SWOG clinical trial number
S1609

DART: Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors

Open
Phase
II
Accrual
77%
Abbreviated Title
DART
Status Notes
Patients may now be registered directly to S1609 without having to be enrolled on EAY131 ("NCI-MATCH"). See Revision #3 for details.



Currently OPEN Cohorts:
11, 12, 14, 15, 16, 17, 18, 19, 21, 25, 29, 36

PERMANENTLY Closed Cohorts:
1, 2, 3, 5, 7, 9, 10, 13, 20, 22, 23, 28, 31, 32, 34, 37

TEMPORARILY Closed Cohorts:
4, 6, 8, 24, 25, 26, 27, 30, 33, 35



Activation - Effective 1/13/2017, 2pm CT
Activated
01/13/2017
Participants
ALL NATIONAL CLINICAL TRIALS NETWORK MEMBERS LISTED ON TITLE PAGE

Research committees

Early Therapeutics
Breast Cancer
Gastrointestinal Cancer
Genitourinary Cancer
Lung Cancer
Melanoma

Treatment

Ipilimumab Nivolumab

Eligibility Criteria Expand/Collapse

The following histologic subtypes are NOT eligible for S1609/ DART (Appendix 18.2 of the protocol):

* Anal Cancer
* Lymphoma
* Merkel Cell Carcinoma
* Pleural Mesothelioma
* Sarcoma (bone & soft)
* Thymic carcinoma
* Uterine Leiomyosarcoma

ELIGIBILITY CRITERIA:

* Patient must meet one of the following two criteria:

1. Patient must be able to submit specimens, as indicated in Section 5.4a. NOTE: Upon IRB approval of S1609 Revision #3, patients are NOT required to participate in EAY131 (�NCI-MATCH�).

OR

2. Patient must have enrolled on EAY131 (�NCI-MATCH�) prior to EAY131 Addendum #10. They must have not had a match to a molecularly-guided therapy on EAY131, or they must be off protocol treatment on EAY131 and have no further molecularly-matched treatment recommendations per EAY131, or they must have been otherwise unable to receive EAY131 treatment.

* Patient must meet one of the following two criteria:

1. Patients must have progressed following at least one line of standard systemic therapy and there must not be other approved/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls). Patients who cannot receive other standard therapy that has been shown to prolonged survival due to medical issues will be eligible, if other eligibility criteria are met.

OR

2. Patients must have disease for which no standard treatment exists that has been shown to prolong overall survival.

In addition, patient must meet all of the following criteria:

* Patient must have histologically confirmed rare cancer identified in Section 18.1 of the protocol.

* Patients who do not qualify for one of the histologic cohorts in Section 18.1 (and are not on the ineligible histology list above) may be considered for registration in the �Not Otherwise Categorized� Rare Tumors cohort with confirmation of at least one of the study chairs via email to F1609FP/ng/fjbt/qbg/bet. See Section 18.3 Study Chair Approval Process for the Not Otherwise Categorized (NOC) Cohort.

* Patients who are determined to have a rare cancer with unknown primary site are eligible under Cohort #32 (Tumor of unknown primary (Cancer of Unknown Primary; CuP), provided that there is histologic documentation of metastatic malignancy with no discernible primary site identified from histopathologic review, physical exam and associated crosssectional imaging of the chest,abdomen, and pelvis.

* Patients enrolled directly to S1609 (without prior enrollment to EAY131) must have tissue available for pathology review. In addition, patients must be willing to submit specimens as outlined in Section 15.1.

* Patients must have a diagnostic quality CT scan or MRI, performed within 28 days prior to registration, which demonstrates measurable disease, as defined in Section 10.1 of the protocol (RECIST v. 1.1).

* No other prior malignancy is allowed except for the following:
� Adequately managed Stage I or II cancer from which the patient is currently in complete remission.
� Any other cancer from which the patient has been disease free for one year.
� Adequately managed Stage I or II follicular thyroid or prostate cancer is also eligible, wherein patient is not required to be in complete remission.

* Patients may have received either prior anti-CTLA4 or other prior anti-PD-1/anti-PD-L1 therapy, not both, provided that it is completed >/= 4 weeks prior to registration.

