Cancer of Unknown Primary SitePhase 2CheCUPNCT04131621
Nivolumab/Ipilimumab in Second Line CUP-syndrome
A Phase 2 study testing Nivolumab/Ipilimumab in people with Cancer of Unknown Primary Site, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
To compare the efficacy of nivolumab plus ipilimumab in subjects with high vs. Intermediate/low TMB poor-prognosis CUP (non-specific subset) who are relapsed or refractory to platinum-based first-line chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Unknown Primary Site
- What is being tested?
- Nivolumab/Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 194 participants
- Where
- 1 siteGermany
- Study dates
- 12 Dec 2019to Dec 2022
- Phase
- Phase 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form
- Able and willing to comply with the study protocol
- Age ≥ 18 years at time of signing Informed Consent Form
- Histologically-confirmed disseminated or advanced unresectable CUP diagnosed according the criteria defined in the 2015 ESMO Clinical Practice Guidelines for CUP. Acceptable disease histology includes:
- Adenocarcinoma of unknown primary site (ACUP)
- Poorly differentiated adenocarcinoma of unknown primary site
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- Poorly differentiated carcinoma of unknown primary site
- Squamous cell carcinoma of unknown primary site (SCUP)
- At least one lesion that is measurable according to RECIST v1.1
- Availability of a tumor FFPE block either fresh or archival if obtained ≤ 6 months at Screening that is sufficient for generation of a TruSight Oncology 500 (TSO500) panel at the central reference pathology laboratory
- Availability of test reports confirming local CUP diagnosis. If test reports confirming local CUP diagnosis are not available, an FFPE block must be submitted that is sufficient to allow for central confirmation of CUP diagnosis
- Disease relapse or progression after at least three cycles of a platinum-based standard chemotherapy. There is no upper limit of prior treatments received.
- ECOG performance status of 0 - 2
- Life expectancy ≥ 12 weeks
- Eligible for immune checkpoint inhibitor
- Adequate hematologic and end-organ function
- For women of childbearing potential and men capable of reproduction: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 5 months for women and 7 months for men, respectively after the last dose of study treatment.
- Recovery from significant toxicity from platinum-doublet therapy to Grade ≤ 1, except for alopecia and for neurosensory toxicity, which must be ≤ 2
- Recovery from active infections requiring intravenous antibiotics, with antibiotic therapy ceased for ≥ 7 days prior to planned start of therapy
Who cannot join
- Subjects with any of the specific non-CUP neoplasms identified in the ESMO CUP guidelines, including:
- Non-epithelial cancer
- Extragonadal germ-cell tumor
- Subjects belonging to any of the following subsets of CUP with favorable prognoses:
- Poorly differentiated carcinoma with midline distribution
- Women with papillary adenocarcinoma of the peritoneal cavity
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- Women with adenocarcinoma involving only the axillary lymph nodes
- Squamous cell carcinoma restricted to cervical lymph nodes
- Poorly and well differentiated neuroendocrine tumors
- Men with blastic bone metastases and elevated PSA
- Subjects with a single, small tumor potentially resectable and/or amenable to radiotherapy with curative intent
- Colon cancer-type CUP
- Known presence of brain or spinal cord metastasis (including metastases that have been irradiated), as determined by CT or magnetic resonance imaging (MRI) evaluation during screening
- History or known presence of leptomeningeal disease
- Uncontrolled or symptomatic hypercalcemia (serum calcium ≥ 2.9mmol/L)
- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
- Known human immunodeficiency virus (HIV) infection
- Positive for hepatitis C virus (HCV) infection at screening
- Positive for hepatitis B surface antigen (HBsAg) at screening
- Active tuberculosis at Screening
- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia (including active ventricular arrhythmia requiring medication), or unstable angina
- Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
- History of malignancy other than CUP within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
- Prior allogeneic stem cell or solid organ transplantation
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Known allergy or hypersensitivity to any component of the immunotherapy, including history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins and to Chinese hamster ovary cell products or other recombinant human or humanized antibodies for nivolumab and ipilimumab.
- Subjects with an active, known or suspected autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, myocarditis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents, or other immuno-suppressive medications within 14 days of study treatment. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents for adults, or > 0.25 mg/kg daily prednisone equivalent for adolescents are permitted, in the absence of active autoimmune disease.
- Subjects who received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 5) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
- Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment (subjects with prior cytotoxic or investigational products < 4 weeks prior to treatment initiation might be eligible after discussion between investigator and sponsor, if toxicities from the prior treatment have been resolved to Grade 1 (NCI CTCAE version 5).
- Subjects must not have received a live / attenuated vaccine within 30 days of first treatment.
