** Registration to A012103- HO1 Quality of Life Sub Study is Closed to Accrual as of 07/15/2025**

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH TH Ann Arbor, Canton, Chelsea, Brighton, and Livonia, Genesys, Hurley, Lehigh Valley, Henry Ford

Eligibility Criteria:

A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

3.2.1 Age ≥ 18 years

3.2.2 ECOG Performance Status 0-2

3.2.3 Triple Negative Breast Cancer

3.2.3.1 Patients with a history of stage T1cN1-2 or T2-4N0-2 breast cancer according to the primary tumor-regional lymph node anatomic staging criteria of the American Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator in radiologic assessment, clinical assessment or both.

3.2.3.2 Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual DCIS is allowed. Isolated tumor cells are considered node negative.

3.2.3.3 ER and PR ≤10%; HER2-negative by ASCO/CAP guidelines (IHC and FISH)

3.2.3.4 If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts 

3.2.4 Prior Treatment

3.2.4.1 Patients must have received neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles. All systemic chemotherapy must have been completed preoperatively.

3.2.4.2 An interval of no more than 12 weeks between the completion date of the final surgery and the date of randomization. Note: Adjuvant radiation can be given on study. If given, it is encouraged to be given concurrently with pembrolizumab, per investigator discretion. Treatment with adjuvant pembrolizumab is strongly discouraged prior to participation in this trial, but if administered (e.g., if patients are awaiting pathology results), pembrolizumab may be administered for up to 6 weeks post-surgery and must be completed prior to registration.

3.2.4.3 Use of investigational anti-cancer agents must be discontinued at time of registration.  

3.2.4.4 Adequate excision: Surgical removal of all clinically evident disease in the breast and lymph nodes as follows:

Breast surgery: Total mastectomy or breast-conserving surgery with histologically negative margins, including no ink on tumor for DCIS, at the time of excision.

For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of ductal carcinoma in-situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates DCIS at the line of resection, additional operative procedures may be performed to obtain clear margins. If DCIS is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection. 

Lymph node surgery: 

For a patient with clinically N0 disease, a sentinel lymph node biopsy should have been performed at time of surgical evaluation, and if pathologically node positive, the patient is no longer eligible. Isolated tumor cells are considered node-negative.

For a patient with clinically N1 disease at diagnosis (with positive results from a fine-needle aspiration, core biopsy, or sentinel node biopsy performed prior to preoperative therapy) additional surgical evaluation of the axilla following preoperative therapy is required. 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

 **A012301-IM1 Closed to Accrual Effective 09/09/2025**

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health IHA (Brighton, Ann Arbor, Canton, Chelsea), Livonia, Genesys, Sparrow, Henry Ford, SJMO, St Alphonsus

Eligibility Criteria:

3.2.1 Unilateral invasive adenocarcinoma of the breast that is histologically confirmed

3.2.1.1 Invasive breast cancer is estrogen receptor positive in ≥10% of cells

3.2.1.2 HER2 negative by current ASCO/CAP guidelines

3.2.2 The patient must have a multigene assay with a low-risk score, including any of the following (if more than one genomic assay was obtained, both are required to be low-risk): 

• Oncotype DX Recurrence Score ≤ 25

• Mamma Print low risk  

• Prosigna Risk of Recurrence ≤40 

3.2.3 Surgical pathology requirements:

3.2.3.1 Tumor size must be ≤3 cm by pathologic evaluation.

3.2.3.2 Adequate surgical removal of all clinically evident disease in the breast with either breast conserving surgery or mastectomy. Negative margins on final pathology are required. Additional excisions may be performed to obtain clear margins before registration.

3.2.3.3 No clinical (cN1, cN2, cN3) or pathologic (pN1mi, pN1, pN2, or pN3) evidence of lymph node involvement on either needle biopsy or surgical lymph node assessment. Patients with pN0(i+) or pN0 (mol+) are eligible. 

o Surgical axillary staging (sentinel lymph node biopsy ± axillary lymph node dissection) is completed according to physician discretion.

o For patients with negative preoperative axillary ultrasonography, clinicians may selectively choose to forego surgical axillary staging. Ipsilateral axillary ultrasound showing no lymph node involvement with no evidence of lymphadenopathy or suspicious thickening is required in this scenario. 