* Patients who had prior Grade 3 or higher immune-related adverse event (e.g., pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.) are not eligible.

* Patients with clinically controlled thyroiditis or pituitary disorders on stable replacement therapy are eligible.

* Patients are not eligible if they have had or are planned for solid organ transplant.
Patients who have received allogeneic hematopoietic stem cell transplant are eligible if:
1. The transplant occurred at least 90 days prior to registration,
2. Patient has no prior acute graft versus host disease (GVHD), and
3. Within 48 hours of registration, patient demonstrates at least 90% engraftment, defined as: ANC ≥ 500 mcl, measured over 3 consecutive days or 1 day with an ANC ≥ 1,000 mcl, or platelets ≥ 50,000 mcl measured, wherein the patient did not receive any platelet transfusions within 7 days prior to laboratory assessment.

* Patients with autoimmune disease who are otherwise eligible under protocol criterion 5.3l must not have received steroid and immunosuppressive therapy within 28 days prior to registration.

* Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >/= 28 days prior to registration and have stable disease at time of registration. Metastatic brain parenchymal disease must have been treated and patient must be off steroids for 7 days prior to registration. Patients must have a CT or MRI scan of the brain to evaluate for CNS disease within 42 days prior to registration.

* Patients must not currently be receiving any other investigational agents or any other systemic anti-cancer therapy (including radiation, excluding RANKL inhibitors and bisphosphonates). In event patient recently received any other systemic anti-cancer therapy, patient must be off therapy at least 7 days prior to registration and any therapy-induced toxicity must have recovered to </= Grade 1, except alopecia and </= Grade 2 neuropathy.

* Patients must not have prior history of allergy or known hypersensitivity to nivolumab or ipilimumab.

* Patients must be >/= 18 years of age.

* Patients must have a Zubrod Performance Status of 0-2.

* Patients must have adequate hematologic, hepatic, renal, and thyroid, and adrenal axis function as evidenced by values indicated within Section 5 of the protocol.

* Females of child bearing potential must not be pregnant or nursing and both women and men with reproductive potential must agree to contraceptive methods for duration of treatment and 23 or 31 weeks subsequent completion of treatment, respectively.

* Patients must not have known active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection at time of registration. Patients with previously treated HBV or HCV that have an undetectable viral load and no residual hepatic impairment are eligible.

* Patients who are known to be HIV-positive at registration are eligible at the time of registration:
1. CD4+ cell count greater or equal to 250 cells/mm3.
2. If patient is on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment. Once daily combinations that use pharmacologic boosters may not be used.
3. No history of non-malignancy AIDS-defining conditions other than historical low CD4+ cell counts.

* Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents,immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10 mg or equivalent). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include but are not limited to autoimmune hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), as well as symptomatic disease (e.g.: rheumatoid arthritis,systemic progressive sclerosis scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis, multiple sclerosis or glomerulonephritis). Vitiligo, alopecia, hypothyroidism on stable doses of thyroid replacement therapy, psoriasis not requiring systemic therapy within the past 3 years is permitted. Short-term steroid premedication for contrast allergy is permitted.

* Patients must not have any uncontrolled intercurrent illness including (not limited to): Symptomatic CHF (NYHA III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, Unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE v4 Grade >/= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>/= Grade 3).

* Patients must have amylase or lipase within </= 1.5 x IULN without symptoms of pancreatitis at registration, within 28 days prior to registration.

* Patients must not have symptomatic interstitial lung disease or pneumonitis.

* Patients must have fully recovered from any adverse effects of major surgery (to </=
Grade 1) at least 14 days prior to registration.

Publication Information Expand/Collapse

2016

Rare cancer research in the National Clinical Trials Network:The SWOG Experience

A Schott European Society for Medical Oncology (October 7-11, 2016, Copenhagen, Denmark), invited oral presentation

Reports & Approvals

Trial Locations

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Research Committee(s)
Breast Cancer
Activated
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Closed
07/18/1979
Accrual
100%
Closed
Phase
III
Published
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SWOG-7827

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Research Committee(s)
Breast Cancer
Activated
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Closed
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Accrual
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Phase
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Published