InformationClinical trials have complex eligibility criteria.
Always talk to your clinician about you’re interest in participating in a trial.
Learn why

Optimise reading forHealth ProfessionalsPatients

Recruitment on holdLast updated: 2 February 2024

MoST 10 (substudies 23-24): This Phase II trial is evaluating how safe, tolerable and effective targeted therapy (palbociclib) is when combined with immunotherapy (avelumab) is in people with solid cancers with activating alterations in cell cycle genesSingle arm, open label, signal seeking, phase II trial of the activity of Palbociclib in combination with Avelumab in patients with tumours with amplified D-type cyclins or CDK4/6 or inactivation of CDKN2A.

Clinical summary

Summary

This is a substudy of the Cancer Molecular Screening and Therapeutics (MoST) Program (ACTRN12616000908437). This is an open-label trial for patients with solid cancers with amplified D-type cyclins or CDK4/5 or inactivation of CDKN2A. All participants will receive Palbociclib first on its own in the first cycle of treatment. Palbociclib will be administered orally at a dose of 125mg once daily for 21 days, followed by 7 days of washout. This dosage may be reduced if participants experiences intolerance toxicity. Avelumab will be administered intravenously at a dose of 10mg/kg every 2 weeks, starting from the second cycle of treatment. Both drugs will be administered continuously until disease progression is documented or when the participant experiences intolerable toxicity or withdraws for another reason.

Conditions

This trial is treating patients with solid cancers

Cancer

Multi-Cancer Multi-Cancer

Age

People18+

Phase

II

Trial Acronym

MoST 10 (substudies 23-24)

More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

University of Sydney,Australian Genomic Cancer Medicine Centre (AGCMC)

Scientific Title

Single arm, open label, signal seeking, phase II trial of the activity of Palbociclib in combination with Avelumab in patients with tumours with amplified D-type cyclins or CDK4/6 or inactivation of CDKN2A.

Eligibility

Inclusion

Inclusion Criteria – molecular screening:
1. Male or female patients, aged 18 years and older, with pathologically confirmed advanced and/or metastatic cancer of any histologic type, including haematological cancers, or an earlier diagnosis of a poor prognosis cancer;
2. Sufficient and accessible tissue for molecular screening;
3. Patients receiving their last line of standard treatment or who have received and failed all standard anticancer therapy (where standard therapy exists) or have documented unsuitability for any further standard anticancer therapy. Poor prognosis cancers or cancers with low expected response rate to standard treatment (in the opinion of the investigator and based on available evidence) may be screened on an earlier line of treatment.
a. Failure is defined as either progression of disease (clinical or radiological) or intolerance to standard therapy resulting in the discontinuation of the therapy.
b. Documented unsuitability for further standard therapy includes known hypersensitivity, organ dysfunction or other patient factors that would make therapy unsuitable in the judgement of the responsible investigator;
4. ECOG performance status 0, 1 or 2;
5. Willing and potentially able to comply with study requirements, including treatment, timing and/or nature of required assessments; It is the intention to screen patients who are in principle wishing to take part in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase;

It is the intention to screen patients who are in principle wishing to take part in a MoST substudy if they are found to have an appropriate tumour biomarker and are still eligible for enrolment at the time of the treatment phase (substudy).

To be eligible for treatment in a substudy, patients must continue to meet all of the inclusion criteria and none of the exclusion criteria specified for entry into molecular screening at the time of registration to a treatment substudy. In addition, they must meet all the inclusion criteria and none of the exclusion criteria in the substudy addendum at the time of registration.

