Evaluation of a Multi-phosphopeptide Vaccine Plus PolyICLC in Participants With High Risk and Advanced Malignancies

NCT01846143 | Completed Phase 1 DMC

• 1 other identifier: 15832
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn what effects (good and bad) experimental phosphopeptide vaccines plus a tetanus peptide and other substances called polyICLC and Montanide ISA-51 have on people with melanoma. The investigators will also look at whether the experimental reagents cause any changes in the immune system.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Safety

  Adverse events occurring in each subject will be reported until 30 days post administration of the last vaccine.

  30 days post administration of the last vaccine

Secondary Outcomes (1)

• Immunogenicity of phosphopeptide vaccines

  Through Day 85

Study Arms (3)

Arm A: pBCAR3-phosphopeptide + tet vaccine plus polyICLC

EXPERIMENTAL

pBCAR3-phosphopeptide + tet vaccine plus polyICLC The vaccines will be administered in two treatment cycles. During cycle one, three vaccines will be administered over a 3-week period on days 1, 8, and 15. During cycle two, three vaccines will be administered over a 9-week period on days 36, 57, 78. Participants will be vaccinated with 100 mcg each of the phosphopeptides and 200 mcg of the tetanus peptide (Peptide-tet). The peptides will be administered subcutaneously (0.5 ml) and intradermally (0.5 ml) in Montanide ISA-51 VG adjuvant at six separate vaccine sites in a minimum of two separate extremities. Poly ICLC: PolyICLC will be administered by a separate 0.5 ml injection (0.25 ml subcutaneously and 0.25 ml intradermally), immediately after, and directly into the precise site where the peptide emulsion was given. We will administer 1 mg per vaccine.

Biological: pBCAR3-phosphopeptide

Arm B: pIRS2-phosphopeptide + tet vaccine plus polyICLC

EXPERIMENTAL

The vaccines will be administered in two treatment cycles. During cycle one, three vaccines will be administered over a 3-week period on days 1, 8, and 15. During cycle two, three vaccines will be administered over a 9-week period on days 36, 57, 78. Participants will be vaccinated with 100 mcg each of the phosphopeptides and 200 mcg of the tetanus peptide (Peptide-tet). The peptides will be administered subcutaneously (0.5 ml) and intradermally (0.5 ml) in Montanide ISA-51 VG adjuvant at six separate vaccine sites in a minimum of two separate extremities. Poly ICLC: PolyICLC will be administered by a separate 0.5 ml injection (0.25 ml subcutaneously and 0.25 ml intradermally), immediately after, and directly into the precise site where the peptide emulsion was given. We will administer 1 mg per vaccine.

Biological: pIRS2-phosphopeptide

Arm C: 2-MpP+ tet vaccine plus polyICLC

EXPERIMENTAL

The vaccines will be administered in two treatment cycles. During cycle one, three vaccines will be administered over a 3-week period on days 1, 8, and 15. During cycle two, three vaccines will be administered over a 9-week period on days 36, 57, 78. Participants will be vaccinated with 100 mcg each of the phosphopeptides and 200 mcg of the tetanus peptide (Peptide-tet). The peptides will be administered subcutaneously (0.5 ml) and intradermally (0.5 ml) in Montanide ISA-51 VG adjuvant at six separate vaccine sites in a minimum of two separate extremities. Poly ICLC: PolyICLC will be administered by a separate 0.5 ml injection (0.25 ml subcutaneously and 0.25 ml intradermally), immediately after, and directly into the precise site where the peptide emulsion was given. We will administer 1 mg per vaccine.

Biological: 2-MpP (pBCAR3-phosphopeptide + pIRS2-phosphopeptide)