3.2.4 No tumors that are considered pT4

3.2.5 No definitive clinical or radiologic evidence of metastatic disease

3.2.6 No palpable or radiographically suspicious axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histologic confirmation that these lymph nodes are negative for tumor 

3.2.7 No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast, unless biopsied and found to be benign

3.2.8 An interval of no more than 20 weeks between the date of surgery and the date of registration. 3.2.9 Must have had a bilateral mammogram or MRI within 6 months prior to registration. 

3.2.10 Must be intending to take endocrine therapy for at least 5 years duration 

3.2.11 Prior Treatment

3.2.11.1 No prior treatment with endocrine therapy or chemotherapy for the currently diagnosed breast cancer prior to registration. (Short course endocrine therapy of ≤ 6 weeks duration is acceptable after core biopsy and before surgery, if genomic testing is assessed on the biopsy core and meets eligibility requirements for a low-risk score.)

3.2.11.2 No use of oral hormone replacement therapy within 7 days prior to registration.  

3.2.12 Age ≥ 18 years and female 

3.2.13 ECOG Performance Status ≤ 2 

3.2.14 Postmenopausal status confirmed as meeting one of the following:

• No spontaneous menses ≥1 year or

• No menses for <1 year with FSH and estradiol levels within a postmenopausal range according to institutional standards or

• Previous bilateral surgical oophorectomy 

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.

CURRENT SITES CREDENTIALED: Trinity Health IHA ( Ann Arbor, Brighton, Chelsea, Canton), Livonia, Oakland, Sparrow

Eligibility Criteria:

3.2.1 Documentation of Disease

3.2.1.1 Patients (females and males) with clinical stage T1c-T3 (or Tx) and nodal stage N0-N1 (except T3N1 tumors, which are not eligible)

3.2.1.2 Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual DCIS is allowed. Patients with residual isolated tumor cells at surgery are considered node-positive and are not eligible.

3.2.1.3 HER2+ by ASCO/CAP guidelines. Central pathology review is not required. In cases where there were multiple tumor sites in breast/nodes that had HER2 testing at diagnosis, at least one site must have been HER2+ AND the treating investigator must feel it is in the patient’s best interest to be treated as having HER2+ breast cancer.

3.2.1.4 Known hormone receptor status as defined by ASCO/CAP guidelines. ER and PR of any values are allowed. Hormone receptor positive status can be determined by either known positive ER or known positive PR status; hormone receptor negative status must be determined by both known negative ER and known negative PR.

3.2.1.5 If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts (including the requirement that at least one biopsied site on each side must have been HER2+) 

3.2.2 Age ? 18 years

3.2.3 ECOG Performance Status 0-2

3.2.4 Prior Treatment

3.2.4.1 Patients must have received neoadjuvant chemotherapy in combination with trastuzumab with or without pertuzumab for a minimum of 12 weeks. All chemotherapy must have been completed preoperatively. Patient must complete a minimum of 12 weeks of coverage with trastuzumab and a maximum of 24 weeks in the combined neoadjuvant and adjuvant setting prior to trial registration. Trastuzumab may have been administered either weekly or q3weeks. (For purposes of this eligibility criterion, a single dose of q3week trastuzumab would provide 3 weeks of coverage; a single dose of q1week trastuzumab would provide 1 week of coverage. If a q3week dose of trastuzumab were administered and then the subsequent dose was delayed for any period of time, that would still count as 3 weeks of coverage.) Administration of endocrine therapy for treatment of this breast cancer is allowed prior to trial registration. If a patient received prior breast cancer endocrine therapy (eg tamoxifen or aromatase inhibitor) for DCIS or preventive indication, and endocrine therapy is indicated for treatment of their current breast cancer, then prior endocrine therapy must have been stopped >12 months prior to registration on this protocol. No use of investigational anti-cancer agents at time of registration.

3.2.4.2 Patient must register within 14 weeks of final surgery.  

**PLEASE SEE THE CURRENT VERSION OF PROTOCOL FOR FULL ELIGIBILITY LIST** 

*Credentialing required. Please check your site's credentialing status.*

**Effective 05/09/18 Patient Pre-Registration (Step 0) is Temporarily Suspended

**Effective 08/13/18 Arm 2 is closed to accrual
CURRENT SITES CREDENTIALED:
SJMH, Lehigh, Saginaw

Pre-registration eligibility:
-Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process.
-TX, T1-4N0-1orNxM0* *M1 disease includes spread to distant lymph nodes, organs, and ascites
-Local radiographic reading must be consistent with borderline resectable cancer of the pancreatic head and must meet one or more of the following on CT/MRI:
--An interface is present between the primary tumor and the superior mesenteric vein or portal vein and measures greater than or equal to 180° of the circumference of the vessel wall
--Short-segment occlusion of the SMV-PV is present with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
--Short segment interface (of any degree) is present between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction
--An interface is present between the tumor and superior mesenteric artery or celiac axis measuring 180° of the circumference of the vessel wall