Inclusion Criteria – substudy:
1. Confirmation of molecular eligibility by the molecular tumour board; Patients with tumour harbouring
a. Gain-of-function mutations in CDK4 or CCND1-3
b. CDKN2A deletion or loss-of-function mutations
2. Received and failed all standard anticancer therapy or have documented unsuitability for any further standard therapy, if standard therapy exists;
3. Clinical or radiological progression on or following last anticancer therapy unless such anticancer therapy stopped due to toxicity / treatment intolerance;
4. Adequate organ system function as assessed by the following minimal laboratory requirements (within 7 days prior to first administration of study drug):
a. bone marrow function; platelets equal or greater than 100 x 10^9/L, ANC equal or greater than 1.5 x 10^9/L, and haemoglobin equal or greater than 9g/dL (5.6mmol/L); This will not apply for patients with haematological cancers if cytopenias are disease related;
b. liver function; ALT/AST equal or less than 3 x ULN (in the absence of liver metastases, equal or less than 5 x ULN for patients with liver involvement) and total bilirubin equal or less than 1.5xULN;
c. renal function; serum creatinine equal or less than 1.5xULN;
5. Measurable disease by iRECIST and RECIST v 1.1 or RANO
6. Consent to have a fresh core biopsy at end of cycle 1 of study treatment
7. Life expectancy greater than or equal to 3 months
8. ECOG performance status 0 or 1

Exclusion

Exclusions criteria - molecular screening
1. Suitable for standard therapy or accepted standard care, if the patient has not been previously treated;
2. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may contraindicate participation and/or interact with the investigational product;
3. Other co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
4. For non central nervous system (CNS) cancers, patients with symptomatic CNS involvement of his/her cancer are excluded. Subjects with stable neurological function on stable doses of steroids/anti-epileptics over 4 weeks, and with no evidence of CNS progression within 12 weeks prior to screening are eligible;
5. History of another malignancy within 2 years prior to molecular screening registration are excluded unless adequately treated and determined free of progressive and metastatic disease for at least 6 months. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder can be included;
6. Pregnancy, lactation or inadequate contraception.

Exclusion criteria - substudy
1. Hormone positive breast cancer
2. Contraindications to investigational product;
3. Known history of hypersensitivity to active or inactive components of investigational product;
4. Prior treatment with CDK4/6 inhibitor or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
5. Prior treatment with checkpoint inhibitor
6. Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers, and drugs that are known to prolong the QT interval
7. QTc interval greater than 480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
8. Prolonged use of moderate to high doses of immunosuppressive medication before the first dose of avelumab. Exceptions include intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (eg. <=10 mg/day of prednisone; use of dexamethasone up to 4mg /day within 14 days of initial treatment for patients with brain tumours).
9. Receipt of any organ transplantation including allogeneic stem-cell transplantation.
10. Significant acute or chronic infections including, among others:
a. Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
b. Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
11. Active or history of any autoimmune disease (subjects with diabetes Type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible) or immunodeficiencies.
12. Currently diagnosed with interstitial lung disease or pneumonitis
13. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medications which may interact with the investigational product(s);
14. Co-morbidities or conditions that may compromise assessment of key outcomes or in the opinion of the clinician, limit the ability of the patient to comply with the protocol;
15. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment:
a. Radiation therapy, surgery or tumour embolization within 14 days prior to the first dose of study treatment. Palliative radiotherapy (for analgesia) is acceptable only if the irradiated field does not include target lesions;
b. Chemotherapy, biologic therapy, or hormonal therapy within 14 days or 5 half-lives of a drug prior to the first dose of study treatment or until recovery from previous therapy (whichever is longer);
16. Any unresolved toxicity ( greater than CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripheral neuropathy);
17. Administration of any investigational treatment within 30 days


Inclusion

  • You are able to swallow medication by mouth.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You have had treatment, but your cancer has come back.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

Participating hospitals

+ Show non-recruiting hospitals

On hold hospitals

Closed hospitals

InformationTell us if you find this trial availability is not accurate.Report inaccuracy

Get Support

Example

Cancer Connect

You might find it helpful to speak to someone who has 'been there before'. Our Cancer Connect program can provide one-on-one phone support from someone who understands what you're going through and has clinical trials experience.

Learn more

Example

Cancer Council’s cancer nurses

If you need cancer information and practical support for yourself, a carer, family or friend, contact Cancer Council’s experienced cancer nurses on 131120.

Learn more

Example

Information for family, friends and carers

When you are considering a cancer clinical trial, it is a good idea to discuss it with your family, friends or carers.

Learn more

Victorian Cancer Registry Victorian Government

The Victorian Cancer Trials Link is supported by the Victorian Government through the Victorian Cancer Agency.

RAP

Cancer Council Victoria would like to acknowledge the traditional custodians of the land on which we live and work. We would also like to pay respect to the elders past and present and extend that respect to all other Aboriginal people.