Interventions

pBCAR3-phosphopeptide BIOLOGICAL

Also known as: tet vaccine, polyICLC

Arm A: pBCAR3-phosphopeptide + tet vaccine plus polyICLC

pIRS2-phosphopeptide BIOLOGICAL

Arm B: pIRS2-phosphopeptide + tet vaccine plus polyICLC

2-MpP (pBCAR3-phosphopeptide + pIRS2-phosphopeptide) BIOLOGICAL

Arm C: 2-MpP+ tet vaccine plus polyICLC

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven high-risk or advanced solid malignancies including melanoma, colorectal cancer, ovarian cancer, breast cancer, or non small-cell lung cancer (NSCLC) that meets one of the following criteria:
• Melanoma:
• For Arms A and B: Stage IIIB-IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission For Arm C: Stage IIA-IV melanoma rendered clinically free of disease by surgery, other therapy, or spontaneous remission For all Arms: Stage III or IV melanoma with disease, for patients who have failed other approved therapies, are not candidates for approved therapies, or refuse other approved therapies.
• Staging will be based on the 7th edition AJCC staging system for melanoma and other cancers. Staging of mucosal melanomas will be based on the following system modified from the cutaneous melanoma staging system: IIA: 2.01- 4mm primary, or stage IIB: \> 4mm primary, lymph node metastases = stage III, distant metastases = stage IV.
• Breast cancer:
• Metastatic stage IV or unresectable breast cancer on endocrine therapy or on no other systemic therapy who have had at least one prior therapy for their metastatic disease. Patients who are metastatic, but with no measurable disease are eligible. Participation in this study should not preclude the delivery of any approved and appropriate anti-cancer therapies, but they are not to be delivered concurrent with this trial, except that patients may participate while taking endocrine-only therapy (eg: aromatase inhibitors or tamoxifen or Lupron). Patients may also participate during pre-planned chemotherapy holidays.
• Patients after resection for stage IIIA to IV breast cancer (any ER, PR, or Her2 status) after surgery, radiation therapy, adjuvant chemotherapy, or HER2 targeted therapy.
• For Arm C only: Stage I-II, high risk patients with either triple negative breast cancer or HER2 positive disease are also eligible if the tumor is larger than 1 cm. Vaccine will be offered after surgery, radiation therapy or adjuvant chemotherapy (if indicated)
• Colorectal cancer:
• Metastatic (advanced) colorectal cancer that has failed at least 2 prior chemotherapy regimens, including 5-FU, ironotecan, and oxaliplatin.
• High-risk resected metastatic colorectal cancer after resection of liver metastases and after approved agents are administered. For patients after surgical resection of liver metastases,
• Eligibility to Arms A and B will be limited to those with at least 3 of the following risk factors: node-positive primary, disease-free interval less than 1 year, more than 1 liver metastasis, size of largest liver metastasis greater than 5 cm, and serum CEA greater than 200 ng/ml.
• Eligibility to Arm C will be limited to those with at least 1 of the 5 risk factors listed above.
• Ovarian cancer:
• Ovarian or fallopian tube cancer that is recurrent or treatment refractory with no remaining alternative, approved therapy options with a reasonable possibility of clinical response.

You may not qualify if:

• Patients who are currently receiving systemic cytotoxic chemotherapy, radiation, or other experimental therapy, or who have received this therapy within the preceding 4 weeks. Gamma knife or stereotactic radiosurgery may be administered within the prior 4 weeks, but must not be administered less than one week prior to study enrollment. Patients who are currently receiving nitrosoureas or who have received this therapy within the preceding 6 weeks.
• Patients will not be eligible if there is clinically detectable malignancy deemed likely by the investigator to require intervention during the first 12 weeks of the study that would require premature discontinuation. Examples for such circumstances may include untreated bone metastases at risk for fracture, and rapidly progressive low volume disease.
• Patients with known or suspected allergies to any component of the vaccine.
• Patients receiving the following medications at study entry or within the preceding 4 weeks are excluded:
• Agents with putative immunomodulating activity (with the exception of non-steroidal anti-inflammatory agents and topical steroids (see section 4.2.5(3)).
• Allergy desensitization injections.
• Systemic corticosteroids, administered parenterally or orally inhaled steroids (e.g. Advair®, Flovent®, Azmacort®) are not permitted. Topical corticosteroids are acceptable, including steroids with very low solubility administered nasally for local effects only (e.g. Nasonex®).
• Any pharmacologic growth factors (e.g. GM-CSF, G-CSF, erythropoietin).
• Interferon therapy
• Interleukin-2 or other interleukins.
• Toll-like receptor agonists, including imiquimod, resiquimod, or polyICLC.
• Participants may not have been vaccinated previously with any of the synthetic phosphopeptides included in this protocol.
• Pregnancy or the possibility of becoming pregnant during vaccine administration. Female patients of child-bearing potential must have a negative pregnancy test (urinary or serum beta-HCG) prior to administration of the first vaccine dose. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. The methods are specified in the consent form and include the following: Norplant, IUD, Dep-Provera, Birth Control Pills, Birth Control Patch, and Sterilization. The following may be used if combined with other birth control methods: Condoms, Jellies or foam, Diaphragm, Rhythm, Withdrawal, Sponge, or Cervical cap.
• Women must also not be breast feeding.
• Patients in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol, in the opinion of the investigator.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Engelhard VH, Obeng RC, Cummings KL, Petroni GR, Ambakhutwala AL, Chianese-Bullock KA, Smith KT, Lulu A, Varhegyi N, Smolkin ME, Myers P, Mahoney KE, Shabanowitz J, Buettner N, Hall EH, Haden K, Cobbold M, Hunt DF, Weiss G, Gaughan E, Slingluff CL Jr. MHC-restricted phosphopeptide antigens: preclinical validation and first-in-humans clinical trial in participants with high-risk melanoma. J Immunother Cancer. 2020 May;8(1):e000262. doi: 10.1136/jitc-2019-000262.

  PMID: 32385144 DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Victor Engelhard, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

• Craig L. Slingluff, Jr., MD

  University of Virginia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: April 30, 2013
• First Posted: May 3, 2013
• Study Start: May 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: November 1, 2015
• Last Updated: August 12, 2016

Record last verified: 2016-08

Locations

US (1)