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Cervical CancerPhase 1/2CervISANCT02128126

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

A Phase 1/2 study testing ISA101/ISA101b in people with Cervical Cancer, run by ISA Pharmaceuticals at 15 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Cervical Cancer
What is being tested?
ISA101/ISA101b
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
15 sitesin 3 countries
Study dates
Sep 2013to Aug 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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:
  • Clinical suspicion or radiological evidence of brain or leptomeningeal metastases.
  • Previous or current malignancies at other sites, with the exception of basal or squamous cell carcinoma of the skin and with the exception of other malignancies from which the patient may be considered cured as evidenced by complete regression of all lesions >10 years ago.
  • Active HIV, chronic hepatitis B or C infection.
  • Patients of childbearing potential not willing to consistently and correctly us a contraceptive method according to ICH (M3) resulting in low failure rate, i.e. less that 1% per year such as oral contraceptives or use of effective means of contraception.
  • Pregnancy or lactation. Serum pregnancy test to be performed within 7 days prior to study treatment start in patients of childbearing potential.
  • Major surgical procedure within 28 days prior to the first study treatment.
  • Uncontrolled sustained hypertension (systolic > 180 mm Hg and/or diastolic > 110mm Hg).
  • Clinically significant (i.e. active) cardiovascular disease defined as:
  • Stroke within ≤ 6 months prior to day 1;
  • Transient Ischemic Attack (TIA) within ≤ 6 months prior to day 1;
  • Myocardial infarction within ≤ 6 months prior to day 1;
  • Unstable angina;
  • New York Heart Association (NYHA) Grade II or greater Congestive Heart Failure (CHF);
  • Serious cardiac arrhythmia requiring medication;
  • History of severe bronchial asthma and/or severe allergy.
  • Evidence of any other medical conditions that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.

Trial locations and contacts

15 sites in 3 countries.

15 sites in 3 countries

Netherlands6 sites

  • NKI/AVL

    Amsterdam, 1066 CX

  • AMC

    Amsterdam, 1105 AZ

  • UMCG

    Groningen, 9713 GZ

  • LUMC

    Leiden, 2333 ZA

  • MUMC

    Maastricht, 6229 HX

  • Radboud UMC

    Nijmegen, 6525 GA

Other trials in Netherlands

Belgium5 sites

  • UZA

    Antwerp, 2650

  • Chirec Cancer Institute

    Brussels, 1180

  • UZG

    Ghent, B-9000

  • UZL

    Leuven, 3000

  • CHU of Liege Site Citadelle

    Liège, B-4000

Other trials in Belgium

Germany4 sites

  • Universitätsklinikum Düsseldorf - Frauenklinik

    Düsseldorf, 40225

  • Universitätsklinikum Essen - Klinik für Frauenheilkunde

    Essen, 45147

  • Medizinische Hochschule Hannover - Klinik für Frauenheilkunde

    Hanover, 30625

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

Other trials in Germany

About this study

Official title: A Multicenter, Open Label Phase I/II Study to Determine the Safety and Immune Modulating Effects of the Therapeutic Human Papilloma Virus 16 (HPV16) E6/E7 Long Peptides Vaccine (ISA101/ISA101b) Immunotherapy in Combination With Standard of Care Therapy (Carboplatin and Paclitaxel With or Without Bevacizumab) in Women With HPV16 Positive Advanced or Recurrent Cervical Cancer Who Have no Curative Treatment Options

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.

Read the detailed description

A majority of cervical carcinomas are caused by an uncontrolled, persistent infection with high risk Human Papilloma Virus (HPV). ISA101/ISA101b is a novel therapeutic synthetic long peptide (SLP) vaccine targeting HPV16 which is being developed and has shown efficacy in patients with high-grade premalignant vulvar lesions caused by HPV with only minor toxicity. For most advanced cancers, chemotherapy remains the treatment modality of choice but has been considered to be immunosuppressive. However, accumulating evidence indicates that many modalities of conventional chemotherapy not only are less immunosuppressive than previously thought but in fact can exert favorable effects on the tumor micro-environment by interfering with suppressive immune cells and by stimulating the release of immune activating molecules by tumor cells. Thus chemotherapy may enhance tumor-specific immunity and synergize with cancer immunotherapy. Addition of pegylated interferon alpha (IFNα) two-b (IIb) to vaccination might even further improve the immune response. This multicenter, open label, non-randomized Phase I/II study will be performed to assess the safety and tolerability of the ISA101/ISA101b vaccine, and the immune modulating effects of ISA101 (with or without pegylated IFNα)/ISA101b when combined with carboplatin and paclitaxel, with or without bevacizumab.

Conditions
Cervical Cancer
Being tested
ISA101/ISA101b
Keywords
Advanced or recurrent cervical cancer, HPV16 positive, No curative treatment options
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ISA101/ISA101bDrug

    Also called HPV Type 16 E6/E7 Synthetic Long Peptides Vaccine

    Four dose levels ISA101/ISA101b

Study groups in NCT02128126
Study groupRoleWhat they receive
ISA101/ISA101bExperimentalThe 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.
Receives: Drug: ISA101/ISA101b

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 4 months

Secondary outcomes (1)

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

    Measured: one year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2014 (estimated)
  2. Study startSep 2013
  3. Primary completionAug 2018
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02128126
Sponsor's protocol ID
ISA-HPV-01-12
Other IDs
2013-001804-12
Acronym
CervISA
Status last verified
Mar 2019
First submitted
18 Apr 2014
Last updated
6 Mar 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31060612

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ISA101/ISA101b in people with Cervical Cancer, run by ISA Pharmaceuticals at 15 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Netherlands, Belgium, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HPV-specific immune responses (time frame: 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02128126, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.

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