Chemotherapy + Stem Cell Transplant for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Kenneth H Yu, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: General Oncology, Inc.

Must not be taking: Immunosuppressants, CYP2b6 inducers, Disulfiram

Disqualifiers: Cholangitis, Hypertension, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of a new treatment combination for individuals with advanced pancreatic cancer who have specific genetic mutations. The treatment includes chemotherapy drugs, a stem cell transplant using autologous hematopoietic stem cells, vitamins, and ethanol. It targets those with stage IV pancreatic cancer who have BRCA1, BRCA2, or PALB2 mutations. Individuals whose pancreatic cancer has not responded well to previous treatments and who have one of these genetic changes might be suitable for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have chemotherapy within 2 weeks of enrollment, and certain medications like CYP2b6 inducers and disulfiram must be stopped 21 and 30 days before treatment, respectively.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

A previous study found that combining melphalan and BCNU (carmustine) with vitamins B12b and C, and stem cell infusion, was safe and effective for treating advanced pancreatic cancer with certain gene mutations. Research has shown that using a person's own stem cells for infusion is generally safe and well-tolerated.

Melphalan may cause more side effects than some other treatments, but it remains safe for clinical use. BCNU has been linked to liver and lung issues, though serious problems are rare.

Overall, these treatments have been used in other studies and have demonstrated manageable safety profiles. This trial will further investigate how well participants tolerate this specific combination. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the chemotherapy and stem cell transplant treatment for pancreatic cancer because it combines traditional chemotherapy with a cutting-edge approach using autologous hematopoietic stem cells. This method aims to enhance recovery by replenishing the patient's blood-forming cells after intensive chemotherapy, potentially improving outcomes and reducing recovery times. Unlike standard treatments, this approach also includes the use of vitamins B12B and C, which may offer additional support to the body's natural healing processes. This combination of treatments is designed to target the cancer more effectively while supporting the patient's overall health.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Research has shown that using a person's own stem cells can help the body fight cancer by strengthening the immune system. This approach appears promising for treating solid tumors, such as pancreatic cancer, by working with the body's natural defenses. In this trial, participants will receive a combination of treatments. Studies on BCNU, a type of chemotherapy included in this trial, have indicated its effectiveness against pancreatic tumors, especially when combined with other drugs. Melphalan, another chemotherapy drug tested in this trial, showed positive results in previous trials with patients who have BRCA-mutated pancreatic cancer. When used together, these treatments have demonstrated encouraging early results, suggesting they might improve outcomes for patients facing this challenging disease. ^{3 4 6 7 8}

Who Is on the Research Team?

Arnold Glazier, M.D.

Principal Investigator

General Oncology, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with stage IV breast or pancreatic cancer who have a BRCA1, BRCA2, or PALB2 mutation. They should not have had chemotherapy in the last 2 weeks and must be expected to live at least another 6 months. Participants need a Karnofsky score of at least 60%, indicating they can care for themselves. Smokers must quit for the trial duration, and all participants agree to use contraception.

Inclusion Criteria

Agreement to contraception for female participants of childbearing potential

Your disease can be measured or seen on medical tests using specific guidelines.

My life expectancy is mainly affected by my cancer, not other diseases.

Exclusion Criteria

I had chemotherapy for a different cancer within the last year, with a high risk of it coming back.

I have a serious heart or blood vessel condition.

Abnormal test results from lab tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stem Cell Mobilization and Collection

Granulocyte colony-stimulating factor and Plerixafor are used to mobilize bone marrow stem cells, which are collected by apheresis.

1-2 weeks

1 visit (in-person)

Treatment Cycle 1

Participants receive the first cycle of investigational drug therapy with stem cell infusion, including melphalan, BCNU, vitamin B12b, vitamin C, and ethanol.

1 week

Daily visits during treatment week

Inter-cycle Interval

Interval between the first and second treatment cycles.

6 weeks

Treatment Cycle 2

Participants receive the second cycle of investigational drug therapy with stem cell infusion.

1 week

Daily visits during treatment week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for adverse events and progression-free survival.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Hematopoietic Stem Cells
• BCNU
• Ethanol
• Melphalan
• Vitamin B12B
• Vitamin C

Trial Overview The SHARON trial tests a treatment combining chemotherapy drugs (melphalan, BCNU), vitamins (B12b, C), ethanol, and patients' own stem cells on metastatic cancer with specific genetic mutations. It's in phase 1 where safety is checked using increasing doses of vitamin C alongside other treatments given intravenously over two cycles.

How Is the Trial Designed?

Group I: Chemotherapy/stem cell treatment Experimental Treatment 6 Interventions

Autologous Hematopoietic Stem Cells is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Autologous Hematopoietic Stem Cells for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Autoimmune Diseases

Approved in European Union as Autologous Hematopoietic Stem Cells for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Autoimmune Diseases

Approved in Canada as Autologous Hematopoietic Stem Cells for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Autoimmune Diseases

Approved in Japan as Autologous Hematopoietic Stem Cells for:

• Multiple Myeloma
• Non-Hodgkin Lymphoma
• Leukemia
• Lymphoma
• Autoimmune Diseases

Who Is Running the Clinical Trial?