Registration eligibility: 
-Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
-No prior chemotherapy or radiation for pancreatic cancer
-No previous definitive resection of pancreatic cancer
-No grade 2 or greater neuropathy
-ECOG PS 0-1

*DTL Required- Physicians must sign toxicity grid

CURRENT SITES COMPLETED:  SJMH, SJMO, Saginaw, Sparrow, Genesys Hurley, Hurley, Livonia, St. John Detroit, St. John Macomb

-Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C).
-DNA Mismatch Repair (MMR) Status: Presence of deficient (d) DNA mismatch repair (dMMR). MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR.
-Tumors must have been completely resected.
-Entire tumor must be in the colon (rectal involvement is an exclusion).
-No evidence of residual involved lymph node disease or metastatic disease at the time of registration based on clinician assessment of imaging.
-ECOG Performance Status 0- 2
-No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for colon cancer except for one cycle of mFOLFOX6. Cycle 1 of mFOLFOX6 must have been administered

-No systemic daily treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of registration.

*DTL Required- Physicians must sign toxicity grid

CURRENT SITES COMPLETED: SJMH, Genesys Hurley, Hurley, Lehigh Valley, Saginaw, St. John, Macomb

-Well- or moderately-differentiated neuroendocrine tumors of pancreatic and non-pancreatic (i.e. carcinoid) origin by local pathology.

The pathology report must state ONE of the following: 1) well- or moderately-differentiated neuroendocrine tumor, 2) low- or intermediate-grade neuroendocrine tumor, or 3) carcinoid tumor or atypical carcinoid tumor.
-Locally advanced/ unresectable or metastatic disease
-Histological documentation of neuroendocrine tumor of pancreatic, gastrointestinal (GI), lung, or unknown primary site.
-Target lesions must have shown evidence of disease progression in the 12 months prior to registration

-Patients must have measurable disease
-Patient must have failed at least one prior systemic therapy that included everolimus.
-Patients should have resolution of any toxic effects of prior therapy (except alopecia and fatigue) to grade 1 or less.
-ECOG PS must be 0-2

*DTL Required- Physicians must sign toxicity grid CREDENTIALING REQUIRED. Please check your site's credentialing status. CURRENT SITES CREDENTIALED: SJMH (AA, Brighton, Canton, Chelsea), Sparrow, SJMO, GenHur, LVHN, Livonia, Saginaw, St. John, Macomb,

Eligibility Criteria:

*DTL Required- Physicians must sign toxicity grid

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH (Ann Arbor, Brighton, Chelsea, Canton, St. Mary's Livonia, Genesys, St. John Hospital, Macomb, LVHN

Eligibility Criteria:

3.2.1 Documentation of Disease

• Histologic Documentation: Histologically-proven advanced (metastatic or unresectable primary) pheochromocytoma or paraganglioma.
• Stage: Advanced (metastatic or unresectable primary) disease
• Tumor Site: Histologically-proven pheochromocytoma or paraganglioma
• Radiographic Evaluation: Radiographic evidence of disease progression by RECIST v1.1 criteria in the 12 months prior to registration.

3.2.2 Measurable disease as defined in Section 11.0.

Lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as = 1 cm with CT or MRI (or = 1.5 cm for lymph nodes). Non-measurable disease includes disease smaller than these dimensions or lesions considered truly non-measurable including: leptomeningeal disease, ascites, pleural or pericardial effusion, lymphangitic involvement of skin or lung.

3.2.3 Prior Treatment

Prior treatment with other chemotherapy, radiotherapy (including peptide radionuclide receptor therapy [PRRT]), or surgery must be completed = 28 days prior to registration. Patients must have recovered from any effects of any major surgery prior to registration.

Prior treatment with radiolabeled MIBG must be completed = 12 weeks prior to registration and lifetime cumulative 131I-MIBG dose must be < 1000 MBq kg-1 (36 mCi kg-1).

Prior treatment with antibiotics must be completed = 7 days prior to registration.

No prior treatment with temozolomide, dacarbazine, or a poly ADP ribose polymerase (PARP) inhibitor.

No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

3.2.4 Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.

