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

Trial Summary

What is the purpose of this trial?

The clinical trial is a phase 1, single-arm trial that will evaluate the safety of the investigational treatment on metastatic cancer in patients who have a deleterious or suspected deleterious BRCA1, BRCA2, or PALB2 genetic alteration. The investigational treatment will involve 2 cycles of a combination of intravenous melphalan, BCNU, low-dose I.V. ethanol, vitamin B12b, and vitamin C in association with autologous hematopoietic stem cell infusion. A dose-escalation schedule will be employed for vitamin C.

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.

What data supports the effectiveness of the treatment involving chemotherapy and stem cell transplant for pancreatic cancer?

Research shows that high-dose melphalan, used with autologous bone marrow rescue, can be effective in treating tumors resistant to standard chemotherapy, with some patients achieving partial or complete remission. This suggests potential benefits for similar treatments in other cancers, like pancreatic cancer. ^{1 2 3 4 5}

Is the combination of chemotherapy and stem cell transplant generally safe for humans?

The combination of chemotherapy and stem cell transplant has been studied in various conditions and is generally considered safe, though it can cause significant side effects like mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract) and nausea/vomiting. Some studies report a treatment-related mortality rate of around 6.7%, and older patients may experience more severe toxicities. However, with supportive treatments like amifostine, some side effects can be managed, allowing for higher doses of chemotherapy. ^{6 7 8 9 10}

How does the treatment of chemotherapy and stem cell transplant for pancreatic cancer differ from other treatments?

This treatment combines high-dose chemotherapy with autologous stem cell transplantation, which helps reduce the severe blood-related side effects of chemotherapy by replenishing the body's blood-forming cells. This approach is particularly useful for tumors that are resistant to standard chemotherapy doses, offering a potential option for patients in the early stages of disease who have not undergone extensive prior treatments. ^{3 11 12 13 14}

Research Team

Arnold Glazier, M.D.

Principal Investigator

General Oncology, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation. Preliminary results--Phase I study. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Autologous bone marrow transplantation in solid tumors. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

High dose melphalan with autologous marrow rescue in cancer treatment. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

High dose melphalan and non-cryopreserved autologous bone marrow treatment of malignant melanoma and neuroblastoma. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer. [2017]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. [2021]

9. United States 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. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

High-dose chemotherapy with autologous bone marrow support in advanced malignant melanoma. [2018]

11. Italy pubmed.ncbi.nlm.nih.gov

[Peripheral stem cells: from biology to therapy]. [2007]

12. England pubmed.ncbi.nlm.nih.gov

Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa. [2020]

13. England 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. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of intravenous melphalan in advanced colorectal carcinoma. [2019]