Olaparib + Temozolomide for Neuroendocrine Cancer

Not currently recruiting at 183 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Temozolomide, Dacarbazine, PARP inhibitors

Disqualifiers: Pregnancy, Uncontrolled cardiac conditions, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 39-52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding olaparib to the usual treatment with temozolomide can better manage neuroendocrine cancers like pheochromocytoma or paraganglioma, especially when the cancer has spread or cannot be surgically removed. Olaparib, a PARP inhibitor, stops cancer cells from repairing themselves, potentially slowing or halting their growth. The trial compares patients receiving both olaparib and temozolomide to those receiving only temozolomide. It may suit individuals with advanced pheochromocytoma or paraganglioma that has recently worsened. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong or moderate CYP3A4 inducers or inhibitors at least 21 days before joining. If you're on enzalutamide or phenobarbital, you need to stop them 5 weeks before. The protocol doesn't specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using olaparib with temozolomide is generally safe, based on previous studies. No new safety issues have emerged when these drugs are combined. Some patients have experienced stomach-related side effects, but these are usually manageable. This drug combination has been tested in other types of cancer, and results suggest it can help control the disease temporarily. Overall, evidence indicates that adding olaparib to temozolomide does not significantly increase safety risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of olaparib and temozolomide for neuroendocrine cancer because it offers a unique approach compared to standard treatments like surgery, radiation, and chemotherapy. Olaparib is a PARP inhibitor, which means it targets and blocks a protein that cancer cells need to repair their DNA, potentially making them more vulnerable to damage and death. When combined with temozolomide, a chemotherapy drug that damages DNA, this treatment could enhance the cancer-killing effect. This dual action could lead to more effective outcomes and a new option for patients who might not respond well to existing therapies.

What evidence suggests that the combination of olaparib and temozolomide could be effective for neuroendocrine cancer?

This trial will compare the combination of olaparib and temozolomide with temozolomide alone for treating neuroendocrine cancer. Research has shown that using olaparib with temozolomide may help treat certain cancers. In earlier studies, this combination reduced tumor size in nearly half of the patients. On average, patients lived 4.2 months without their cancer worsening. Olaparib stops cancer cells from repairing themselves, while temozolomide prevents them from growing and spreading. This combination might shrink or stabilize neuroendocrine cancer more effectively than temozolomide alone. ^{1 3 4 5 6}

Who Is on the Research Team?

Jaydira Del Rivero

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

Adults with advanced neuroendocrine cancer (pheochromocytoma or paraganglioma) that's spread or can't be surgically removed. Must not have had certain prior treatments, no known allergies to PARP inhibitors, and must agree to contraception. Pregnant/nursing women are excluded.

Inclusion Criteria

My bilirubin levels are normal, except for high levels due to Gilbert's syndrome.

I have never had myelodysplastic syndrome or acute myeloid leukemia.

If you have HIV, your CD4 count must be higher than 250 cells/uL and your HIV viral load must be undetectable within the past 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive temozolomide and olaparib or temozolomide alone, with cycles repeating every 21 or 28 days for up to 13 cycles

39-52 weeks

Regular visits for CT/MRI and blood sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 8 weeks until disease progression, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Olaparib
• Temozolomide

Trial Overview The trial is testing if adding Olaparib, a drug that prevents tumor cells from repairing DNA damage, to the usual chemotherapy Temozolomide helps more in treating advanced neuroendocrine cancers than chemotherapy alone.

How Is the Trial Designed?

Group I: Arm I (temozolomide, olaparib) Experimental Treatment 6 Interventions

Patients receive temozolomide PO QD and olaparib PO BID on days 1-7. Treatment with temozolomide repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Cycles of olaparib repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.

Group II: Arm II (temozolomide) Active Control 5 Interventions

Patients receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with contrast or MRI throughout the study and undergo mandatory collection of blood samples prior to treatment. Patients may optionally undergo collection of blood samples at the time of progression.

Olaparib is already approved in European Union, United States for the following indications:

Approved in European Union as Lynparza for:

• Breast cancer
• Ovarian cancer
• Fallopian tube cancer
• Peritoneal cancer
• Pancreatic cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Lynparza for:

• Ovarian, fallopian tube, and primary peritoneal cancer
• Breast cancer
• Prostate cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Olaparib (Lynparza) is approved for treating adult patients with high-risk early breast cancer that has a germline BRCA mutation, following chemotherapy treatment.

This approval highlights Olaparib's role as an adjuvant therapy, which means it is used after initial treatments to help prevent cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Treatment for High-Risk Early Breast Cancer. Aschenbrenner, DS.[2022]

In a study of 65 patients with grade 1/2 neuroendocrine tumors, capecitabine and temozolomide chemotherapy resulted in a response rate of 47.7%, with a median progression-free survival of 16.1 months and overall survival of 38.3 months.