Therefore, for women of childbearing potential only, a negative pregnancy test done = 7 days prior to registration is required.

3.2.5 Contraception

Therapy utilized in this trial is associated with medium/high fetal risk.

Women of childbearing potential and their partners, who are sexually active, must agree to use two highly effective forms of contraception in combination (as listed in Appendix V). This should be started from the time of registration and continue throughout the period of taking study treatment and for at least 1 month after last dose of study drug(s), or they must totally/truly abstain from any form of sexual intercourse (see Appendix V).

Male patients must use a condom during treatment and for 3 months after the last dose of study drug(s) when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential (as listed in Appendix V). Male patients should not donate sperm throughout the period of taking study drug(s) and for 3 months following the last dose of study drug(s).

3.2.6 Age = 18 years

3.2.7 ECOG Performance Status: 0-2

3.2.8 Required Initial Laboratory Values

• Absolute Neutrophil Count = 1,500/mm3
• Platelet Count = 100,000/mm3
• Hemoglobin = 10 mg/dL*
• Total Bilirubin = 1.5 x upper limit of normal (ULN)**
• AST/ALT = 3.0 x ULN
• Creatinine < 1.5 x ULN

OR

Calc. Creatinine Clearance > 50 mL/min***

*In the absence of transfusion within the previous 24 hours.

**Except in the case of Gilbert’s syndrome, then Total Bilirubin must be = 3.0 x ULN.

***Calculated by Cockcroft-Gault equation.

3.2.9 Patient History

- No indication of uncontrolled, potentially reversible cardiac condition(s) as determined by investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 500 msec, electrolyte disturbances, etc.) and no known congenital long QT syndrome.

- No extensive bilateral lung disease or pneumonitis.

- No abnormal organ or bone marrow function = 28 days prior to registration.

- Patients with HIV positivity are allowed if CD4 Count > 250 cells/µL and they have an undetectable HIV viral load within 6 months of registration.

- No active infection.

- No history of myelodysplastic syndrome (MDS) (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukemia.

- No known gastrointestinal condition(s) that might predispose for drug intolerability or poor drug absorption.

- No known medical condition causing an inability to swallow oral formulations of agents.

- No history of allergic reaction attributed to compounds of similar chemical or biologic composition to PARP inhibitors.

3.2.10 Concomitant Medications

Concurrent use of combination antiretroviral therapy (ART) is not permitted.

Chronic concomitant treatment with strong or moderate CYP3A4 inducers or inhibitors is not allowed. Patients must discontinue the agent(s) = 21 days prior to registration; enzalutamide and/or phenobarbital must be discontinued = 5 weeks prior to registration. See Section 8.1.8 for more information.

CREDENTIALING REQUIRED. Please check your site's credentialing status.
CURRENT SITES CREDENTIALED: SJMH (AA, Brighton, Canton, Chelsea), Saginaw, St. John, LVHN

Eligibility Criteria:

Pre-Registration Eligibility Criteria (Step 0)

Documentation of Disease

Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma.

TNM Stage: Tx-4, N0-1, M0*

*M0 disease does not include spread to distant lymph nodes and organs

Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic MRI scan and 2) chest CT:

• No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
• Less than 180° interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence

• No evidence of metastatic disease

Measurable disease or non-measurable disease as defined in Section 11.0.

Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging.

Registration Eligibility Criteria (Step 1)

- A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months).

Disease Status

Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at IROC Ohio.

Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection.

- Prior Treatment

No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer.

-Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.

Therefore, for women of childbearing potential only, a negative pregnancy test done = 14 days prior to registration is required.

Age = 18 years

- ECOG Performance Status 0-1

- Total Neuropathy Score 2

- Required Initial Laboratory Values

• Absolute Neutrophil Count (ANC) = 1,500/µL
• Platelet Count = 100,000/µL
• Total Bilirubin = 1.5 x upper limit of normal (ULN)*
• Creatinine = 1.5 x ULN

OR

Calc. Creatinine Clearance = 30 mL/min**

*If obstructive jaundice is present, then biliary drainage must be initiated and Total Bilirubin = 3.0.

**Calculated using the Cockcroft-Gault equation

Comorbid Conditions

- No known Gilbert’s Syndrome or known homozygosity for UGAT1A1*28 polymorphism.

- No comorbid conditions that would prohibit curative-intent pancreatectomy.

Concomitant Medications

- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration. See Section 8.1.11 for more information.

- Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration. See Section 8.1.12 for more information.