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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02452281
Recruitment Status : Withdrawn (PI departure, operational issues)
First Posted : May 22, 2015
Last Update Posted : January 25, 2016
Sponsor:
Collaborator:
Agenus Inc.
Information provided by (Responsible Party):
Rabih Said, The University of Texas Health Science Center, Houston

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: ipilimumab Drug: HSPPC-96 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma Shock
Drug Information available for: Ipilimumab

Arm Intervention/treatment
Experimental: ipilimumab + HSPPC-96
  • 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.
Drug: ipilimumab
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.
Other Name: Yervoy ®

Drug: HSPPC-96
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.
Other Name: heat shock protein-peptide complex 96; Prophage; Vitespen




Primary Outcome Measures :
  1. All enrolled patients who receive at least one dose of study drug (HSPPC-96) will be evaluated for safety. (adverse events) [ Time Frame: 2 years ]
    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.

  2. • To assess immunological response by surrogate markers of immune response and modulation of tumor cellular microenvironment [ Time Frame: 2 years ]
    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 :
  1. Objective Response Rate (ORR) [ 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 ]
    ORR defined by complete and partial responses.

  2. Progression Free Survival (PFS) [ 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 ]
    Time to recurrence is time from surgery until recurrence or last tumor evaluation without recurrence.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02452281


Locations
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United States, Texas
UTHealth Memorial Hermann Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Rabih Said
Agenus Inc.
Investigators
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Principal Investigator: Rabih Said, MD, MPH The University of Texas Health Science Center, Houston
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Responsible Party: Rabih Said, Assistant Professor, Department of Internal Medicine, Division of Oncology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02452281    
Other Study ID Numbers: C-100-41
HSC-MS-14-0070 ( Other Identifier: UTHSC-H CPHS (IRB) )
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: January 25, 2016
Last Verified: January 2016
Keywords provided by Rabih Said, The University of Texas Health Science Center, Houston:
Therapeutically Unresectable
Stage III or Stage IV
Malignant Melanoma
Advanced Melanoma
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents