Recurrent Ovarian CancerPhase 1/2PITCHNCT01637532
Feasibility of the Combination of Chemotherapy (Carbo/Caelyx or Carbo/Doxorubicin) With Tocilizumab (mAb IL-6R) and Peg-Intron in Patients With Recurrent Ovarian Cancer
A Phase 1/2 study testing tocilizumab and interferon alpha 2-b and Carboplatin and Caelyx or doxorubicin in people with Recurrent Ovarian Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this interventional study is to determine the feasibility to combine standard chemotherapy (Carbo/Caelyx or doxorubicin) for recurrent ovarian cancer with immunotherapy (Tocilizumab and Peg-Intron). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Ovarian Cancer
- What is being tested?
- tocilizumab and interferon alpha 2-b and Carboplatin and Caelyx or doxorubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2011to Sep 2013
- 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
- Histologically proven epithelial ovarian cancer
- Progression of disease or relapse after previous therapy with platinum
- Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper normal limit (UNL) within 3 months and confirmed
- Age ≥18 years
- WHO performance status 0-2
- Adequate bone marrow function: WBC ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
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- Adequate liver function: bilirubin ≤1.5 x UNL range, ALAT and/or ASAT
- 2.5 x UNL (<5x UNL in case of liver metastases), Alkaline Phosphatase ≤5 x UNL
- Adequate renal function: the calculated creatinine clearance should be
- 50 mL/min
- Survival expectation > 3 months
- Patients must be accessible for treatment and follow-up
- Written informed consent according to the local Ethics Committee requirements
Who cannot join
- Chemotherapy within past 3 months
- Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
- Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
- Known hypersensitivity reaction to any of the components of the treatment
- Pregnancy or lactating
- Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
- Infection with tuberculosis and hepatitis B or C
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Chemo-Immunotherapy: Observational Trial of Carboplatin-pegylated Liposomal Doxorubicin (PLD) or Doxorubicin Combination Chemotherapy With Tocilizumab, a Humanized Monoclonal Antibody Against the Human Interleukin-6 (IL-6) Receptor, and Pegylated Interferon Alpha (Peg-Intron) for Patients With Recurrent Ovarian Cancer.
The purpose of this interventional study is to determine the feasibility to combine standard chemotherapy (Carbo/Caelyx or doxorubicin) for recurrent ovarian cancer with immunotherapy (Tocilizumab and Peg-Intron).
This study combines standard chemotherapy Carboplatin-Caelyx or doxorubicin with a monoclonal antibody against IL-6R (tocilizumab). High IL-6 levels correlate with poor prognosis and chemoresistance in ovarian cancer patients. In cases of chemoresistant ovarian cancer, therefore, modulation of the IL-6 pathway, by blocking the IL-6 receptor, may represent a promising strategy to both abolish drug resistance and amplify host immunity in patients with recurrent ovarian cancer. Blockade of the IL-6/IL-6R pathway may enhance immunogenic cell death and restore local normal DC maturation. In addition, the use of interferon-alpha (Peg-Intron) allows the full maturation of DC, thereby enhancing the anti-tumor response.
- Conditions
- Recurrent Ovarian Cancer
- Being tested
- tocilizumab and interferon alpha 2-b, Carboplatin and Caelyx or doxorubicin
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tocilizumab and interferon alpha 2-bDrug
During first three chemotherapy cycles, tocilizumab and/or Peg-Intron are added.
Tocilizumab is given in a dose-escalation scheme (1,2,4,8mg/kg n=3) and Peg-Intron is adminstered subcutaneously 1.0ug/kg
Carboplatin and Caelyx or doxorubicinDrug
Standard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Other | Carboplatin/Caelyx Receives: Drug: Carboplatin and Caelyx or doxorubicin |
| Group 2 | Experimental | Carboplatin/Caelyx or doxorubicin plus Tocilizumab Receives: Drug: tocilizumab and interferon alpha 2-b; Drug: Carboplatin and Caelyx or doxorubicin |
| Group 3 | Experimental | Carboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron Receives: Drug: tocilizumab and interferon alpha 2-b; Drug: Carboplatin and Caelyx or doxorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron
The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .
Measured: two years
Secondary outcomes (2)
The effect of chemo-immunotherapy on the immune system
Study the effect of chemo-immunotherapy on the immune system by assessing changes in plasma signature (eg IL6, IL8, VEGF, CRP) dendritic cell phenotype and T- and B-cell responses to known tumor antigens in ovarian cancer (eg NY-ESO, p53), antibodies to antigens associated with immunogenic cell death (CRT, HMGB1) and in tumor tissue by gene array
Measured: two years
The relation between anti-tumor immunity and clinical outcome
Study the relation between anti-tumor immunity and clinical outcome (response (RECIST 1.1), progression free survival (PFS) and overall survival(OS))
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2012 (estimated)
- Study startFeb 2011
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen
- Responsible party
- Principal investigator, J.R. Kroep, Leiden University Medical Center
- Investigators
- G Blecourt, Study director, LUMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01637532
- Sponsor's protocol ID
- PITCH trial
- Acronym
- PITCH
- Status last verified
- Jan 2016
- First submitted
- 15 Apr 2012
- Last updated
- 26 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dijkgraaf EM, Santegoets SJ, Reyners AK, Goedemans R, Wouters MC, Kenter GG, van Erkel AR, van Poelgeest MI, Nijman HW, van der Hoeven JJ, Welters MJ, van der Burg SH, Kroep JR. A phase I trial combining carboplatin/doxorubicin with tocilizumab, an anti-IL-6R monoclonal antibody, and interferon-alpha2b in patients with recurrent epithelial ovarian cancer. Ann Oncol. 2015 Oct;26(10):2141-9. doi: 10.1093/annonc/mdv309. Epub 2015 Jul 27.
PubMed 26216383
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chemo-Immunotherapy: Observational Trial of Carboplatin-pegylated Liposomal Doxorubicin (PLD) or Doxorubicin Combination Chemotherapy With Tocilizumab, a Humanized Monoclonal Antibody Against the Human Interleukin-6 (IL-6) Receptor, and Pegylated Interferon Alpha (Peg-Intron) for Patients With Recurrent Ovarian Cancer.
- ClinicalTrials.gov ID
- NCT01637532
- Acronym / sponsor ID
- PITCH / PITCH trial
- Conditions
- Recurrent Ovarian Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- University Medical Center Groningen
- Study start
- Feb 2011
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 11 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this interventional study is to determine the feasibility to combine standard chemotherapy (Carbo/Caelyx or doxorubicin) for recurrent ovarian cancer with immunotherapy (Tocilizumab and Peg-Intron).
This study combines standard chemotherapy Carboplatin-Caelyx or doxorubicin with a monoclonal antibody against IL-6R (tocilizumab). High IL-6 levels correlate with poor prognosis and chemoresistance in ovarian cancer patients. In cases of chemoresistant ovarian cancer, therefore, modulation of the IL-6 pathway, by blocking the IL-6 receptor, may represent a promising strategy to both abolish drug resistance and amplify host immunity in patients with recurrent ovarian cancer. Blockade of the IL-6/IL-6R pathway may enhance immunogenic cell death and restore local normal DC maturation. In addition, the use of interferon-alpha (Peg-Intron) allows the full maturation of DC, thereby enhancing the anti-tumor response.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Other | Drug: Carboplatin and Caelyx or doxorubicinCarboplatin/Caelyx |
| Group 2 | Experimental | Drug: tocilizumab and interferon alpha 2-b, Drug: Carboplatin and Caelyx or doxorubicinCarboplatin/Caelyx or doxorubicin plus Tocilizumab |
| Group 3 | Experimental | Drug: tocilizumab and interferon alpha 2-b, Drug: Carboplatin and Caelyx or doxorubicinCarboplatin/Caelyx or doxorubicin plus Tocilizumab plus Peg-Intron |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically proven epithelial ovarian cancer
- Progression of disease or relapse after previous therapy with platinum
- Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper normal limit (UNL) within 3 months and confirmed
- Age ≥18 years
- WHO performance status 0-2
Key exclusion criteria (7 listed)
- Chemotherapy within past 3 months
- Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
- Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
- Known hypersensitivity reaction to any of the components of the treatment
- Pregnancy or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tocilizumab and interferon alpha 2-bDuring first three chemotherapy cycles, tocilizumab and/or Peg-Intron are added. Tocilizumab is given in a dose-escalation scheme (1,2,4,8mg/kg n=3) and Peg-Intron is adminstered subcutaneously 1.0ug/kg | Drug | Group 2, Group 3 |
| Carboplatin and Caelyx or doxorubicinStandard chemotherapeutic care given in every arm as standard care. A total of 6 cycles is the aim. | Drug | Group 1, Group 2, Group 3 |
Primary outcome
The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron
Time frame: two years
The safety (NCI-CTCv4.0)and efficacy (immune-monitoring)of the new combination will be measured .
2 secondary outcomes
The effect of chemo-immunotherapy on the immune system
Time frame: two years
The relation between anti-tumor immunity and clinical outcome
Time frame: two years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2016.
- Derived from this study: PubMed 26216383Dijkgraaf EM, Santegoets SJ, Reyners AK, Goedemans R, Wouters MC, Kenter GG, van Erkel AR, van Poelgeest MI, Nijman HW, van der Hoeven JJ, Welters MJ, van der Burg SH, Kroep JR. A phase I trial combining carboplatin/doxorubicin with tocilizumab, an anti-IL-6R monoclonal antibody, and interferon-alpha2b in patients with recurrent epithelial ovarian cancer. Ann Oncol. 2015 Oct;26(10):2141-9. doi: 10.1093/annonc/mdv309. Epub 2015 Jul 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
G Blecourt study director
LUMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing tocilizumab and interferon alpha 2-b and Carboplatin and Caelyx or doxorubicin in people with Recurrent Ovarian Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
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 13 inclusion and 7 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 26 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
The feasibility (NCI-CTCv4.0) to combine carboplatin and PLD or doxorubicin with tocilizumab as well as with tocilizumab and Peg-Intron (time frame: two years). 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 NCT01637532, 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 26 Jan 2016.