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment or intention of fathering a child within 7 months after the last dose of study treatment.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University of Heidelberg
Heidelberg
Alwin Kraemer
About this study
Official title: A Phase II, Open-label, Non-randomized, Multi-center Study Evaluating the Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Cancer of Unknown Primary Site Who Are Relapsed After or Refractory to Platinum-based Chemotherapy
To compare the efficacy of nivolumab plus ipilimumab in subjects with high vs. Intermediate/low TMB poor-prognosis CUP (non-specific subset) who are relapsed or refractory to platinum-based first-line chemotherapy.
To evaluate the efficacy of nivolumab plus ipilimumab in subjects with poor-prognosis CUP (non-specific subset) who are relapsed or refractory to platinum-based first-line chemotherapy
- Conditions
- Cancer of Unknown Primary Site
- Being tested
- Nivolumab/Ipilimumab
- Medical subject headings
- Neoplasms, Unknown Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab/IpilimumabBiological
Immune checkpoint inhibitor combination
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab/Ipilimumab | Experimental | Not described Receives: Biological: Nivolumab/Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Months
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start12 Dec 2019
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
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 Cancer of Unknown Primary SiteStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 194 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alwin Kraemer, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131621
- Sponsor's protocol ID
- CA209-8WY
- Acronym
- CheCUP
- Status last verified
- Apr 2020
- First submitted
- 16 Oct 2019
- Last updated
- 15 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Pouyiourou M, Kraft BN, Wohlfromm T, Stahl M, Kubuschok B, Loffler H, Hacker UT, Hubner G, Weiss L, Bitzer M, Ernst T, Schutt P, Hielscher T, Delorme S, Kirchner M, Kazdal D, Ball M, Kluck K, Stenzinger A, Bochtler T, Kramer A. Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial. Nat Commun. 2023 Oct 24;14(1):6761. doi: 10.1038/s41467-023-42400-5.
PubMed 37875494
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label, Non-randomized, Multi-center Study Evaluating the Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Cancer of Unknown Primary Site Who Are Relapsed After or Refractory to Platinum-based Chemotherapy
- ClinicalTrials.gov ID
- NCT04131621
- Acronym / sponsor ID
- CheCUP / CA209-8WY
- Conditions
- Cancer of Unknown Primary Site
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 194 participants (estimated)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- 12 Dec 2019 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 18 Oct 2019 (actual)
- 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.
To compare the efficacy of nivolumab plus ipilimumab in subjects with high vs. Intermediate/low TMB poor-prognosis CUP (non-specific subset) who are relapsed or refractory to platinum-based first-line chemotherapy.
To evaluate the efficacy of nivolumab plus ipilimumab in subjects with poor-prognosis CUP (non-specific subset) who are relapsed or refractory to platinum-based first-line chemotherapy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab/Ipilimumab | Experimental | Biological: Nivolumab/Ipilimumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed Informed Consent Form
- Able and willing to comply with the study protocol
- Age ≥ 18 years at time of signing Informed Consent Form
- Histologically-confirmed disseminated or advanced unresectable CUP diagnosed according the criteria defined in the 2015 ESMO Clinical Practice Guidelines for CUP. Acceptable disease histology includes:
- At least one lesion that is measurable according to RECIST v1.1
Key exclusion criteria (34 listed)
- Subjects with any of the specific non-CUP neoplasms identified in the ESMO CUP guidelines, including:
- Subjects belonging to any of the following subsets of CUP with favorable prognoses:
- Known presence of brain or spinal cord metastasis (including metastases that have been irradiated), as determined by CT or magnetic resonance imaging (MRI) evaluation during screening
- History or known presence of leptomeningeal disease
- Uncontrolled or symptomatic hypercalcemia (serum calcium ≥ 2.9mmol/L)
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 |
|---|---|---|
| Nivolumab/IpilimumabImmune checkpoint inhibitor combination | Biological | Nivolumab/Ipilimumab |
Primary outcome
Progression-free survival
Time frame: 3 months
Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2020.
- Derived from this study: PubMed 37875494Pouyiourou M, Kraft BN, Wohlfromm T, Stahl M, Kubuschok B, Loffler H, Hacker UT, Hubner G, Weiss L, Bitzer M, Ernst T, Schutt P, Hielscher T, Delorme S, Kirchner M, Kazdal D, Ball M, Kluck K, Stenzinger A, Bochtler T, Kramer A. Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial. Nat Commun. 2023 Oct 24;14(1):6761. doi: 10.1038/s41467-023-42400-5.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab/Ipilimumab in people with Cancer of Unknown Primary Site, run by University Hospital Heidelberg at 1 site in Germany.
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 19 inclusion and 34 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: status not confirmed, as of the sponsor's last update on 15 Apr 2020. 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 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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alwin Kraemer (0049622142 ext. 1440, a.kraemer@dkfz.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 3 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 NCT04131621, 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 15 Apr 2020.