A Phase II Trial of Ipilimumab and Nivolumab for the Treatment of Rare Cancers
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|ClinicalTrials.gov Identifier: NCT02923934|
Recruitment Status : Active, not recruiting
First Posted : October 5, 2016
Last Update Posted : March 3, 2021
The three tumour streams that will be studied in this protocol are: (i) upper GI malignancies (comprising intra-hepatic/extra-hepatic cholangiocarcinomas,gall bladder cancers and duodenal cancers).); (ii) neuroendocrine tumours (inc. Pancreatic, bronchial and intestinal carcinoid tumours) and (iii) rare gynaecological tumours (including but will not be limited to: vaginal or vulval carcinomas, clear cell carcinoma of the ovary, low grade serous ovarian cancer, mixed mullarian tumours (carcinosarcoma), sarcomas of the female genital tract and granulosa cell tumours).
The role of immunotherapy is being defined in more common cancer types, however because of their rarity, the efficacy of immunotherapy for these cancers is poorly defined.
This protocol provides an important opportunity to establish whether the combination of nivolumab & ipilimumab has efficacy in these cancers.
|Condition or disease||Intervention/treatment||Phase|
|Gastrointestinal Cancer Neuroendocrine Tumours Malignant Female Reproductive System Neoplasm||Drug: Ipilimumab Drug: Nivolumab||Phase 2|
This is a phase 2 clinical trial of nivolumab combined with ipilimumab in subjects with rare cancers. This study will allow an evaluation of the clinical benefit, as measured by progression free survival (PFS) and overall survival (OS), provided by nivolumab combined with ipilimumab. If the safety profile is acceptable and clinically efficacy is seen, this study would support the use of nivolumab combined with ipilimumab in subjects with these cancers.
Study Rationale Clinically advanced rare cancers pose a significant clinical challenge because evidence based treatments are seldom available for patients suffering from these malignancies. Despite little evidence that shows clinical benefit, these patients are often treated with chemotherapeutic agents that are used in patients with more common malignancies that arise from the same anatomical site. Furthermore, because of small numbers, they are often excluded from clinical trials with newer agents. The rare care project has defined a rare malignancy as a cancer with an incidence of less than 6/100000/year. It is estimated that 42,000 people are diagnosed with a form of rare or less common cancer in Australia every year (www.canceraustralia.gov.au). The cancer specific survival of patients diagnosed with a rare malignancy is significantly lower than with common cancers highlighting the need to improve management and treatment of these patients. Given the recent success of cancer immunotherapy with checkpoint regulators such as ipilimumab and nivolumab in a whole range of different cancer types, it can be postulated that these agents could be beneficial in rare cancers and improve the overall outlook of patients with these conditions. It is proposed here that patient cohorts which fall within three distinct tumour streams will be examined, with all patients receiving ipilimumab and nivolumab as combination immunotherapy. The three tumour streams are defined as: upper GI malignancies (comprising intra-hepatic/ extra-hepatic cholangiocarcinomas,gall bladder cancers and duodenal cancers).); neuroendocrine tumours (inc. Pancreatic, bronchial and intestinal carcinoid tumours) and rare gynaecological tumours (including but will not be limited to: vaginal or vulval carcinomas, clear cell carcinoma of the ovary, low grade serous ovarian cancer, mixed mullarian tumours (carcinosarcoma), sarcomas of the female genital tract and granulosa cell tumours). Although overall response rates for individual tumour types will not be established due to sample size (target 20 patients per tumour stream, n=60 total), descriptive information of individual patient responses will guide immune-directed therapies to responsive rare tumour types and may be broadened to tumour streams.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Masking Description:||This is an open label study, all patients receive the same treatment as per the protocol.|
|Official Title:||A Phase II Clinical Trial Evaluating Ipilimumab and Nivolumab in Combination for the Treatment of Rare Gastrointestinal, Neuro-Endocrine and Gynaecological Cancers|
|Actual Study Start Date :||August 22, 2017|
|Actual Primary Completion Date :||April 27, 2020|
|Estimated Study Completion Date :||December 2023|
Experimental: Ipilimumab and Nivolumab
All Subjects will be treated with: Nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg concurrently every 3 weeks for 4 doses followed by nivolumab only at 3mg/kg every 2 weeks until progression (up to 48 total doses of nivolumab)
CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) is a key regulator of T cell activity. Ipilimumab is a CTLA-4 immune checkpoint inhibitor that blocks T-cell inhibitory signals induced by the CTLA-4 pathway, increasing the number of tumor reactive T effector cells which mobilize to mount a direct T-cell immune attack against tumor cells. CTLA-4 blockade can also reduce T regulatory cell function, which may lead to an increase in anti-tumor immune response.
Other Name: YERVOY ®
A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death-1 (PD-1,PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs (antigen presenting cells). This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity.
Other Name: Opdivo
- To determine the clinical efficacy of the combination treatment of ipilimumab with nivolumab in rare cancers. [ Time Frame: at 12 weeks following randomisation then every 6 weeks until disease progression ]Clinical benefit rate for whole population (CR (complete response)+PR (partial response)+SD (stable disease)>3 months)
- To identify whether a common predictive biomarker or immune signature can be identified in responding patients that can occur irrespective of tumour type. [ Time Frame: Pre-dose samples will be collected during the first two cycles (6 weeks/cycle) ]Pre-dose Blood and Serum samples on Day 1 week 1 and Day 1 week 4 for cycle 1 and Day 1 week 1 for cycle 2 (each cycle is 6 weeks). Optional tumour biopsies will be assessed at Day 1 week 1 and Day 1 week 4 for both cycles 1 and 2.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02923934
|Australia, New South Wales|
|Border Medical Oncology Unit|
|Albury, New South Wales, Australia, 2640|
|Sydney, New South Wales, Australia, 2145|
|Clayton, Victoria, Australia, 3168|
|Heidelberg, Victoria, Australia, 3078|
|Peter MacCallum Cancer Centre|
|Melbourne, Victoria, Australia, 3000|
|Study Chair:||Oliver Klein, MD||ONJCRI and Austin Health|
|Study Chair:||Jonathan Cebon, MD||ONJCRI and Austin Health|