage IV malignant melanoma according to TNM Staging Criteria/AJCC version 7 confirmed by PET/CT scan
Measurable disease for target lesion clinical and radiological monitoring
ECOG score 0 or 1
Adequate cardiac function (≤ NYHA class II)
Adequate bone marrow function, liver, and renal function
≥ 6 doses of vaccine for clinical use

Exclusion Criteria: Pre-Surgery Exclusion Criteria:

Primary mucosal or primary ocular melanomas
Other malignancies treated within the last five years, except in situ cervix carcinoma or non-melanoma skin cancer
Primary or secondary immunodeficiency (including immunosuppressive disease, or systemic use of corticosteroids or other immunosuppressive medications)
Patients with history of HIV1 and 2, HTLV-1, HBV or active HCV.
Patients with history of connective tissue disorders
Prior ipilimumab or melanoma vaccine therapy
Prior therapy with IL-2
Prior chemotherapy, small molecule targeted therapy, interferon within 3 months prior to enrollment
Prior investigational products administration within 4 weeks prior to enrollment
Prior splenectomy
Symptomatic CNS metastases or spinal cord compression
Uncontrolled infection or other serious medical illnesses
Any medical conditions that, in the opinion of the investigator, would preclude use of ipilimumab, including ipilimumab hypersensitivity
Women who are pregnant or breast-feeding
Concurrent participation in investigational trials
- Post-surgery Exclusion Criteria (must be completed within 4 weeks of surgery):
Emergence of contraindicated clinical condition

Sites / Locations

UTHealth Memorial Hermann Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ipilimumab + HSPPC-96

Arm Description

Ipilimumab is administered intravenously at a dose of 3 mg/kg one day (a minimum of 12 hours and not more than 48 hours) before HSPPC-96 every 21-25 days for a total of 4 cycles. HSPPC-96 is administered at a dose of 25 μg by intradermal injection always 12 - 48 hours following ipilimumab on a weekly basis for the first 4 weeks and then every 3 weeks always 12 - 48 hours after ipilimumab. Length of Treatment: 4 cycles of ipilimumab and at least 6 cycles of HSPPC-96 up to 12 doses. Booster doses of HSPCC-96 following 6 administrations on subsequent cycles will be administered every 21-23 days according to availability of vaccine.

Outcomes

Primary Outcome Measures

All enrolled patients who receive at least one dose of study drug (HSPPC-96) will be evaluated for safety. (adverse events)

AEs will be coded by system organ class and preferred term using MedDRA. AEs will be summarized using descriptive statistics. Descriptive statistics will contain the number and percentage of patients who experience at least 1 AE, AEs related to study treatment, SAEs, SAEs related to study treatment, grade 3, 4 or 5 AEs, and grade 3, 4 or 5 AEs related to study treatment. In addition, the number and percentage of patients who discontinue treatment for any reason, including discontinuation due to an AE, will be provided together with the number and percentage of patients who die.

• To assess immunological response by surrogate markers of immune response and modulation of tumor cellular microenvironment

All enrolled patients who receive at least one full cycle of treatment and have a baseline and at least one post treatment biological specimen available (tissue and/or blood) will be evaluated for immune response.

Secondary Outcome Measures

Objective Response Rate (ORR)

ORR defined by complete and partial responses.

Progression Free Survival (PFS)

Time to recurrence is time from surgery until recurrence or last tumor evaluation without recurrence.

Full Information

NCT ID

NCT02452281

First Posted

May 13, 2015

Last Updated

January 22, 2016

Sponsor

Rabih Said

Collaborators

Agenus Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02452281

Brief Title

Pilot Study to Evaluate the Effects of a Vaccine (HSPPC-96) Combined With Ipilimumab in Patients With Advanced Melanoma

Official Title

Phase I-II Pilot Study to Evaluate the Immune-mediated Effects of an Autologous Tumor-derived Heat Shock Protein-peptide Complex 96 (HSPPC-96) Combined With Ipilimumab in Patients With Therapeutically Unresectable Stage III or Stage IV Malignant Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Withdrawn

Why Stopped

PI departure, operational issues

Study Start Date

December 2015 (undefined)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

December 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Rabih Said

Collaborators

Agenus Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this research study is to see if the combination of HSPPC-96 and ipilimumab is safe and effective in the treatment of advanced melanoma. HSPPC-96 is an investigational vaccine created from tissue from the patient's tumor. The vaccine is designed to capture the cancer's "fingerprint." Injection of the vaccine may cause the patient's immune system to recognize and attack any cells with the specific cancer fingerprint. Ipilimumab is a drug approved by the FDA for the treatment of metastatic melanoma that boosts immune response.