General Oncology, Inc.

Lead Sponsor

Trials

1

Recruited

10+

Myriad Genetics, Inc.

Industry Sponsor

Trials

18

Recruited

5,700+

Published Research Related to This Trial

High-dose cisplatin or carboplatin combined with etoposide has shown significant antitumor activity in treating various solid tumors, including nonseminomatous germ cell tumors, neuroblastoma, ovarian cancer, and brain tumors.

The study suggests that early application of these high-dose chemotherapy strategies could be crucial in preventing drug resistance, particularly in specific patient subgroups that respond well to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous bone marrow transplantation in solid tumors. Spitzer, G., Velasquez, W., Dunphy, FR., et al.[2019]

Infusing autologous non-cryopreserved bone marrow after melphalan treatment significantly accelerates bone marrow recovery, particularly improving the recovery of peripheral blood granulocytes, as observed in a study of 20 patients with malignant melanoma.

While the treatment showed some responses in melanoma patients, including complete responses in 2 cases, the overall survival benefit was limited (4-11 months), suggesting that further exploration is warranted, especially for neuroblastoma, where some patients achieved disease-free status for up to 16 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose melphalan and non-cryopreserved autologous bone marrow treatment of malignant melanoma and neuroblastoma. McElwain, TJ., Hedley, DW., Gordon, MY., et al.[2013]

In a study involving 33 patients with refractory malignancies, high-dose melphalan followed by autologous bone marrow reinfusion showed a 30% complete remission rate and a 21% partial remission rate, indicating its potential efficacy in treating difficult cancers.

The maximum tolerated dose of melphalan was determined to be 180 mg/m2, as higher doses led to significant gastrointestinal toxicity and severe infections, highlighting the need for careful dose management in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer. Lazarus, HM., Herzig, RH., Graham-Pole, J., et al.[2017]

In a study using a murine model, it was found that exposure of donor bone marrow to cytotoxic agents like busulfan significantly impaired the long-term ability of the marrow to support blood cell production in recipients, leading to decreased blood counts and survival rates.

Conversely, donor marrow exposed to cytosine arabinoside, which spares primitive stem cells, showed the least negative impact, highlighting the importance of preserving primitive stem cell content for effective hematopoiesis after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents. Neben, S., Hellman, S., Montgomery, M., et al.[2013]

Autologous stem cell transplantation (ASCT) is an effective method to reduce hematological toxicity caused by high-dose chemotherapy, allowing for more aggressive treatment of tumors.

Using peripheral blood stem cells for ASCT is particularly beneficial for patients with low bone marrow cell counts due to prior radiation or cancer, enhancing recovery after intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Peripheral stem cells: from biology to therapy]. Coppetelli, U., Tribalto, M., Papa, G.[2007]

In a phase 2 trial involving 74 patients with relapsed or refractory myeloma, the combination of gemcitabine, busulfan, and melphalan resulted in a higher rate of stringent complete remission (24.6%) compared to a control group receiving standard melphalan (12.6%), indicating improved efficacy of the new regimen.

Patients treated with the gemcitabine, busulfan, and melphalan combination also experienced significantly longer progression-free survival (15.1 months) and overall survival (37.5 months) compared to the control group, suggesting that this regimen is not only effective but also comparatively safe, despite some serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose gemcitabine, busulfan, and melphalan for autologous stem-cell transplant in patients with relapsed or refractory myeloma: a phase 2 trial and matched-pair comparison with melphalan. Nieto, Y., Valdez, BC., Pingali, SR., et al.[2022]

In a phase II study involving 15 patients with advanced colorectal adenocarcinoma, intravenous melphalan at doses not requiring bone marrow transplantation showed no objective responses, indicating limited efficacy for this treatment approach.

While the treatment caused reversible side effects like granulocytopenia and thrombocytopenia, there were no treatment-related deaths, suggesting that melphalan is safe at the administered doses, but its effectiveness in this context is questionable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of intravenous melphalan in advanced colorectal carcinoma. Moore, DF., Pazdur, R., Abbruzzese, JL.[2019]

In a study of 13 patients with advanced malignant melanoma, 24% achieved complete remission and 38% achieved partial remission after high-dose chemotherapy combined with autologous bone marrow transplantation, indicating potential efficacy of this treatment approach.

Severe side effects from nitrogen mustard limited its use, while the study highlighted the need for further investigation into prophylactic brain irradiation due to deaths from intracerebral metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation. Preliminary results--Phase I study. Thomas, MR., Robinson, WA., Glode, LM., et al.[2019]

High-dose melphalan combined with autologous bone marrow rescue has shown effectiveness in treating chemo-resistant tumors, with 5 out of 10 evaluable patients achieving partial or complete remission.

