Sequential Olaparib + Adavosertib for Cancer

Recruiting in Palo Alto (17 mi)

Overseen ByTimothy Yap

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Trial Summary

What is the purpose of this trial?This phase I trial studies the side effects and best dose of adavosertib when given together with olaparib in treating patients with solid tumors that have spread to other places in the body (advanced) with selected mutations. Adavosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Giving olaparib and adavosertib one after the other may shrink or stabilize advanced solid tumors as successfully as using them together, with fewer side effects.

Eligibility Criteria

This trial is for adults with advanced solid tumors that have spread and are not treatable by surgery or other standard treatments. Participants must have specific genetic mutations, including BRCA1/2, and their cancer must have progressed after previous PARP inhibitor treatment. They should be in good physical condition (ECOG score 0-1), able to undergo a biopsy, and willing to use effective contraception.

Inclusion Criteria

I am fully active or can carry out light work.

I have a genetic mutation in BRCA1 or BRCA2.

I have specific gene mutations related to DNA repair or cyclin E amplification.

My cancer initially responded to treatment but has since gotten worse.

I have BRCA mutations and my cancer progressed after PARP inhibitor treatment.

I had treatment with PARP inhibitors, showed improvement but then my cancer progressed. I also have specific genetic mutations or changes.

My tumor can be measured and biopsied, and I agree to have a biopsy.

My cancer has spread, cannot be surgically removed, and standard treatments are not effective.

I've had at least one treatment for my advanced cancer or there are no treatments known to work for me.

I am using two effective birth control methods or not having sex.

I am HIV-positive, on treatment, with no recent severe infections and a good immune status.

My cancer can be measured and biopsied safely, and I agree to have a biopsy.

My cancer has spread, cannot be surgically removed, and standard treatments are not effective.

I have been treated with PARP inhibitors before.

Exclusion Criteria

I have or had myelodysplastic syndrome or acute myeloid leukemia.

I am not taking strong or moderate drugs that affect liver enzymes.

I haven't had major surgery in the last 28 days or minor surgery in the last 7 days.

I am allergic to medications similar to AZD1775 or olaparib.

I am not taking any other cancer treatments while on the study medication.

I have brain metastases but they are stable and treated.

I have lasting side effects from cancer treatment, but not hair loss.

I haven't had serious heart issues like heart attacks or uncontrolled heart rhythm problems in the last 6 months.

I have not had radiotherapy in the last 28 days.

I haven't taken any cancer drugs in the last 28 days or 5 half-lives.

I cannot swallow pills or have a stomach condition that affects medication absorption.

I have had a bone marrow or cord blood transplant before.

I will not drink grapefruit juice while taking the study drugs.

Participant Groups

The STAR study is testing the sequential use of two anti-cancer drugs: Olaparib followed by Adavosertib in patients with advanced solid tumors resistant to PARP inhibitors. The goal is to find the safest doses with the least side effects while trying to shrink or stabilize the cancer.

1Treatment groups

Experimental Treatment

Group I: Treatment (olaparib, adavosertib)Experimental Treatment2 Interventions

Patients receive olaparib PO BID on days 1-5 and 15-19 of each cycle and adavosertib PO QD on days 8-12 and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.