Detailed Description

This is a randomized, open label, single-center, phase I-II trial to determine the safety, feasibility and immunogenicity of combination treatment of HSPPC-96 and ipilimumab in patients with therapeutically unresectable Stage III or Stage IV malignant melanoma. The main purpose of this study is to assess whether the administration of the combination of ipilimumab and HSPPC-96 is safe. The rationale for combining the two treatments resides in their respective roles on the immune system as described below and based on the clinical experience collected so far. HSPPC-96 is able to initiate a tumor specific immune response that ipilimumab could theoretically amplify by blocking a checkpoint that naturally down-regulates T cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

Therapeutically Unresectable, Stage III or Stage IV, Malignant Melanoma, Advanced Melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ipilimumab + HSPPC-96

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

ipilimumab

Other Intervention Name(s)

Yervoy ®

Intervention Description

3 mg/kg, IV one day (a minimum of 12 hours and not more than 48 hours) before HSPPC-96 every 21-25 days for a total of 4 cycles.

Intervention Type

Drug

Intervention Name(s)

HSPPC-96

Other Intervention Name(s)

heat shock protein-peptide complex 96; Prophage; Vitespen

Intervention Description

25 μg by intradermal injection always 12 - 48 hours following ipilimumab on a weekly basis for the first 4 weeks and then every 3 weeks always 12 - 48 hours after ipilimumab; for at least 6 cycles of HSPPC-96 up to 12 doses.

Primary Outcome Measure Information:

Title

All enrolled patients who receive at least one dose of study drug (HSPPC-96) will be evaluated for safety. (adverse events)

Description

Time Frame

2 years

Title

• To assess immunological response by surrogate markers of immune response and modulation of tumor cellular microenvironment

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Objective Response Rate (ORR)

Description

ORR defined by complete and partial responses.

Time Frame

tumor evaluations every 12 weeks or until the date of first documented progression or death, whichever came first, assessed up to 24 months

Title

Progression Free Survival (PFS)

Description

Time to recurrence is time from surgery until recurrence or last tumor evaluation without recurrence.

Time Frame

tumor evaluations every 12 weeks or until the date of first documented progression or death, whichever came first, assessed up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria:Pre-surgery Inclusion criteria: Signed informed consent ≥ 18 years of age Stage III or Stage IV melanoma according to TNM staging criteria/AJCC version 7 determined by PET/MRI/CT scan ECOG score 0 or 1 Life expectancy ≥6 months Candidate for surgical resection with viable melanoma tissue to ascertain ≥ 7 grams of viable cancer tissue (in aggregate), which is equivalent to a ≥ 2 cm lesion on CT/MRI or clinical examination Adequate cardiac function (≤ NYHA class II) Adequate bone marrow function, including: absolute granulocyte count (ANC) ≥ 1,500x106/L, absolute lymphocyte count (ALC) ≥ 500/mm3, platelets count ≥100,000 x 106/mm3. Adequate liver function including: serum glutamic oxaloacetic transaminases/aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the upper limit of institutional normal (IULNs), bilirubin ≤ 1.5 mg/dL or 25 µmol/L (SI units). Adequate renal function: BUN and Serum creatinine of ≤ 1.5 mg/dL or 130 µmol/L (SI units) Female subjects of childbearing potential and fertile males must agree to use adequate contraception during the course of the study. Adequate contraception includes condoms with contraceptive foam; oral, implantable or injectable contraceptives; contraceptive patch; intrauterine device; diaphragm with spermicidal gel; or a sexual partner who is surgically sterilized or postmenopausal. Post-surgery Inclusion Criteria (must be completed within 4 weeks of surgery) Histologically and clinically confirmed Stage III and/or Stage IV malignant melanoma according to TNM Staging Criteria/AJCC version 7 confirmed by PET/CT scan Measurable disease for target lesion clinical and radiological monitoring ECOG score 0 or 1 Adequate cardiac function (≤ NYHA class II) Adequate bone marrow function, liver, and renal function ≥ 6 doses of vaccine for clinical use Exclusion Criteria: Pre-Surgery Exclusion Criteria: Primary mucosal or primary ocular melanomas Other malignancies treated within the last five years, except in situ cervix carcinoma or non-melanoma skin cancer Primary or secondary immunodeficiency (including immunosuppressive disease, or systemic use of corticosteroids or other immunosuppressive medications) Patients with history of HIV1 and 2, HTLV-1, HBV or active HCV. Patients with history of connective tissue disorders Prior ipilimumab or melanoma vaccine therapy Prior therapy with IL-2 Prior chemotherapy, small molecule targeted therapy, interferon within 3 months prior to enrollment Prior investigational products administration within 4 weeks prior to enrollment Prior splenectomy Symptomatic CNS metastases or spinal cord compression Uncontrolled infection or other serious medical illnesses Any medical conditions that, in the opinion of the investigator, would preclude use of ipilimumab, including ipilimumab hypersensitivity Women who are pregnant or breast-feeding Concurrent participation in investigational trials Post-surgery Exclusion Criteria (must be completed within 4 weeks of surgery): Emergence of contraindicated clinical condition

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rabih Said, MD, MPH

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

UTHealth Memorial Hermann Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Pilot Study to Evaluate the Effects of a Vaccine (HSPPC-96) Combined With Ipilimumab in Patients With Advanced Melanoma

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