However, the treatment carries significant risks, as 3 out of 13 patients experienced melphalan-related toxicity, indicating it is best suited for younger patients with less extensive prior treatment and earlier-stage disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose melphalan with autologous marrow rescue in cancer treatment. Dewar, JM., Forgeson, GV., Dady, PJ.[2013]

In a study involving 16 patients, a high-dose chemotherapy regimen combining carboplatin and cyclophosphamide showed significant efficacy in treating germ cell cancer, with the addition of peripheral stem cell reinfusions reducing the duration of bone marrow suppression.

The treatment was generally well-tolerated, with mild non-hematological toxicities and no toxic deaths reported, suggesting that this regimen could be safe for further exploration in double or triple transplantation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa. Rodenhuis, S., Baars, JW., Schornagel, JH., et al.[2020]

Amifostine treatment allows for higher doses of chemotherapy, such as melphalan, to be safely administered alongside autologous stem cell transplantation, potentially improving treatment outcomes for patients with refractory malignancies.

In a study involving patients receiving high-dose chemotherapy, amifostine significantly reduced complications like neutropenic fever and severe stomatitis/diarrhea, indicating its effectiveness in protecting against chemotherapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of amifostine in high-dose chemotherapy and autologous hematopoietic stem cell transplantation. Phillips, GL.[2013]

In a study of 346 lymphoma patients, those aged 70 and older experienced significantly higher rates of severe cardiovascular and skin toxicities from high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT) compared to younger patients aged 60 to 69.

Despite the effectiveness of the BEAM regimen followed by AHCT, older patients had a higher risk of nonrelapse mortality and progression or death, highlighting the need for strategies to reduce toxicities in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. Dahi, PB., Lee, J., Devlin, SM., et al.[2021]

A Phase I/II trial involving 60 patients with various hematologic malignancies tested a treatment regimen combining carboplatin, etoposide, cyclophosphamide, and total body irradiation, showing promising responses, particularly in patients with high-risk acute myelocytic leukemia (AML).

While the regimen caused significant mucositis requiring pain management in 97% of patients, it was generally well tolerated, with a treatment-related mortality of 6.7%, and 7 out of 12 patients with advanced AML remaining disease-free beyond 5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An expanded phase I/II trial of cyclophosphamide, etoposide, and carboplatin plus total body irradiation with autologous marrow or stem cell support for patients with hematologic malignancies. Shea, TC., Bruner, R., Wiley, JM., et al.[2019]

In a study of 8 patients with advanced malignant melanoma, high-dose chemotherapy with melphalan and BCNU resulted in a high response rate, with 3 patients achieving a complete response and 1 a partial response.

Despite the initial responses, long-term disease-free survival was not observed, and major side effects included severe nausea/vomiting and mild mucositis, highlighting the need for careful management of treatment-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose chemotherapy with autologous bone marrow support in advanced malignant melanoma. Koeppler, H., Pflueger, KH., Seitz, R., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4922853/

Concise Review: Pancreatic Cancer and Bone Marrow- ... This work reviews advances in the current understanding of the biochemical and molecular mechanisms responsible for bone marrow-derived stem cell mobilization

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8832159/

Understanding pancreatic cancer stem cells and their role ... The purpose of this review article is to describe the pathogenesis of pancreatic cancer and to better understand the role of abnormal stem ...

3. cell.com cell.com/heliyon/fulltext/S2405-8440(24)15333-9

Advances in hematopoietic stem cell transplantation for ... This suggests that HSCT can suppress autoimmunity, including that of the pancreas, reverse the immune-mediated destruction of pancreatic β-cells ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1083879115019126

Long-Term Follow-Up of Allogeneic Hematopoietic Stem ... We wanted to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) may result in long-term survival in patients with solid cancer.

5. provider.healthybluela.com provider.healthybluela.com/medpolicies/abcbs/active/mp_pw_a070096.html

TRANS.00034 Hematopoietic Stem Cell Transplantation for ... Efficacy and safety of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus: a randomized placebo-controlled study ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024153339

Advances in hematopoietic stem cell transplantation for ... HSCT stands out as a groundbreaking therapy for autoimmune diseases, offering the potential for long-term, drug-free remission by targeting the immune system ...

7. ajmcrr.com ajmcrr.com/index.php/pub/article/view/178

Clinical safety and therapeutic efficacy of autologous bone ... Research suggests that the autologous infusion of bone marrow stem cells is safe and effective, offering the potential to be widely used in patients with ...

8. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/206540

Autologous Nonmyeloablative Hematopoietic Stem Cell ... Previous animal and clinical studies suggest that moderate immunosuppression in newly diagnosed type 1 DM can prevent further loss of insulin production and ...