The treatment was generally well-tolerated, with only 13.8% of patients experiencing severe toxicities, indicating that this chemotherapy combination is a promising option for managing both pancreatic and non-pancreatic neuroendocrine tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and temozolomide in grade 1/2 neuroendocrine tumors: a Spanish multicenter experience. Crespo, G., Jiménez-Fonseca, P., Custodio, A., et al.[2018]

In a retrospective study of 7 patients with metastatic pancreatic neuroendocrine tumors (pNETs) who had previously failed other treatments, the combination of capecitabine and temozolomide (CAPTEM regimen) resulted in a 43% response rate and 71% clinical benefit, indicating its potential efficacy.

The CAPTEM regimen was well-tolerated, with manageable side effects; the most severe toxicities were grade 3 thrombocytopenia and fatigue, suggesting that this treatment could be a viable option for patients with resistant pNETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of capecitabine/temozolomide (CAPTEM) regimen in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs) after failing previous therapy. Saif, MW., Kaley, K., Brennan, M., et al.[2022]

In a study of 36 patients with advanced neuroendocrine tumors treated with temozolomide, the median time to progression was 7 months, indicating a moderate efficacy of the treatment.

Temozolomide was associated with acceptable toxicity, primarily hematologic, with 14% of patients experiencing severe thrombocytopenia, while 14% showed a radiologic response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Ekeblad, S., Sundin, A., Janson, ET., et al.[2022]

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

Olaparib effectively penetrated recurrent glioblastoma tumors in patients, with measurable concentrations found in all tumor core and margin specimens, indicating its potential for therapeutic use.

The combination of olaparib with low-dose temozolomide (TMZ) was associated with increased hematological toxicity, leading to the need for intermittent dosing, but showed promising efficacy with 36% of patients remaining progression-free at 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial. Hanna, C., Kurian, KM., Williams, K., et al.[2022]

In a study of 30 patients with metastatic pancreatic endocrine carcinomas, the combination of capecitabine and temozolomide resulted in a remarkable 70% objective response rate and a median progression-free survival of 18 months.

The treatment showed a high two-year survival rate of 92% with only 12% of patients experiencing severe adverse events, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Strosberg, JR., Fine, RL., Choi, J., et al.[2022]

In a study of 20 patients with various types of glioma, the combination of olaparib and temozolomide (TMZ) showed a 50% objective radiographic response rate in patients with recurrent IDH-mutant grade 2-3 gliomas, indicating potential efficacy for this specific group.

While the treatment was generally manageable, common side effects included fatigue and gastrointestinal issues, with 30% of patients requiring dose adjustments due to toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Olaparib and Temozolomide for the Treatment of Glioma: A Retrospective Case Series. Schaff, LR., Kushnirsky, M., Lin, AL., et al.[2023]

In a study of 67 patients with low-grade pituitary tumors, the combination of temozolomide (TMZ) and radiotherapy showed a significantly higher total effective rate (91.89%) compared to radiotherapy alone (70.00%).

The combined treatment resulted in greater reductions in serum levels of prolactin, insulin-like growth factor-1, and growth hormone, indicating enhanced efficacy in managing hormone levels associated with pituitary tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Trail Investigating Temozolomide Neoadjuvant Chemotherapy Combined with Radiotherapy in Low-Grade Pituitary Tumors. Cui, J., Shen, J., Ru, X., et al.[2022]

Citations

1. onclive.com onclive.com/view/olaparib-temozolomide-fails-to-meet-pfs-end-point-in-previously-treated-advanced-uterine-leiomyosarcoma

Olaparib/Temozolomide Fails to Meet PFS End Point in ... Olaparib plus temozolomide was not superior to pazopanib or trabectedin for the treatment of patients with advanced uterine leiomyosarcoma.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7319046/

Combination Olaparib and Temozolomide in Relapsed ... The confirmed overall response rate (ORR) was 41.7% (20/48 evaluable); median progression free survival (mPFS) was 4.2 months (95% CI 2.8–5.7); ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04394858

Study Details | NCT04394858 | Testing the Addition of an ... This phase II trial studies how well the addition of olaparib to the usual treatment, temozolomide, works in treating patients with neuroendocrine cancer ...

4. cancernetwork.com cancernetwork.com/view/olaparib-combo-provides-meaningful-benefit-in-uterine-leiomyosarcoma

Olaparib Combo Provides Meaningful Benefit in Uterine ... Olaparib plus temozolomide produced a median progression-free survival (PFS) of 6.9 months (95% CI, 5.4-NE). The PFS rate was 65% at 6 months, ...

5. oncnursingnews.com oncnursingnews.com/view/olaparib-plus-temozolomide-induces-promising-response-duration-in-uterine-leiomyosarcoma

Olaparib Plus Temozolomide Induces Promising Response ... We found that the combination of olaparib with a lower [than usual] dose of chemotherapy seemed to be a very active combination in uLMS models.

6. onclive.com onclive.com/view/dr-d-amato-on-efficacy-data-with-olaparib-plus-temozolomide-in-advanced-uterine-leiomyosarcoma

Dr D'Amato on Efficacy Data With Olaparib Plus ... No new safety signals were identified with olaparib plus temozolomide, D'Amato continued Gastrointestinal toxicities were observed but remained ...