Study of the Therapeutic Vaccine (ISA101/ISA101b) to Treat Advanced or Recurrent Cervical Cancer

NCT02128126 | Completed Phase 1 DMC

• 2 other identifiers: ISA-HPV-01-122013-001804-12
• Study Type: interventional
• Target: 93
• Locations: 3 countries
• Sites: 15

Brief Summary

The purpose of the study is to assess the safety, tolerability and the HPV-specific immune responses of different doses of ISA101 vaccine with or without pegylated IFNα as combination therapy with carboplatin and paclitaxel. To qualitatively assess the safety profile and the HPV-specific immune responses of ISA101b vaccine compared to ISA101 at the same dose levels. To assess the safety and the HPV-specific immune responses of ISA101b vaccine with carboplatin, paclitaxel with or without bevacizumab.

Conditions

Cervical Cancer

Keywords

Advanced or recurrent cervical cancer; HPV16 positive; No curative treatment options

Outcome Measures

Primary Outcomes (1)

• HPV-specific immune responses

  HPV-specific immune responses to different doses of the ISA101 vaccine with or without pegylated interferon alpha (INFα) as combination therapy with carboplatin and paclitaxel will be determined. The HPV-specific immune responses to ISA101b will be qualitatively compared to the responses at the same dose level(s) of ISA101.

  4 months

Secondary Outcomes (1)

• Evaluate the clinical efficacy by antitumor efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  one year

Other Outcomes (1)

• Evaluate the general responsiveness of the immune system as measured by explorative assays.

  4 months

Study Arms (1)

ISA101/ISA101b

EXPERIMENTAL

The maximum total treatment duration for a patient is six cycles (1 cycle is 21 days) for a total of 18 weeks. On day 15 of cycles 2, 3 and 4 patients are to receive the vaccination scheme of ISA101/ISA101b. Patients will be vaccinated with a fixed dose of ISA101/ISA101b every three weeks for a total of three rounds of vaccination. Four dose levels of ISA101 have been tested. ISA101b will be tested in bridging cohorts.

Drug: ISA101/ISA101b

Interventions

ISA101/ISA101b DRUG

Four dose levels ISA101/ISA101b

Also known as: HPV Type 16 E6/E7 Synthetic Long Peptides Vaccine

ISA101/ISA101b

Eligibility Criteria

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

You may qualify if:

• Women ≥ 18 years of age.
• Cervical cancer confirmed by histology.
• Advanced or metastatic or recurrent cervical cancer confirmed by clinical and/or radiological proof with no curative treatment options.
• For cohort 10 (and 12), i.e. patients eligible to receive bevacizumab at each site per standard of care, patients may be primary stage IVB (including persistent) or first recurrent carcinoma of the uterine cervix (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Prior treatment with chemotherapy for recurrent disease is not permitted. However, one prior line of chemotherapy with platinum during primary radio-chemotherapy or platinum-base chemotherapy as neoadjuvant chemotherapy prior to surgery is permitted
• Tumour must be HPV16 positive.
• Patients should be eligible for chemotherapy with carboplatin and paclitaxel, and have consented with chemotherapy with carboplatin and paclitaxel, before the start of the informed consent procedure for the study.
• Performance status (WHO scale/ECOG) 1.
• Written informed consent according to local guidelines.
• Written approval by the treating physician/investigator of his/her clinical judgment that the patient has a reasonable life expectancy and is sufficiently fit and motivated to complete the study treatment and comply to all study procedures conform the protocol.

You may not qualify if:

• Treatment:
• Prior treatment with anti-HPV agents.
• Chronic systemic steroid use. Local application (i.e. stable doses of topical or inhaled corticosteroids) is allowed.
• Less than 4 weeks since the last treatment with other cancer therapies, (i.e. endocrine therapy, immunotherapy, radiotherapy, chemotherapy, etc), less than 8 weeks for cranial radiotherapy, and less than 6 weeks for nitrosoureas and mitomycin C.
• Toxicities resulting from previous anti-cancer therapy must be resolved to ≤ grade 2.
• Recent treatment (within 30 days of first study treatment) with another investigational drug.
• Patients with known hypersensitivity to any component of the Investigational Medicinal Product.
• Any contraindication to the use of authorized applied products (i.e. paclitaxel, carboplatin or bevacizumab).
• Haematology and biochemistry:
• Inadequate bone marrow function: Absolute Neutrophil Count (ANC) \< 1.5 x 109/L, or platelet count \< 100 x 109/L or hemoglobin \< 6 mmol/L.
• Inadequate liver function, defined as:
• Serum (total) bilirubin \> 2 x upper normal limit (ULN);
• Aspartate Aminotransferase (ASAT) or Alanine Aminotransferase (ALAT) \> 2.5 x ULN (\> 5 x ULN in patients with liver metastases);
• Alkaline phosphatase levels \> 2.5 x ULN (\> 5 x ULN in patients with liver metastases, or \> 10 x ULN in patients with bone metastases).
• Other:

Sponsors & Collaborators

• ISA Pharmaceuticals: lead
• Dutch Cancer Society: collaborator

Study Sites (15)

UZA

Antwerp, 2650, Belgium

Location

Chirec Cancer Institute

Brussels, 1180, Belgium

Location

UZG

Ghent, B-9000, Belgium

Location

UZL

Leuven, 3000, Belgium

Location

CHU of Liege Site Citadelle

Liège, B-4000, Belgium

Location

Universitätsklinikum Düsseldorf - Frauenklinik

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen - Klinik für Frauenheilkunde

Essen, 45147, Germany

Location

Medizinische Hochschule Hannover - Klinik für Frauenheilkunde

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

NKI/AVL

Amsterdam, 1066 CX, Netherlands

Location

AMC

Amsterdam, 1105 AZ, Netherlands

Location

UMCG

Groningen, 9713 GZ, Netherlands

Location

LUMC

Leiden, 2333 ZA, Netherlands

Location

MUMC

Maastricht, 6229 HX, Netherlands

Location

Radboud UMC

Nijmegen, 6525 GA, Netherlands

Location

Related Publications (1)

• Domingos-Pereira S, Galliverti G, Hanahan D, Nardelli-Haefliger D. Carboplatin/paclitaxel, E7-vaccination and intravaginal CpG as tri-therapy towards efficient regression of genital HPV16 tumors. J Immunother Cancer. 2019 May 6;7(1):122. doi: 10.1186/s40425-019-0593-1.

  PMID: 31060612 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Winald Gerritsen, Oncologist

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2014
• First Posted: May 1, 2014
• Study Start: September 1, 2013
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: March 6, 2019

Record last verified: 2019-03

Locations

NL (6); DE (4); BE (5)